Virological Outcomes and Dolutegravir Resistance Mutations in HIV-infected Patients: A Multicenter Retrospective Cohort Study in Mozambique

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Dolutegravir (DTG) has become a cornerstone of antiretroviral therapy (ART) regimens due to its efficacy and tolerability. However, the emergence of DTG resistance is a concern. This study aims to evaluate virological outcomes and the emergence of resistance mutations in patients treated with DTG in Mozambique. Methods A retrospective cohort study was conducted in seven DREAM centers in Mozambique. Data were collected from electronic medical records of patients on DTG-based ART between July-2022 and December-2023. Virological suppression rates, patient demographics and clinical characteristics, and the prevalence of resistance mutations were analyzed. Results A total of 29,601 patients were included, 98.1% (29,051 patients) were on DTG-based ART. The overall virological suppression rate among patients on DTG was 95% (27,622/29,051). Multivariate logistic regression analysis identified the following factors independently associated with virological suppression: older patients (aged > 50 years) had higher odds of achieving virological suppression (OR: 2.45, 95% CI: 1.85–3.26, p 5 years) was also associated with suppression (OR: 1.92, 95% CI: 1.44–2.58, p < 0.001), female patients had higher odds of suppression (OR: 0.85, 95% CI: 0.75–0.97, p = 0.02), and patients treated in Quelimane City had lower odds of suppression compared to those in Machava (OR: 0.67, 95% CI: 0.52–0.86, p = 0.01). Of the 74 samples sent for resistance testing, 17 were analyzed for DTG resistance, and 8 displayed resistance major mutations. The most common mutations identified were G118R and E138K, variably associated with other major mutations. Conclusions This study demonstrates the effectiveness of DTG within the DREAM program in Mozambique, with a high rate of virological suppression. However, the emergence of resistance mutations underscores the need for ongoing monitoring and surveillance to optimize treatment outcomes and preserve the efficacy of DTG. HIV Drug Resistance Viral HIV Integrase Inhibitors Antiretroviral Therapy Highly Active Africa Public Health Surveillance Figures Figure 1 INTRODUCTION The global HIV epidemic remains one of the most significant public health challenges, with an estimated 39.9 million people living with HIV worldwide as of 2023 [ 1 ]. The introduction of antiretroviral therapy (ART) has been crucial in reducing morbidity and mortality associated with HIV [ 2 ]. Among the various classes of ART drugs, integrase strand transfer inhibitors (INSTIs) have become a cornerstone in HIV treatment due to their high efficacy, good tolerability, and limited drug interactions [ 3 ]. Dolutegravir (DTG), a second-generation INSTI, has emerged as a preferred option in first-line ART regimens for its ability to achieve rapid and sustained viral suppression; in 2018, the World Health Organization (WHO) endorsed DTG as part of the preferred ART regimens, particularly in low- and middle-income countries, where the burden of HIV is disproportionately high [ 4 ]. WHO reports that up to now 91% of 127 reporting countries have adopted Dolutegravir (DTG)-based ART as the preferred first-line treatment for adults and adolescents; additionally, 77% of 116 countries have incorporated DTG into second-line therapy, and 69% of 114 countries prioritize DTG-based regimens for infants and children​ [ 5 ]. Mozambique is one of the countries most affected by the HIV epidemic, with approximately 2.4 million people living with the virus, according to the most recent UNAIDS estimates ​ [ 6 ]. According to UNAIDS, in 2023 Mozambique had achieved ART coverage for about 87.5% of people living with HIV (PLWH)​ [ 6 ]. DTG has been a key part of Mozambique’s national HIV treatment strategy since its introduction into first-line ART regimens in 2019 [ 7 ]. Although DTG has proven highly effective in managing HIV, the emergence of resistance remains a growing concern, