Risk Factors for Recurrent Tuberculosis among Patients on Anti-Retroviral Treatment in Rural Northeast South Africa: Findings from clinic records in the Agincourt sub-district

Risk Factors for Recurrent Tuberculosis among Patients on Anti-Retroviral Treatment in Rural Northeast South Africa: Findings from clinic records in the Agincourt sub-district | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Risk Factors for Recurrent Tuberculosis among Patients on Anti-Retroviral Treatment in Rural Northeast South Africa: Findings from clinic records in the Agincourt sub-district Kingsley Kanzoole, Chodziwadziwa Whiteson Kabudula, Juliana Kagura, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6442921/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Introduction Tuberculosis (TB) remains a major global health concern, particularly among HIV-infected individuals. Recurrent TB contributes significantly to the TB burden, especially in high-prevalence areas. In this study, we determined the incidence rate of recurrent TB and investigated the risk-factors for recurrence of TB among HIV-infected people on Anti-retroviral treatment in the rural Agincourt sub-district in Mpumalanga Province, South Africa. Methods A retrospective cohort study was conducted using clinic data linked to the Agincourt Health and Socio-Demographic Surveillance System (HDSS) from January 2014 to December 2022. Cox regression was used to determine risk factors for recurrent TB. Results Among 4,803 patients, 396 (8.2%) experienced recurrent TB, with a recurrence rate of 3.0 per 100 person-years. Time to recurrence ranged from 7 days to 8.66 years, with a median of 1.93 years. Significant risk factors included being male (aHR = 1.48, CI: 1.11–1.96), WHO HIV stage (aHR = 2.53, CI: 1.81–3.54), baseline CD4 count ≤ 185 cells/mm³ (aHR = 0.98, CI: 0.98–0.99), and prior TB treatment duration > 6 months (aHR = 0.96, CI: 0.93–0.98). Conclusion Findings highlight the need for targeted interventions for males, early HIV diagnosis, improved CD4 maintenance, and continuous TB monitoring during and post-treatment to reduce recurrence risk. Health sciences/Health care/Public health/Epidemiology Health sciences/Risk factors Recurrent tuberculosis Recurrence rate ART HIV Incidence rate Figures Figure 1 Figure 2 Background Tuberculosis (TB) is a chronic infectious disease caused by the bacterium Mycobacterium tuberculosis [ 1 ]. Although it mostly affects the lungs, it can also affect other organs such as the brain, kidneys, and bones [ 1 ]. According to the World Health Organisation (WHO), TB is one of the top 10 global causes of mortality, raising serious public health concerns [ 2 ]. In 2020, an estimated 10 million people were diagnosed with TB and 1.5 million died from the disease [ 2 ]. Recurrent tuberculosis (TB), which can result from endogenous reactivation of a pre-existing infection or exogenous reinfection by a new strain [ 1 , 3 ], is defined by the World Health Organization as another episode of TB disease among patients who were successfully treated and declared cured [ 1 ]. The US National Tuberculosis Surveillance System (NTSS) definition of Recurrent TB is slightly different in that it considers it as TB diagnosis that occurs twelve months or more after the last clinical encounter for anti-tuberculosis treatment, and any TB diagnosis that occurs sooner than twelve months is considered a continuation of the same episode and not counted as a new incident of TB [ 3 ]. Recurrent tuberculosis is a significant contributor to the overall TB burden worldwide, particularly in areas where TB prevalence is high [ 4 – 6 ], and among HIV infected people [ 6 – 8 ]. Previous research has shown a strong correlation between TB and HIV epidemics, as individuals with HIV have a higher risk of contracting TB again, making them more vulnerable to recurrent TB disease [ 7 , 9 – 11 ]. According to various studies, recurrent TB accounts for 5 to 30 percent of the global TB burden [ 4 , 6 , 8 , 9 ]. South Africa is one of the countries with a high burden of TB, accounting for three percent of cases worldwide [ 2 , 12 ]. According to Fischinger et al. (2021), the majority of TB cases in South Africa are recurrent cases, caused by relapse or reinfection [ 13 ]. Recent studies indicate that recurrent TB accounts for a significant proportion of the overall TB burden in the country, with estimates ranging from 8–20% of all TB cases [ 4 , 12 ]. The incidence of recurrent TB in South Africa is high, with one recent study in Cape town showing an incidence rate of 16.4 per 1000 person-years [ 4 ]. The significant burden of recurrent TB in South Africa emphasizes the urgent need for targeted interventions and strategies to address this issue. The high incidence of recurrent TB, particularly among individuals with HIV, poses challenges to TB control efforts and hinders progress in reducing the overall TB burden. We, therefore analysed clinic data linked to the Agincourt Health and socio-Demographic Surveillance System (HDSS) data to identify the risk factors associated with recurrent TB in the rural Agincourt sub-district in northeast, South Africa between January 2014 to December 2022. Results Characteristics of study participants A total of 4,802 participants were included in the analysis and their characteristics, including demographic and clinical data, are presented in Table 1. Among the study participants, 27.6% (n=1,326) were male, while 72.4% (n=3,476) were female. Weight of the patients ranged from 29 kgs to 165 kgs, with a median weight of 66 kgs and an interquartile range of 58.0 – 77.0 kgs. With respect to age, 24.8% (n=1,188) of the patients were between 18 to 29 years old, 34.5% (n=1,657) were aged between 30 to 39 years, 23.1% (n=1,110) fell in the 40 to 49 years age group, 11.0% (n=527) were between 50 to 59 years old, and 6.6% (n=319) were 60 years or older. In terms of WHO HIV staging, the majority (84.7%, n=3,186) were on stage one, while 7.6% (n=286) were on stage two, 7.0% (n=263) on stage three, and only 0.7% (n=28) on stage four. Additionally, 18.3% (n=881) had no comorbidities, while 81.7% (n=3,921) had comorbidities. The adherence rates to both TB and HIV medications were relatively high, with 91.4% (n=4,390) adherent to TB medication and 88.0% (n=4,227) adherent to HIV medication. Period prevalence of recurrent TB Out of the total participants, (8.2%) 396 experienced recurrent TB, while (91.8%) 4,407 did not. Among those with recurrent TB, 36.1% (143) were male, and 63.9% (253) were female. On the other hand, out of those without TB recurrence, 26.8% (1,183) were male, and 73.2% (3,224) were female. The median weight for those with recurrent TB was 63.0 kgs, with an interquartile range of 54.2 – 70.0 kgs. In contrast, those without TB recurrence had a median weight of 66.5 kgs, with an interquartile range of 58.0 – 77.3 kgs. In terms of age distribution, among those with recurrent TB, 24.5% (97) were between 18 to 29 years old, 37.1% (147) were between 30 to 39 years old, 24.0% (95) were between 40 to 49 years old, 9.1% (36) were between 50 to 59 years old, and 5.3% (21) were 60 years old and above. Among those without TB recurrence, 24.8% (1,092) were between 18 to 29 years old, 34.3% (1,510) were between 30 to 39 years old, 23.0% (1,015) were between 40 to 49 years old, 11.1% (491) were between 50 to 59 years old, and 6.8% (298) were 60 years old and above. Furthermore, 67.1% (204) of the recurrent TB cases were on stage one of the WHO HIV staging, 9.2% (28) on stage two, 21.7% (66) on stage three, and 2.0% (6) on stage four. In comparison, among those without TB recurrence, 86.2% (2,984) were on stage one, 7.5% (258) on stage two, 5.7% (197) on stage three, and 0.6% (22) on stage four. Among those with recurrent TB, 18.2% (72) had comorbidities, and 81.8% (324) had no comorbidities. On the other hand, among those without recurrent TB, 18.4% (809) had comorbidities, and 81.6% (3,597) had no comorbidities. Regarding medication adherence, 6.3% (25) of the recurrent TB patients were not adherent to their TB medication during their first TB episode, and 10.4% (41) were not adherent to their HIV medication. Among those without TB recurrence, 8.8% (387) were not adherent to their TB medication during their first TB episode, and 12.2% (534) were not adherent to their HIV medication. Table 1 : Characteristics of the study population for recurrent TB among HIV patients on ART Variables Totals Recurrent TB (N, %) No Recurrent TB (N, %) P-Value 4,802 (100) 396 (8.2) 4,406 (91.8) Sex Male Female 1,326 (27.6) 3,476 (72.4) 143 (36.1) 253 (63.9) 1,183 (26.8) 3,223 (73.2) <0.001 Weight (Kgs) Median, (IQR), (Range) (N=3,663) 66, (58 – 77), (29 – 165) (N=305) 63, (54.2 – 70), (34 – 160) (N=3,358) 66.5, (58 – 77.3), (29 – 165) <0.001 Participant’s Age (years) 18 – 29 30 – 39 40 – 49 50 – 59 60+ 1,188 (24.8) 1,657 (34.5) 1,110 (23.1) 527 (11.0) 319 (6.6) 97 (24.5) 147 (37.1) 95 (24.0) 36 (9.1) 21 (5.3) 1,091 (24.8) 1,510 (34.3) 1,015 (23.0) 491 (11.1) 298 (6.8) 0.467 WHO stage (HIV) Stage 1 Stage 2 Stage 3 Stage 4 3,186 (84.7) 286 (7.6) 263 (7.0) 28 (0.7) 204 (67.1) 28 (9.2) 66 (21.7) 6 (2.0) 2,982 (86.2) 258 (7.5) 197 (5.7) 22 (0.6) <0.001 CD4 Count (Cells/mm 3 ) Median, (IQR) (N=4,594) 229, (112 – 390) (N=386) 184.5, (76 – 321) (N=4,208) 235, (117 – 395) <0.001 Duration of previous TB treatment (Weeks) Median, (IQR) 31, (16 – 49) 21, (12 – 35) 32, (17 – 50) <0.001 Comorbidities Comorbidities No comorbidities 881 (18.3) 3,921 (81.7) 72 (18.2) 324 (81.8) 809 (18.4) 3,597 (81.6) 0.300 Adherence to TB medication Poor Good 412 (8.6) 4,390 (91.4) 25 (6.3) 371 (93.7) 387 (8.8) 4,019 (91.2) 0.093 Adherence to HIV medication Poor Good 575 (12.0) 4,227 (88.0) 41 (10.4) 355 (89.6) 534 (12.1) 3,872 (87.9) 0.300 Incidence rate of recurrent TB among HIV patients who were on ART Table 2 presents the incidence rates of recurrent tuberculosis among HIV patients who were receiving ART in the rural northeast, South Africa during the period from January 1, 2014, to December 31, 2022, stratified by various demographic and clinical characteristics. The number of HIV patients on ART followed up in this study was 4,802, and 396 recurrent cases were observed during the study period. The recurrence rate was 3.0 per 100 person years (py), (95% CI: 2.7 – 3.3). The total time at risk was 131.4 person years. There was a statistically significant difference in the recurrence rate of HIV patients on ART by the patient’s sex, WHO stage of HIV, and their adherence to TB medication during the previous episode of TB. Age of the patient, comorbidities, and poor adherence to HIV medication by the patient (during the previous episode of TB) were not statistically significantly different using the log-rank test. The recurrence rate was higher in men (4.3 per 100 person years (95% CI: 3.6 – 5.0)) than women (2.6 per 100 person years (95% CI: 2.3 – 2.9)). The recurrence rate was slightly higher among the people of ages between 40 – 49 years old, at 3.3 per 100 person years (95% CI: 2.7 – 4.0), followed by people aged between 30 – 39 years old, at 3.2 per 100 person years (95% CI: 2.8 – 3.9). Among those aged between 18 – 29 years old, the recurrence rate was 2.8 per 100 person years (95% CI: 2.3 – 3.4). Among people aged between 50 – 59 years old, the recurrence rate was 2.6 per 100 person years (95% CI: 1.9 – 3.6), and for those aged 60 years old and above, the recurrence rate was 2.6 per 100 person years (95% CI: 1.7 – 4.0). Patients who were on stage 4 and stage 3 of the WHO HIV staging had a higher recurrence rate, at 8.7 per 100 person years (95% CI: 3.9 – 19.4) and 8.4 per 100 person years (95% CI: 6.6 – 10.7) respectively, while the recurrence rate among those at stage 2 and stage 1 was at 3.1 per 100 person years (95% CI: 2.1 – 4.5) and 2.4 per 100 person years (95% CI: 2.1 – 2.8) respectively. The recurrence rate was higher in patients who had no comorbidities as compared to those with comorbidities; 3.1 per 100 person years (95% CI: 2.8 – 3.5) against 2.6 per 100 person years (95% CI: 2.1 – 3.3). Patients that were not adherent to their TB medication had a higher recurrence rate, at 3.8 per 100 person years (95% CI: 2.5 – 5.6) than those that were adherent to their TB medication, whose recurrence rate was at 2.8 per 100 person years (95% CI: 2.7 – 3.3). Among those that were not adherent to their HIV medication, the recurrence rate was at 3.3 per 100 person years (95% CI: 2.5 – 4.5), slightly higher than that of those who were adherent to their HIV medication, which was at 3.0 per 100 person years (95% CI: 2.7 – 3.3). Table 2 : Tuberculosis recurrent rates by various variables Factor Categories Number Recurrent cases Follow-up person years (py) x 100 Recurrence rate per 100 py (95% CI) Log rank test P-value Overall 4,802 396 131.4 3.0 (2.7 – 3.3) Sex Male Female 1,326 3,472 143 253 33.6 97.8 4.3 (3.6 – 5.0) 2.6 (2.3 – 2.9) <0.001 Age 18 – 29 30 – 39 40 – 49 50 – 59 60+ 1,188 1,657 1,110 527 319 97 147 95 36 21 34.3 46.1 29.1 14.0 8.0 2.8 (2.3 – 3.4) 3.2 (2.7 – 3.8) 3.3 (2.7 – 4.0) 2.6 (1.9 – 3.6) 2.6 (1.7 – 4.0) 0.55 WHO Stage (HIV) Stage 1 Stage 2 Stage 3 Stage 4 3,186 286 263 28 204 28 66 6 83.8 9.1 7.9 0.7 2.4 (2.1 – 2.8) 3.1 (2.1 – 4.5) 8.4 (6.6 – 10.7) 8.7 (3.9 – 19.4) <0.001 Comorbidities Comorbidities No comorbidities 881 3,921 72 324 27.4 104.1 2.6 (2.1 – 3.3) 3.1 (2.8 – 3.5) 0.09 Adherence to TB medication Poor Good 4,390 412 25 371 6.6 124.8 2.6 (2.1 – 3.3) 3.1 (2.8 – 3.5) 0.02 Adherence to HIV medication Poor Good 4,227 575 41 355 12.3 119.1 3.3 (2.5 – 4.5) 3.0 (2.7 – 3.3) 0.17 Risk factors for recurrent TB among HIV patients who are on ART Table 3 shows the results of the risk factors for recurrent TB among HIV patients in rural northeast, South Africa. In the univariable Cox proportional hazards regression analysis, the patient’s sex, weight, WHO stage of HIV, CD4 count at baseline, duration of previous TB treatment, and poor adherence to TB medication were found to be significant predictors of recurrence of TB. Male patients were 73% more likely to experience recurrent TB than female patients (HR=1.73, 95% CI: 1.41 – 2.12). Patients with increased weight were less likely to experience recurrent TB. For each five kilograms increase in weight of the patient, there was 9% decrease in the risk of recurrent TB (HR=0.91, 95% CI: 0.87 – 0.95). Patients who were at stage three of the WHO HIV stages were 3.29 times more likely to experience recurrent TB compared to those at stage one (HR=3.29, 95% CI: 2.49 – 4.34). Patients at stage four were 3.62 times more likely to experience recurrent TB as compared to those at stage one (HR=3.62, 95% CI: 1.61 – 8.16). Patients with a low CD4 count at baseline had a high likelihood for experiencing recurrent TB than those with a high CD4 count at baseline. For every 10 cells/mm3 increase in CD4 count at baseline, the hazard of recurrent TB decreased by 0.98 (HR=0.98, 95% CI: 0.98 – 0.99). Patients with a longer duration of TB treatment were at a higher risk of recurrence of TB as compared to those with a short duration of TB treatment. For every one month increase in the duration of TB treatment, the risk of recurrent TB increased by a factor of 0.96 (HR=0.96, 95% CI: 0.93 – 0.98). Patients who were not adherent to their TB medication were more likely to experience recurrent TB than those who were adherent to their TB medication. Those that were not adherent were 60% more likely to experience recurrent TB (HR=1.60, 95% CI: 1.07 – 2.40). The factors: patient’s age, comorbidities, and poor adherence to HIV medication were found not to be associated with the recurrence of TB among HIV patients who are on ART in rural northeast, South Africa. In the multivariable analysis, after adjusting for all other variables in the model, it was found that the factors that were associated with recurrence of TB among HIV patients on ART in the rural northeast, South Africa were: sex of the patient, WHO stage (HIV) of the patient, baseline CD4 count of the patient, and duration of previous TB treatment of the patient. Male patients were 48% more likely to experience recurrent TB as compared to female patients (HR=1.48, 95% CI: 1.12 – 1.96), while adjusting for other variables. Patients on stage three of the WHO stages of HIV staging were 2.53 time more likely to experience recurrent TB as compared to patients at stage two (AHR=2.53, 95% CI: 1.81 – 3.54), while adjusting for other variables. Patients with a low CD4 count at baseline were more likely to experience recurrent TB than patients with high CD4 count at baseline. For every 10 cells/mm3 increase in CD4 count at baseline, there was a 1% decrease in the likelihood for TB recurrence (AHR=0.99, 95% CI: 0.98 – 0.99). Patients who had a longer duration of TB treatment were found to be more likely to experience recurrent TB as compared to patients with a short duration of TB treatment. For each one month increase in the duration of TB treatment, the hazard of recurrent TB was 0.95 (AHR=0.95, 95% CI: 0.92 – 0.98), while adjusting for other variables. Patient’s age, weight, comorbidities, poor adherence to TB medication, and poor adherence to HIV medication were found to be not statistically significant factors associated with recurrence of TB, in the multivariate analysis. Table 3 : Risk factors associated with recurrent tuberculosis Variables Crude HR (95% CI) P-value Adjusted HR (95% CI) P-value Sex Female Male ref 1.73 (1.41 – 2.12) - <0.001 1.48 (1.12 – 1.96) 0.007 Weight (5kgs) 0.91 (0.87 – 0.95) <0.001 0.97 (0.92 – 1.02) 0.22 Age 18 – 29 30 – 39 40 – 49 50 – 59 60+ ref 1.14 (0.88 – 1.47) 1.19 (0.90 – 1.59) 0.93 (0.63 – 1.36) 0.96 (0.60 – 1.53) - 0.33 0.22 0.70 0.85 0.80 (0.58 – 1.10) 0.83 (0.57 – 1.23) 0.72 (0.42 – 1.24) 1.01 (0.54 – 1.88) 0.17 0.36 0.24 0.97 WHO stage (HIV) Stage 1 Stage 2 Stage 3 Stage 4 ref 1.17 (0.79 – 1.73) 3.29 (2.49 – 4.34) 3.62 (1.61 – 8.16) - 0.45 <0.001 <0.002 1.09 (0.71 – 1.68) 2.53 (1.81 – 3.54) 0.68 (0.09 – 4.98) 0.68 <0.001 0.71 CD4 Count (10 Cells/mm 3 ) 0.98 (0.98 – 0.99) <0.001 0.99 (0.98 – 0.99) <0.001 Duration of previous TB treatment (months) 0.96 (0.93 – 0.98) <0.001 0.95 (0.92 – 0.98) 0.001 Comorbidities No comorbidities Comorbidities ref 0.80 (0.62 – 1.03) - 0.09 0.73 (0.49 – 1.09) 0.13 Adherence to TB medication Good Poor ref 1.60 (1.07 – 2.40) 0.02 1.40 (0.76 – 2.60) 0.29 Adherence to HIV medication Good Poor ref 1.25 (0.91 – 1.73) - 0.17 1.38 (0.85 – 2.24) 0.19 A Forest plot showing Hazard Ratios of the Risk Factors for recurrent Tuberculosis Methods Study design This was a retrospective secondary analysis of clinical data of HIV patients receiving antiretroviral treatment in nine primary healthcare facilities in the Agincourt sub-district between 1st January 2014 and 31st December 2022. The data is linked to data from the Agincourt HDSS. Study setting The Agincourt HDSS study area comprises 31 villages in the Agincourt sub-district in rural northeast, South Africa with an estimated population of about 116,000 people [ 14 ]. The area is characterised by high unemployment, circular labour migration, and poor public infrastructure. The population of the area also has South Africa's second-highest HIV prevalence rate at 13.9% in 2022 [ 15 ]. Data and study population The data used in the analysis was collected as part of the Agincourt HDSS-Clinic-Hospital link research project. Trained data entry clerks working for the Agincourt HDSS-Clinic-Hospital link project enter into the project’s electronic database visit-level information from HIV patient files after every clinic visit [ 14 ]. Overall, 24,481 individuals were diagnosed and treated for HIV in the Agincourt HDSS study area between 1st January 2014 and 31st December 2022. 8,384 were diagnosed and treated for TB at least once during the study period. After cleaning the data and excluding those who did not meet the inclusion criteria, 4,802 individuals were identified for analysis in this study. Data analysis We utilized Stata 17 SE to clean and analyse the data. Descriptive statistics were produced for all variables. Frequencies and percentages were calculated and presented for each categorical variable. Tests for normality were conducted on continuous variables which included participants’ weight, CD4 count at baseline and duration of previous TB treatment. Median, and interquartile range (IQR) were calculated and presented when the data was found to be not normally distributed. The Cox regression model was fitted to investigate factors associated with the recurrence of TB in individuals over time, after successful treatment. The fitness of the cox regression model was investigated using the Cox-Snell residual plot. Discussion This study highlights the persistent burden of recurrent TB among HIV patients on ART, with an incidence rate consistent with findings from similar settings in Sub-Saharan Africa. For example, a study conducted in Malawi, reported similar findings [ 16 ]. While rates reported across studies vary, they underscore the ongoing challenge of managing TB recurrence in populations with high HIV prevalence. For example, a study in Cape Town, South Africa reported lower incidence rate than this study [ 4 ]. Differences in healthcare infrastructure, diagnostic tools, and study designs may explain the variation, emphasizing the need for context-specific strategies to address this public health issue. Gender differences in TB recurrence rates were evident, with males at a higher risk than females. This finding reflects broader disparities in health-seeking behaviours and access to care, as females have better health seeking behaviour than males [ 17 ], suggesting a need for targeted outreach to improve outcomes for male patients. Thus, addressing structural and behavioural barriers that hinder timely healthcare access among men is crucial for reducing this disparity. The study observed lower recurrence rates among patients with comorbidities compared to their counterparts. This could be because patients with comorbidities were subjected to special treatment care due to the other medical conditions. However, this requires further research to ascertain this phenomenon. This study found that patients at stage 3 of the WHO HIV staging were at a significantly higher risk of experiencing recurrent TB compared to those at stage one. Ausman Ahmed et. al. (2017) reported similar findings. In their study, it was found that being in WHO clinical stages III and IV (AHR 2.84, 95% CI 1.11–7.27; AHR 3.07, 95% CI 1.08–8.75, respectively) was associated with a high risk of TB recurrence [ 18 ]. This highlights the importance of early HIV diagnosis and effective management to prevent disease progression and reduce the risk of TB recurrence as delayed initiation of ART can lead to immune suppression, increasing vulnerability to TB recurrence [ 10 ]. The study observed that TB recurrence varied across age groups, with middle-aged individuals (30–49 years) showing the highest rates and a slightly higher risk for TB recurrence. Similar trends have been reported in other studies. For instance, a study in Bangui found that the highest TB recurrence rates were among the 25–34 age group [ 19 ].This pattern might be influenced by occupational exposures, healthcare access, or immune aging. These findings highlight the need for nuanced interventions tailored to specific age groups, ensuring comprehensive support for all patients. The current investigation demonstrated that individuals with a higher baseline CD4 count exhibited a reduced likelihood of experiencing TB recurrence. Similar findings were also reported by Lawn, Stephen D et. al. [ 20 ]. In their study, it was found that a CD4 count of less than 100cells/mm3 was associated with recurrent TB (ARR, 2.38; 95% CI, 1.01–5.60; P = 0.04) [ 20 ]. This crucial finding accentuates the pivotal role of maintaining a robust immune system, which can be achieved through early initiation of antiretroviral therapy and adherence to TB and HIV treatment, as pivotal strategies to mitigate the risk of TB recurrence in individuals living with HIV. Conclusion This study has identified several significant risk factors associated with recurrent TB among HIV patients receiving ART in the rural northeast South African setting. Male patients were found to be at a higher risk of experiencing recurrent TB compared to female patients, emphasizing the need for targeted interventions to address this gender disparity and improve TB outcomes among male individuals. Additionally, patients at more advanced stages of HIV (WHO stage three and stage four) were at a significantly higher risk of TB recurrence, highlighting the importance of early HIV diagnosis and effective management to prevent disease progression. Maintaining a higher baseline CD4 count was associated with a lower likelihood of TB recurrence, underscoring the importance of early initiation of ART and adherence to HIV treatment to reduce the risk of TB recurrence. Furthermore, patients with a longer duration of TB treatment were found to be at a higher risk of recurrence, indicating the need for continuous monitoring and support during and after TB treatment to prevent future recurrences. These findings can provide valuable insights for healthcare providers and policymakers in developing targeted strategies to mitigate the risk of recurrent TB and improve the overall health outcomes of HIV patients in this region. Further research and collaboration between healthcare professionals are crucial in addressing these risk factors effectively and achieving better control of recurrent TB among HIV patients. Declarations Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical Approval Statement Ethical approval for this study was obtained from the Human Research Ethics Committee (Medical) of the University of Witwatersrand, clearance certificate number: M230409 MED23-02-201. Permission to use Agincourt HDSS-Clinic-Link data was granted by MRC/Wits Rural Public Health and Health Transitions Research Unit. Due to the retrospective nature of the study, the Human Research Ethics Committee (Medical) of the University of Witwatersrand waived the need of obtaining informed consent. We confirm that all methods were carried out in accordance with relevant guidelines and regulations. Source of Funding The research work was supported by TDR, the Special Programme for Research and Training in Tropical Diseases, which is hosted at the World Health Organization and co-sponsored by UNICEF, UNDP, the World Bank and WHO. TDR grant number: B40299. First author ORCID ID: 0000-0003-1287-9430. Authors’ Contributions Kingsley Kanzoole (KK) conceived and designed the study, conducted data analysis, and led the manuscript writing. Chodziwadziwa Whiteson Kabudula (CWK) contributed to study design, data analysis, and provided critical revisions to the manuscript, and supervised the research process. Juliana Kagura (JK) assisted in manuscript writing and revisions. Tobias Chirwa (TC) critically reviewed the manuscript. Latifat Ibisomi (LI) contributed to study design, supervised the research process, and provided critical revisions to the manuscript. Data availability The data that support the findings of this study are available from (contact Dr Xavier Gómez-Olivé; [email protected] ). Details of application procedures with forms are available on the Agincourt data website (https://www.agincourt.co.za/1in10-dataset). References World Health Organization. Definitions and reporting framework for tuberculosis – 2013 revision (updated December 2014 and January 2020). World Health Organization; 2020. World Health Organization. Global tuberculosis report 2021. Geneva: World Health Organization; 2021. Cole B, Nilsen DM, Will L, Etkind SC, Burgos M, Chorba T. 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Increased recurrence of tuberculosis in HIV-1-infected patients in Kenya. Lancet 1993;7. https://doi.org/10.1016/0140-6736(93)91474-z. K. F. Mallory, G. J. Churchyard, I. Kleinschmidt, K. M. De Cock, E. L. Corbett. The impact of HIV infection on recurrence of tuberculosis in South African gold miners. The International Journal of Tuberculosis and Lung Disease 2000;4:455–62. Martie van der Walt, Sizulu Moyo. The First National TB Prevalence Survey South Africa. South Africa: South African Medical Research Council; 2018. Stephanie Fischinger, Deniz Cizmeci, Sally Shin, Leela Davies, Patricia S. Grace, Aida Sivro, et al. A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis. Front Immunol 2021;12. https://doi.org/10.3389/fimmu.2021.729186. Kathleen Kahn, Mark A Collinson, F Xavier Go ́mez-Olive ́, Obed Mokoena, Rhian Twine, Paul Mee, et al. Profile: Agincourt Health and Socio-demographic Surveillance System. International Journal Of Epidemiology 2012;41:988–1001. https://doi.org/10.1093/ije/dys115. The Provincial AIDS Council. The Mpumalanga Provincial Implementation Plan for HIV, TB and STIs for 2017 – 2022 n.d. Amelia C. Crampin, J. Nimrod Mwaungulu, Frank D. Mwaungulu, D. Totah Mwafulirwa, Kondwani Munthali, Sian Floyd, et al. Recurrent TB: relapse or reinfection? The effect of HIV in a general population cohort in Malawi. Europe PMC Funders Group 2010;24:417–26. https://doi.org/10.1097/QAD.0b013e32832f51cf. E. Johansson, N.H. Long, V.K. Diwan, A. Winkvist. Gender and tuberculosis control: Perspectives on health seeking behaviour among men and women in Vietnam. ELSEVIER 2000;52:33–51. https://doi.org/10.1016/S0168-8510(00)00062-2. Ausman Ahmed, Desalew Mekonnen, Atsede M Shiferaw, Fanuel Belayneh, Melaku K Yenit. Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study. BMJ n.d.;8. http://dx.doi.org/10.1136/bmjopen-2017-016961. Jean De Dieu Longo, Sylvain Honoré Woromogo, Henri Saint-Calvaire Diemer, Gaspard Tékpa, Laurent Belec, Gérard Grésenguet. Incidence and risk factors for tuberculosis among people living with HIV in Bangui: A cohort study. Public Health Pract (Oxf) 2022;4. https://doi.org/10.1016/j.puhip.2022.100302. Lawn, Stephen D, Badri, Motasim, Wood, Robin. Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort. AIDS 2005;19:2109–16. https://doi.org/10.1097/01.aids.0000194808.20035.c1. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6442921","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":495214380,"identity":"dd30078a-3533-4021-93bb-499c9c6916ff","order_by":0,"name":"Kingsley Kanzoole","email":"data:image/png;base64,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","orcid":"","institution":"University of the Witwatersrand","correspondingAuthor":true,"prefix":"","firstName":"Kingsley","middleName":"","lastName":"Kanzoole","suffix":""},{"id":495214381,"identity":"53b26d47-9f6c-4fc2-b64b-33846af0abe0","order_by":1,"name":"Chodziwadziwa Whiteson Kabudula","email":"","orcid":"","institution":"University of the Witwatersrand","correspondingAuthor":false,"prefix":"","firstName":"Chodziwadziwa","middleName":"Whiteson","lastName":"Kabudula","suffix":""},{"id":495214382,"identity":"2132814d-e4d8-4a50-acaf-82c1b501637f","order_by":2,"name":"Juliana Kagura","email":"","orcid":"","institution":"University of the Witwatersrand","correspondingAuthor":false,"prefix":"","firstName":"Juliana","middleName":"","lastName":"Kagura","suffix":""},{"id":495214383,"identity":"9b621605-f35f-4b5b-9831-a3fb4ea2dcaa","order_by":3,"name":"Tobias Chirwa","email":"","orcid":"","institution":"University of the Witwatersrand","correspondingAuthor":false,"prefix":"","firstName":"Tobias","middleName":"","lastName":"Chirwa","suffix":""},{"id":495214384,"identity":"a508bb84-578e-439d-98e4-b0bec6c5aae4","order_by":4,"name":"Latifat Ibisomi","email":"","orcid":"","institution":"University of the Witwatersrand","correspondingAuthor":false,"prefix":"","firstName":"Latifat","middleName":"","lastName":"Ibisomi","suffix":""}],"badges":[],"createdAt":"2025-04-14 06:23:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6442921/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6442921/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88643124,"identity":"e44dc0d5-e84c-4d2e-91d2-e5f627683673","added_by":"auto","created_at":"2025-08-08 16:14:32","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":567983,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA Forest plot showing Tuberculosis recurrent rates by various variables\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6442921/v1/7cd025ad87644d6964ae36fe.jpeg"},{"id":88643125,"identity":"70567ac0-40db-4185-a01b-0f48ee980b65","added_by":"auto","created_at":"2025-08-08 16:14:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":223678,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA Forest plot showing Hazard Ratios of the Risk Factors for recurrent Tuberculosis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6442921/v1/3d3bd42c0a11e5461551e6c6.png"},{"id":88647285,"identity":"8d4544c4-338f-451e-8d1e-d13a7ee2ac68","added_by":"auto","created_at":"2025-08-08 16:38:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1810009,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6442921/v1/fad644bf-8eac-4fa8-afb8-83a6fd9ddf38.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk Factors for Recurrent Tuberculosis among Patients on Anti-Retroviral Treatment in Rural Northeast South Africa: Findings from clinic records in the Agincourt sub-district","fulltext":[{"header":"Background","content":"\u003cp\u003eTuberculosis (TB) is a chronic infectious disease caused by the bacterium Mycobacterium tuberculosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although it mostly affects the lungs, it can also affect other organs such as the brain, kidneys, and bones [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. According to the World Health Organisation (WHO), TB is one of the top 10 global causes of mortality, raising serious public health concerns [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In 2020, an estimated 10\u0026nbsp;million people were diagnosed with TB and 1.5\u0026nbsp;million died from the disease [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecurrent tuberculosis (TB), which can result from endogenous reactivation of a pre-existing infection or exogenous reinfection by a new strain [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], is defined by the World Health Organization as another episode of TB disease among patients who were successfully treated and declared cured [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The US National Tuberculosis Surveillance System (NTSS) definition of Recurrent TB is slightly different in that it considers it as TB diagnosis that occurs twelve months or more after the last clinical encounter for anti-tuberculosis treatment, and any TB diagnosis that occurs sooner than twelve months is considered a continuation of the same episode and not counted as a new incident of TB [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecurrent tuberculosis is a significant contributor to the overall TB burden worldwide, particularly in areas where TB prevalence is high [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and among HIV infected people [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Previous research has shown a strong correlation between TB and HIV epidemics, as individuals with HIV have a higher risk of contracting TB again, making them more vulnerable to recurrent TB disease [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. According to various studies, recurrent TB accounts for 5 to 30 percent of the global TB burden [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSouth Africa is one of the countries with a high burden of TB, accounting for three percent of cases worldwide [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. According to Fischinger et al. (2021), the majority of TB cases in South Africa are recurrent cases, caused by relapse or reinfection [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Recent studies indicate that recurrent TB accounts for a significant proportion of the overall TB burden in the country, with estimates ranging from 8\u0026ndash;20% of all TB cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The incidence of recurrent TB in South Africa is high, with one recent study in Cape town showing an incidence rate of 16.4 per 1000 person-years [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe significant burden of recurrent TB in South Africa emphasizes the urgent need for targeted interventions and strategies to address this issue. The high incidence of recurrent TB, particularly among individuals with HIV, poses challenges to TB control efforts and hinders progress in reducing the overall TB burden. We, therefore analysed clinic data linked to the Agincourt Health and socio-Demographic Surveillance System (HDSS) data to identify the risk factors associated with recurrent TB in the rural Agincourt sub-district in northeast, South Africa between January 2014 to December 2022.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCharacteristics of study participants\u003c/p\u003e\n\u003cp\u003eA total of 4,802 participants were included in the analysis and their characteristics, including demographic and clinical data, are presented in Table 1. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the study participants, 27.6% (n=1,326) were male, while 72.4% (n=3,476) were female. Weight of the patients ranged from 29 kgs to 165 kgs, with a median weight of 66 kgs and an interquartile range of 58.0 \u0026ndash; 77.0 kgs. With respect to age, 24.8% (n=1,188) of the patients were between 18 to 29 years old, 34.5% (n=1,657) were aged between 30 to 39 years, 23.1% (n=1,110) fell in the 40 to 49 years age group, 11.0% (n=527) were between 50 to 59 years old, and 6.6% (n=319) were 60 years or older. In terms of WHO HIV staging, the majority (84.7%, n=3,186) were on stage one, while 7.6% (n=286) were on stage two, 7.0% (n=263) on stage three, and only 0.7% (n=28) on stage four. Additionally, 18.3% (n=881) had no comorbidities, while 81.7% (n=3,921) had comorbidities. The adherence rates to both TB and HIV medications were relatively high, with 91.4% (n=4,390) adherent to TB medication and 88.0% (n=4,227) adherent to HIV medication. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePeriod prevalence of recurrent TB\u003c/p\u003e\n\u003cp\u003eOut of the total participants, (8.2%) 396 experienced recurrent TB, while (91.8%) 4,407 did not. Among those with recurrent TB, 36.1% (143) were male, and 63.9% (253) were female. On the other hand, out of those without TB recurrence, 26.8% (1,183) were male, and 73.2% (3,224) were female. The median weight for those with recurrent TB was 63.0 kgs, with an interquartile range of 54.2 \u0026ndash; 70.0 kgs. In contrast, those without TB recurrence had a median weight of 66.5 kgs, with an interquartile range of 58.0 \u0026ndash; 77.3 kgs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn terms of age distribution, among those with recurrent TB, 24.5% (97) were between 18 to 29 years old, 37.1% (147) were between 30 to 39 years old, 24.0% (95) were between 40 to 49 years old, 9.1% (36) were between 50 to 59 years old, and 5.3% (21) were 60 years old and above. Among those without TB recurrence, 24.8% (1,092) were between 18 to 29 years old, 34.3% (1,510) were between 30 to 39 years old, 23.0% (1,015) were between 40 to 49 years old, 11.1% (491) were between 50 to 59 years old, and 6.8% (298) were 60 years old and above.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, 67.1% (204) of the recurrent TB cases were on stage one of the WHO HIV staging, 9.2% (28) on stage two, 21.7% (66) on stage three, and 2.0% (6) on stage four. In comparison, among those without TB recurrence, 86.2% (2,984) were on stage one, 7.5% (258) on stage two, 5.7% (197) on stage three, and 0.6% (22) on stage four.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong those with recurrent TB, 18.2% (72) had comorbidities, and 81.8% (324) had no comorbidities. On the other hand, among those without recurrent TB, 18.4% (809) had comorbidities, and 81.6% (3,597) had no comorbidities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding medication adherence, 6.3% (25) of the recurrent TB patients were not adherent to their TB medication during their first TB episode, and 10.4% (41) were not adherent to their HIV medication. Among those without TB recurrence, 8.8% (387) were not adherent to their TB medication during their first TB episode, and 12.2% (534) were not adherent to their HIV medication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e: Characteristics of the\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003estudy population for recurrent TB among HIV patients on ART\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotals\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrent TB (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Recurrent TB (N, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e4,802 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e396 (8.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e4,406 (91.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,326 (27.6)\u003c/p\u003e\n \u003cp\u003e3,476 (72.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e143 (36.1)\u003c/p\u003e\n \u003cp\u003e253 (63.9)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,183 (26.8)\u003c/p\u003e\n \u003cp\u003e3,223 (73.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eWeight (Kgs)\u003c/p\u003e\n \u003cp\u003eMedian, (IQR), (Range)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e(N=3,663)\u003c/p\u003e\n \u003cp\u003e66, (58 \u0026ndash; 77),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(29 \u0026ndash; 165)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(N=305)\u003c/p\u003e\n \u003cp\u003e63, (54.2 \u0026ndash; 70),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(34 \u0026ndash; 160)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e(N=3,358)\u003c/p\u003e\n \u003cp\u003e66.5, (58 \u0026ndash; 77.3),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(29 \u0026ndash; 165)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eParticipant\u0026rsquo;s Age (years)\u003c/p\u003e\n \u003cp\u003e18 \u0026ndash; 29\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 \u0026ndash; 39\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40 \u0026ndash; 49\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 \u0026ndash; 59\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60+\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,188 (24.8)\u003c/p\u003e\n \u003cp\u003e1,657 (34.5)\u003c/p\u003e\n \u003cp\u003e1,110 (23.1)\u003c/p\u003e\n \u003cp\u003e527 (11.0)\u003c/p\u003e\n \u003cp\u003e319 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e97 (24.5)\u003c/p\u003e\n \u003cp\u003e147 (37.1)\u003c/p\u003e\n \u003cp\u003e95 (24.0)\u003c/p\u003e\n \u003cp\u003e36 (9.1)\u003c/p\u003e\n \u003cp\u003e21 (5.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1,091 (24.8)\u003c/p\u003e\n \u003cp\u003e1,510 (34.3)\u003c/p\u003e\n \u003cp\u003e1,015 (23.0)\u003c/p\u003e\n \u003cp\u003e491 (11.1)\u003c/p\u003e\n \u003cp\u003e298 (6.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;0.467\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eWHO stage (HIV)\u003c/p\u003e\n \u003cp\u003eStage 1\u003c/p\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003eStage 3\u003c/p\u003e\n \u003cp\u003eStage 4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,186 (84.7)\u003c/p\u003e\n \u003cp\u003e286 (7.6)\u003c/p\u003e\n \u003cp\u003e263 (7.0)\u003c/p\u003e\n \u003cp\u003e28 (0.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e204 (67.1)\u003c/p\u003e\n \u003cp\u003e28 (9.2)\u003c/p\u003e\n \u003cp\u003e66 (21.7)\u003c/p\u003e\n \u003cp\u003e6 (2.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2,982 (86.2)\u003c/p\u003e\n \u003cp\u003e258 (7.5)\u003c/p\u003e\n \u003cp\u003e197 (5.7)\u003c/p\u003e\n \u003cp\u003e22 (0.6)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eCD4 Count (Cells/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003eMedian, (IQR)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e(N=4,594)\u003c/p\u003e\n \u003cp\u003e229, (112 \u0026ndash; 390)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e(N=386)\u003c/p\u003e\n \u003cp\u003e184.5, (76 \u0026ndash; 321)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e(N=4,208)\u003c/p\u003e\n \u003cp\u003e235, (117 \u0026ndash; 395)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eDuration of previous TB treatment (Weeks)\u003c/p\u003e\n \u003cp\u003eMedian, (IQR)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31, (16 \u0026ndash; 49)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21, (12 \u0026ndash; 35)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32, (17 \u0026ndash; 50)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eComorbidities\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003cp\u003eNo comorbidities\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e881 (18.3)\u003c/p\u003e\n \u003cp\u003e3,921 (81.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72 (18.2)\u003c/p\u003e\n \u003cp\u003e324 (81.8)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e809 (18.4)\u003c/p\u003e\n \u003cp\u003e3,597 (81.6)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;0.300\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAdherence to TB medication\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e412 (8.6)\u003c/p\u003e\n \u003cp\u003e4,390 (91.4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (6.3)\u003c/p\u003e\n \u003cp\u003e371 (93.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e387 (8.8)\u003c/p\u003e\n \u003cp\u003e4,019 (91.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAdherence to HIV medication\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e575 (12.0)\u003c/p\u003e\n \u003cp\u003e4,227 (88.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41 (10.4)\u003c/p\u003e\n \u003cp\u003e355 (89.6)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e534 (12.1)\u003c/p\u003e\n \u003cp\u003e3,872 (87.9)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;0.300\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIncidence rate of recurrent TB among HIV patients who were on ART\u003c/p\u003e\n\u003cp\u003eTable 2 presents the incidence rates of recurrent tuberculosis among HIV patients who were receiving ART in the rural northeast, South Africa during the period from January 1, 2014, to December 31, 2022, stratified by various demographic and clinical characteristics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe number of HIV patients on ART followed up in this study was 4,802, and 396 recurrent cases were observed during the study period. The recurrence rate was 3.0 per 100 person years (py), (95% CI: 2.7 \u0026ndash; 3.3). The total time at risk was 131.4 person years. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant difference in the recurrence rate of HIV patients on ART by the patient\u0026rsquo;s sex, WHO stage of HIV, and their adherence to TB medication during the previous episode of TB. Age of the patient, comorbidities, and poor adherence to HIV medication by the patient (during the previous episode of TB) were not statistically significantly different using the log-rank test. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe recurrence rate was higher in men (4.3 per 100 person years (95% CI: 3.6 \u0026ndash; 5.0)) than women (2.6 per 100 person years (95% CI: 2.3 \u0026ndash; 2.9)). The recurrence rate was slightly higher among the people of ages between 40 \u0026ndash; 49 years old, at 3.3 per 100 person years (95% CI: 2.7 \u0026ndash; 4.0), followed by people aged between 30 \u0026ndash; 39 years old, at 3.2 per 100 person years (95% CI: 2.8 \u0026ndash; 3.9). Among those aged between 18 \u0026ndash; 29 years old, the recurrence rate was 2.8 per 100 person years (95% CI: 2.3 \u0026ndash; 3.4). Among people aged between 50 \u0026ndash; 59 years old, the recurrence rate was 2.6 per 100 person years (95% CI: 1.9 \u0026ndash; 3.6), and for those aged 60 years old and above, the recurrence rate was 2.6 per 100 person years (95% CI: 1.7 \u0026ndash; 4.0). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients who were on stage 4 and stage 3 of the WHO HIV staging had a higher recurrence rate, at 8.7 per 100 person years (95% CI: 3.9 \u0026ndash; 19.4) \u0026nbsp;and 8.4 per 100 person years (95% CI: 6.6 \u0026ndash; 10.7) \u0026nbsp;respectively, while the recurrence rate among those at stage 2 and stage 1 was at 3.1 per 100 person years (95% CI: 2.1 \u0026ndash; 4.5) and 2.4 per 100 person years (95% CI: 2.1 \u0026ndash; 2.8) respectively. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe recurrence rate was higher in patients who had no comorbidities as compared to those with comorbidities; 3.1 per 100 person years (95% CI: 2.8 \u0026ndash; 3.5) against 2.6 per 100 person years (95% CI: 2.1 \u0026ndash; 3.3). Patients that were not adherent to their TB medication had a higher recurrence rate, at 3.8 per 100 person years (95% CI: 2.5 \u0026ndash; 5.6) than those that were adherent to their TB medication, whose recurrence rate was at 2.8 per 100 person years (95% CI: 2.7 \u0026ndash; 3.3). Among those that were not adherent to their HIV medication, the recurrence rate was at 3.3 per 100 person years (95% CI: 2.5 \u0026ndash; 4.5), slightly higher than that of those who were adherent to their HIV medication, which was at 3.0 per 100 person years (95% CI: 2.7 \u0026ndash; 3.3).\u0026nbsp;\u003c/p\u003e\n\u003cp id=\"_Toc141115489\"\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e: Tuberculosis recurrent rates by various variables\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\" class=\"fr-table-selection-hover\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategories\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrent cases\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up person years (py) x 100\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrence rate per 100 py \u0026nbsp;(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLog rank test P-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e4,802\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e131.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e3.0 (2.7 \u0026ndash; 3.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e1,326\u003c/p\u003e\n \u003cp\u003e3,472\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003cp\u003e253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e33.6\u003c/p\u003e\n \u003cp\u003e97.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e4.3 (3.6 \u0026ndash; 5.0)\u003c/p\u003e\n \u003cp\u003e2.6 (2.3 \u0026ndash; 2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 \u0026ndash; 29\u003c/p\u003e\n \u003cp\u003e30 \u0026ndash; 39\u003c/p\u003e\n \u003cp\u003e40 \u0026ndash; 49\u003c/p\u003e\n \u003cp\u003e50 \u0026ndash; 59\u003c/p\u003e\n \u003cp\u003e60+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1,188\u003c/p\u003e\n \u003cp\u003e1,657\u003c/p\u003e\n \u003cp\u003e1,110\u003c/p\u003e\n \u003cp\u003e527\u003c/p\u003e\n \u003cp\u003e319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34.3\u003c/p\u003e\n \u003cp\u003e46.1\u003c/p\u003e\n \u003cp\u003e29.1\u003c/p\u003e\n \u003cp\u003e14.0\u003c/p\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.8 (2.3 \u0026ndash; 3.4)\u003c/p\u003e\n \u003cp\u003e3.2 (2.7 \u0026ndash; 3.8)\u003c/p\u003e\n \u003cp\u003e3.3 (2.7 \u0026ndash; 4.0)\u003c/p\u003e\n \u003cp\u003e2.6 (1.9 \u0026ndash; 3.6)\u003c/p\u003e\n \u003cp\u003e2.6 (1.7 \u0026ndash; 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eWHO Stage (HIV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eStage 1\u003c/p\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003eStage 3\u003c/p\u003e\n \u003cp\u003eStage 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3,186\u003c/p\u003e\n \u003cp\u003e286\u003c/p\u003e\n \u003cp\u003e263\u003c/p\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e204\u003c/p\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e83.8\u003c/p\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003cp\u003e7.9\u003c/p\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.4 (2.1 \u0026ndash; 2.8)\u003c/p\u003e\n \u003cp\u003e3.1 (2.1 \u0026ndash; 4.5)\u003c/p\u003e\n \u003cp\u003e8.4 (6.6 \u0026ndash; 10.7)\u003c/p\u003e\n \u003cp\u003e8.7 (3.9 \u0026ndash; 19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003cp\u003eNo comorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e881\u003c/p\u003e\n \u003cp\u003e3,921\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003cp\u003e324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27.4\u003c/p\u003e\n \u003cp\u003e104.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.6 (2.1 \u0026ndash; 3.3)\u003c/p\u003e\n \u003cp\u003e3.1 (2.8 \u0026ndash; 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eAdherence to TB medication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4,390\u003c/p\u003e\n \u003cp\u003e412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003cp\u003e124.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.6 (2.1 \u0026ndash; 3.3)\u003c/p\u003e\n \u003cp\u003e3.1 (2.8 \u0026ndash; 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eAdherence to HIV medication\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4,227\u003c/p\u003e\n \u003cp\u003e575\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003cp\u003e355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003cp\u003e119.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.3 (2.5 \u0026ndash; 4.5)\u003c/p\u003e\n \u003cp\u003e3.0 (2.7 \u0026ndash; 3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eRisk factors for recurrent TB among HIV patients who are on ART\u003c/p\u003e\n\u003cp\u003eTable 3 shows the results of the risk factors for recurrent TB among HIV patients in rural northeast, South Africa. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the univariable Cox proportional hazards regression analysis, the patient\u0026rsquo;s sex, weight, WHO stage of HIV, CD4 count at baseline, duration of previous TB treatment, and poor adherence to TB medication were found to be significant predictors of recurrence of TB. Male patients were 73% more likely to experience recurrent TB than female patients (HR=1.73, 95% CI: 1.41 \u0026ndash; 2.12). Patients with increased weight were less likely to experience recurrent TB. \u0026nbsp; For each five kilograms increase in weight of the patient, there was 9% decrease in the risk of recurrent TB (HR=0.91, 95% CI: 0.87 \u0026ndash; 0.95).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients who were at stage three of the WHO HIV stages were 3.29 times more likely to experience recurrent TB compared to those at stage one (HR=3.29, 95% CI: 2.49 \u0026ndash; 4.34). Patients at stage four were 3.62 times more likely to experience recurrent TB as compared to those at stage one (HR=3.62, 95% CI: 1.61 \u0026ndash; 8.16). Patients with a low CD4 count at baseline had a high likelihood for experiencing recurrent TB than those with a high CD4 count at baseline. For every 10 cells/mm3 increase in CD4 count at baseline, the hazard of recurrent TB decreased by 0.98 (HR=0.98, 95% CI: 0.98 \u0026ndash; 0.99). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients with a longer duration of TB treatment were at a higher risk of recurrence of TB as compared to those with a short duration of TB treatment. For every one month increase in the duration of TB treatment, the risk of recurrent TB increased by a factor of 0.96 (HR=0.96, 95% CI: 0.93 \u0026ndash; 0.98). Patients who were not adherent to their TB medication were more likely to experience recurrent TB than those who were adherent to their TB medication. Those that were not adherent were 60% more likely to experience recurrent TB (HR=1.60, 95% CI: 1.07 \u0026ndash; 2.40).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe factors: patient\u0026rsquo;s age, comorbidities, and poor adherence to HIV medication were found not to be associated with the recurrence of TB among HIV patients who are on ART in rural northeast, South Africa. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the multivariable analysis, after adjusting for all other variables in the model, it was found that the factors that were associated with recurrence of TB among HIV patients on ART in the rural northeast, South Africa were: sex of the patient, WHO stage (HIV) of the patient, baseline CD4 count of the patient, and duration of previous TB treatment of the patient. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMale patients were 48% more likely to experience recurrent TB as compared to female patients (HR=1.48, 95% CI: 1.12 \u0026ndash; 1.96), while adjusting for other variables. Patients on stage three of the WHO stages of HIV staging were 2.53 time more likely to experience recurrent TB as compared to patients at stage two (AHR=2.53, 95% CI: 1.81 \u0026ndash; 3.54), while adjusting for other variables. Patients with a low CD4 count at baseline were more likely to experience recurrent TB than patients with high CD4 count at baseline. For every 10 cells/mm3 increase in CD4 count at baseline, there was a 1% decrease in the likelihood for TB recurrence (AHR=0.99, 95% CI: 0.98 \u0026ndash; 0.99).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients who had a longer duration of TB treatment were found to be more likely to experience recurrent TB as compared to patients with a short duration of TB treatment. For each one month increase in the duration of TB treatment, the hazard of recurrent TB was 0.95 (AHR=0.95, 95% CI: 0.92 \u0026ndash; 0.98), while adjusting for other variables. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient\u0026rsquo;s age, weight, comorbidities, poor adherence to TB medication, and poor adherence to HIV medication were found to be not statistically significant factors associated with recurrence of TB, in the multivariate analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e: Risk factors associated with recurrent tuberculosis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"728\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude HR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted HR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eSex\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003cp\u003e1.73 (1.41 \u0026ndash; 2.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.48 (1.12 \u0026ndash; 1.96)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eWeight (5kgs)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e0.91 (0.87 \u0026ndash; 0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.97 (0.92 \u0026ndash; 1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18 \u0026ndash; 29\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 \u0026ndash; 39\u003c/p\u003e\n \u003cp\u003e40 \u0026ndash; 49\u003c/p\u003e\n \u003cp\u003e50 \u0026ndash; 59\u003c/p\u003e\n \u003cp\u003e60+\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003cp\u003e1.14 (0.88 \u0026ndash; 1.47)\u003c/p\u003e\n \u003cp\u003e1.19 (0.90 \u0026ndash; 1.59)\u003c/p\u003e\n \u003cp\u003e0.93 (0.63 \u0026ndash; 1.36)\u003c/p\u003e\n \u003cp\u003e0.96 (0.60 \u0026ndash; 1.53)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.80 (0.58 \u0026ndash; 1.10)\u003c/p\u003e\n \u003cp\u003e0.83 (0.57 \u0026ndash; 1.23)\u003c/p\u003e\n \u003cp\u003e0.72 (0.42 \u0026ndash; 1.24)\u003c/p\u003e\n \u003cp\u003e1.01 (0.54 \u0026ndash; 1.88)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eWHO stage (HIV)\u003c/p\u003e\n \u003cp\u003eStage 1\u003c/p\u003e\n \u003cp\u003eStage 2\u003c/p\u003e\n \u003cp\u003eStage 3\u003c/p\u003e\n \u003cp\u003eStage 4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003cp\u003e1.17 (0.79 \u0026ndash; 1.73)\u003c/p\u003e\n \u003cp\u003e3.29 (2.49 \u0026ndash; 4.34)\u003c/p\u003e\n \u003cp\u003e3.62 (1.61 \u0026ndash; 8.16)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.002\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.09 (0.71 \u0026ndash; 1.68)\u003c/p\u003e\n \u003cp\u003e2.53 (1.81 \u0026ndash; 3.54)\u003c/p\u003e\n \u003cp\u003e0.68 (0.09 \u0026ndash; 4.98)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eCD4 Count (10 Cells/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e0.98 (0.98 \u0026ndash; 0.99)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.99 (0.98 \u0026ndash; 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eDuration of previous TB treatment (months)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e0.96 (0.93 \u0026ndash; 0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.95 (0.92 \u0026ndash; 0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003cp\u003eNo comorbidities\u003c/p\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003cp\u003e0.80 (0.62 \u0026ndash; 1.03)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.73 (0.49 \u0026ndash; 1.09)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAdherence to TB medication\u003c/p\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003cp\u003e1.60 (1.07 \u0026ndash; 2.40)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.40 (0.76 \u0026ndash; 2.60)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 180px;\"\u003e\n \u003cp\u003eAdherence to HIV medication\u003c/p\u003e\n \u003cp\u003eGood\u003c/p\u003e\n \u003cp\u003ePoor\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003cp\u003e1.25 (0.91 \u0026ndash; 1.73)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.38 (0.85 \u0026ndash; 2.24)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA Forest plot showing Hazard Ratios of the Risk Factors for recurrent Tuberculosis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eThis was a retrospective secondary analysis of clinical data of HIV patients receiving antiretroviral treatment in nine primary healthcare facilities in the Agincourt sub-district between 1st January 2014 and 31st December 2022. The data is linked to data from the Agincourt HDSS.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eStudy setting\u003c/h2\u003e\u003cp\u003eThe Agincourt HDSS study area comprises 31 villages in the Agincourt sub-district in rural northeast, South Africa with an estimated population of about 116,000 people [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The area is characterised by high unemployment, circular labour migration, and poor public infrastructure. The population of the area also has South Africa's second-highest HIV prevalence rate at 13.9% in 2022 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eData and study population\u003c/h2\u003e\u003cp\u003eThe data used in the analysis was collected as part of the Agincourt HDSS-Clinic-Hospital link research project. Trained data entry clerks working for the Agincourt HDSS-Clinic-Hospital link project enter into the project\u0026rsquo;s electronic database visit-level information from HIV patient files after every clinic visit [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOverall, 24,481 individuals were diagnosed and treated for HIV in the Agincourt HDSS study area between 1st January 2014 and 31st December 2022. 8,384 were diagnosed and treated for TB at least once during the study period. After cleaning the data and excluding those who did not meet the inclusion criteria, 4,802 individuals were identified for analysis in this study.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eData analysis\u003c/h2\u003e\u003cp\u003eWe utilized Stata 17 SE to clean and analyse the data. Descriptive statistics were produced for all variables. Frequencies and percentages were calculated and presented for each categorical variable. Tests for normality were conducted on continuous variables which included participants\u0026rsquo; weight, CD4 count at baseline and duration of previous TB treatment. Median, and interquartile range (IQR) were calculated and presented when the data was found to be not normally distributed.\u003c/p\u003e\u003cp\u003eThe Cox regression model was fitted to investigate factors associated with the recurrence of TB in individuals over time, after successful treatment. The fitness of the cox regression model was investigated using the Cox-Snell residual plot.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study highlights the persistent burden of recurrent TB among HIV patients on ART, with an incidence rate consistent with findings from similar settings in Sub-Saharan Africa. For example, a study conducted in Malawi, reported similar findings [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. While rates reported across studies vary, they underscore the ongoing challenge of managing TB recurrence in populations with high HIV prevalence. For example, a study in Cape Town, South Africa reported lower incidence rate than this study [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Differences in healthcare infrastructure, diagnostic tools, and study designs may explain the variation, emphasizing the need for context-specific strategies to address this public health issue.\u003c/p\u003e\u003cp\u003eGender differences in TB recurrence rates were evident, with males at a higher risk than females. This finding reflects broader disparities in health-seeking behaviours and access to care, as females have better health seeking behaviour than males [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], suggesting a need for targeted outreach to improve outcomes for male patients. Thus, addressing structural and behavioural barriers that hinder timely healthcare access among men is crucial for reducing this disparity.\u003c/p\u003e\u003cp\u003eThe study observed lower recurrence rates among patients with comorbidities compared to their counterparts. This could be because patients with comorbidities were subjected to special treatment care due to the other medical conditions. However, this requires further research to ascertain this phenomenon.\u003c/p\u003e\u003cp\u003eThis study found that patients at stage 3 of the WHO HIV staging were at a significantly higher risk of experiencing recurrent TB compared to those at stage one. Ausman Ahmed et. al. (2017) reported similar findings. In their study, it was found that being in WHO clinical stages III and IV (AHR 2.84, 95% CI 1.11\u0026ndash;7.27; AHR 3.07, 95% CI 1.08\u0026ndash;8.75, respectively) was associated with a high risk of TB recurrence [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This highlights the importance of early HIV diagnosis and effective management to prevent disease progression and reduce the risk of TB recurrence as delayed initiation of ART can lead to immune suppression, increasing vulnerability to TB recurrence [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe study observed that TB recurrence varied across age groups, with middle-aged individuals (30\u0026ndash;49 years) showing the highest rates and a slightly higher risk for TB recurrence. Similar trends have been reported in other studies. For instance, a study in Bangui found that the highest TB recurrence rates were among the 25\u0026ndash;34 age group [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].This pattern might be influenced by occupational exposures, healthcare access, or immune aging. These findings highlight the need for nuanced interventions tailored to specific age groups, ensuring comprehensive support for all patients.\u003c/p\u003e\u003cp\u003eThe current investigation demonstrated that individuals with a higher baseline CD4 count exhibited a reduced likelihood of experiencing TB recurrence. Similar findings were also reported by Lawn, Stephen D et. al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In their study, it was found that a CD4 count of less than 100cells/mm3 was associated with recurrent TB (ARR, 2.38; 95% CI, 1.01\u0026ndash;5.60; P\u0026thinsp;=\u0026thinsp;0.04) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This crucial finding accentuates the pivotal role of maintaining a robust immune system, which can be achieved through early initiation of antiretroviral therapy and adherence to TB and HIV treatment, as pivotal strategies to mitigate the risk of TB recurrence in individuals living with HIV.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study has identified several significant risk factors associated with recurrent TB among HIV patients receiving ART in the rural northeast South African setting. Male patients were found to be at a higher risk of experiencing recurrent TB compared to female patients, emphasizing the need for targeted interventions to address this gender disparity and improve TB outcomes among male individuals. Additionally, patients at more advanced stages of HIV (WHO stage three and stage four) were at a significantly higher risk of TB recurrence, highlighting the importance of early HIV diagnosis and effective management to prevent disease progression. Maintaining a higher baseline CD4 count was associated with a lower likelihood of TB recurrence, underscoring the importance of early initiation of ART and adherence to HIV treatment to reduce the risk of TB recurrence. Furthermore, patients with a longer duration of TB treatment were found to be at a higher risk of recurrence, indicating the need for continuous monitoring and support during and after TB treatment to prevent future recurrences. These findings can provide valuable insights for healthcare providers and policymakers in developing targeted strategies to mitigate the risk of recurrent TB and improve the overall health outcomes of HIV patients in this region. Further research and collaboration between healthcare professionals are crucial in addressing these risk factors effectively and achieving better control of recurrent TB among HIV patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was obtained from the Human Research Ethics Committee (Medical) of the University of Witwatersrand, clearance certificate number: M230409 MED23-02-201. Permission to use Agincourt HDSS-Clinic-Link data was granted by MRC/Wits Rural Public Health and Health Transitions Research Unit. Due to the retrospective nature of the study, the Human Research Ethics Committee (Medical) of the University of Witwatersrand waived the need of obtaining informed consent. We confirm that all methods were carried out in accordance with relevant guidelines and regulations.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource of Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research work was supported by TDR, the Special Programme for Research and Training in Tropical Diseases, which is hosted at the World Health Organization and co-sponsored by UNICEF, UNDP, the World Bank and WHO. TDR grant number: B40299. First author ORCID ID: 0000-0003-1287-9430.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKingsley Kanzoole (KK) conceived and designed the study, conducted data analysis, and led the manuscript writing. Chodziwadziwa Whiteson Kabudula (CWK) contributed to study design, data analysis, and provided critical revisions to the manuscript, and supervised the research process. Juliana Kagura (JK) assisted in manuscript writing and revisions. Tobias Chirwa (TC) critically reviewed the manuscript. Latifat Ibisomi (LI) contributed to study design, supervised the research process, and provided critical revisions to the manuscript.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from (contact Dr Xavier G\u0026oacute;mez-Oliv\u0026eacute;; [email protected]). Details of application procedures with forms are available on the Agincourt data website (https://www.agincourt.co.za/1in10-dataset).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. Definitions and reporting framework for tuberculosis \u0026ndash; 2013 revision (updated December 2014 and January 2020). World Health Organization; 2020.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Global tuberculosis report 2021. Geneva: World Health Organization; 2021.\u003c/li\u003e\n\u003cli\u003eCole B, Nilsen DM, Will L, Etkind SC, Burgos M, Chorba T. Essential Components of a Public Health Tuberculosis Prevention, Control, and Elimination Program: Recommendations of the Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association. U.S. Department of Health and Human Services, Atlanta, GA 30329-4027: Centers for Disease Control and Prevention; 2020.\u003c/li\u003e\n\u003cli\u003eSabine M. Hermans, Nesbert Zinyakatira, Judy Caldwell, Frank G. J. Cobelens, Andrew Boulle, Robin Wood. High Rates of Recurrent Tuberculosis Disease: A Population-level Cohort Study. IDSA 2021;11:1919\u0026ndash;26. https://doi.org/10.1093/cid/ciaa470.\u003c/li\u003e\n\u003cli\u003ePatrick George Tobias Cudahy, Douglas Wilson, Ted Cohen. Risk factors for recurrent tuberculosis after successful treatment in a high burden setting: a cohort study. BMC Infectious Diseases 2020;20. https://doi.org/10.1186/s12879-020-05515-4.\u003c/li\u003e\n\u003cli\u003eVictor Vega, Sharon Rodr\u0026iacute;guez, Patrick Van der Stuyft, Carlos Seas, Larissa Otero. Recurrent TB: a systematic review and meta-analysis of the incidence rates and the proportions of relapses and reinfections. HHS Public Access 2021;76:494\u0026ndash;502. https://doi.org/doi: 10.1136/thoraxjnl-2020-215449.\u003c/li\u003e\n\u003cli\u003eP Sonnenberg, J Murray, J R Glynn, S Shearer, B Kambashi, P Godfrey-Faussett. HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South African mineworkers. Lancet 2002;358:1687\u0026ndash;93. https://doi.org/10.1016/S0140-6736(01)06712-5.\u003c/li\u003e\n\u003cli\u003eNaidoo, K, Dookie, N. Insights into Recurrent Tuberculosis: Relapse Versus Reinfection and Related Risk Factors. London: IntechOpen; 2018.\u003c/li\u003e\n\u003cli\u003eYoshan Moodley, Kumeren Govender. A systematic review of published literature describing factors associated with tuberculosis recurrence in people living with HIV in Africa. Afr Health Sci 2015;15:1239\u0026ndash;46. https://doi.org/10.4314/ahs.v15i4.24.\u003c/li\u003e\n\u003cli\u003eHawken M, Nunn P, Gathua S, Brindle R, P Godfrey-Faussett, Githui W, et al. Increased recurrence of tuberculosis in HIV-1-infected patients in Kenya. Lancet 1993;7. https://doi.org/10.1016/0140-6736(93)91474-z.\u003c/li\u003e\n\u003cli\u003eK. F. Mallory, G. J. Churchyard, I. Kleinschmidt, K. M. De Cock, E. L. Corbett. The impact of HIV infection on recurrence of tuberculosis in South African gold miners. The International Journal of Tuberculosis and Lung Disease 2000;4:455\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eMartie van der Walt, Sizulu Moyo. The First National TB Prevalence Survey South Africa. South Africa: South African Medical Research Council; 2018.\u003c/li\u003e\n\u003cli\u003eStephanie Fischinger, Deniz Cizmeci, Sally Shin, Leela Davies, Patricia S. Grace, Aida Sivro, et al. A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis. Front Immunol 2021;12. https://doi.org/10.3389/fimmu.2021.729186.\u003c/li\u003e\n\u003cli\u003eKathleen Kahn, Mark A Collinson, F Xavier Go ́mez-Olive ́, Obed Mokoena, Rhian Twine, Paul Mee, et al. Profile: Agincourt Health and Socio-demographic Surveillance System. International Journal Of Epidemiology 2012;41:988\u0026ndash;1001. https://doi.org/10.1093/ije/dys115.\u003c/li\u003e\n\u003cli\u003eThe Provincial AIDS Council. The Mpumalanga Provincial Implementation Plan for HIV, TB and STIs for 2017 \u0026ndash; 2022 n.d.\u003c/li\u003e\n\u003cli\u003eAmelia C. Crampin, J. Nimrod Mwaungulu, Frank D. Mwaungulu, D. Totah Mwafulirwa, Kondwani Munthali, Sian Floyd, et al. Recurrent TB: relapse or reinfection? The effect of HIV in a general population cohort in Malawi. Europe PMC Funders Group 2010;24:417\u0026ndash;26. https://doi.org/10.1097/QAD.0b013e32832f51cf.\u003c/li\u003e\n\u003cli\u003eE. Johansson, N.H. Long, V.K. Diwan, A. Winkvist. Gender and tuberculosis control: Perspectives on health seeking behaviour among men and women in Vietnam. ELSEVIER 2000;52:33\u0026ndash;51. https://doi.org/10.1016/S0168-8510(00)00062-2.\u003c/li\u003e\n\u003cli\u003eAusman Ahmed, Desalew Mekonnen, Atsede M Shiferaw, Fanuel Belayneh, Melaku K Yenit. Incidence and determinants of tuberculosis infection among adult patients with HIV attending HIV care in north-east Ethiopia: a retrospective cohort study. BMJ n.d.;8. http://dx.doi.org/10.1136/bmjopen-2017-016961.\u003c/li\u003e\n\u003cli\u003eJean De Dieu Longo, Sylvain Honor\u0026eacute; Woromogo, Henri Saint-Calvaire Diemer, Gaspard T\u0026eacute;kpa, Laurent Belec, G\u0026eacute;rard Gr\u0026eacute;senguet. Incidence and risk factors for tuberculosis among people living with HIV in Bangui: A cohort study. Public Health Pract (Oxf) 2022;4. https://doi.org/10.1016/j.puhip.2022.100302.\u003c/li\u003e\n\u003cli\u003eLawn, Stephen D, Badri, Motasim, Wood, Robin. Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort. AIDS 2005;19:2109\u0026ndash;16. https://doi.org/10.1097/01.aids.0000194808.20035.c1.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Recurrent tuberculosis, Recurrence rate, ART, HIV, Incidence rate","lastPublishedDoi":"10.21203/rs.3.rs-6442921/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6442921/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e\u003cp\u003eTuberculosis (TB) remains a major global health concern, particularly among HIV-infected individuals. Recurrent TB contributes significantly to the TB burden, especially in high-prevalence areas. In this study, we determined the incidence rate of recurrent TB and investigated the risk-factors for recurrence of TB among HIV-infected people on Anti-retroviral treatment in the rural Agincourt sub-district in Mpumalanga Province, South Africa.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective cohort study was conducted using clinic data linked to the Agincourt Health and Socio-Demographic Surveillance System (HDSS) from January 2014 to December 2022. Cox regression was used to determine risk factors for recurrent TB.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong 4,803 patients, 396 (8.2%) experienced recurrent TB, with a recurrence rate of 3.0 per 100 person-years. Time to recurrence ranged from 7 days to 8.66 years, with a median of 1.93 years. Significant risk factors included being male (aHR\u0026thinsp;=\u0026thinsp;1.48, CI: 1.11\u0026ndash;1.96), WHO HIV stage (aHR\u0026thinsp;=\u0026thinsp;2.53, CI: 1.81\u0026ndash;3.54), baseline CD4 count\u0026thinsp;\u0026le;\u0026thinsp;185 cells/mm\u0026sup3; (aHR\u0026thinsp;=\u0026thinsp;0.98, CI: 0.98\u0026ndash;0.99), and prior TB treatment duration\u0026thinsp;\u0026gt;\u0026thinsp;6 months (aHR\u0026thinsp;=\u0026thinsp;0.96, CI: 0.93\u0026ndash;0.98).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eFindings highlight the need for targeted interventions for males, early HIV diagnosis, improved CD4 maintenance, and continuous TB monitoring during and post-treatment to reduce recurrence risk.\u003c/p\u003e","manuscriptTitle":"Risk Factors for Recurrent Tuberculosis among Patients on Anti-Retroviral Treatment in Rural Northeast South Africa: Findings from clinic records in the Agincourt sub-district","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-08 16:14:27","doi":"10.21203/rs.3.rs-6442921/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-09-16T15:27:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126806411950453018979970930358343903799","date":"2025-09-11T13:57:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256938657666446848989402908822813487952","date":"2025-08-09T15:27:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15592253371988184128949806348542948424","date":"2025-08-04T07:59:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-04T07:44:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-29T08:45:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-23T05:42:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-22T10:18:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-04-14T06:17:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d3730ec5-1651-4dce-bf23-327b01a6b42d","owner":[],"postedDate":"August 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":52586762,"name":"Health sciences/Health care/Public health/Epidemiology"},{"id":52586763,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2025-08-08T16:14:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-08 16:14:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6442921","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6442921","identity":"rs-6442921","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}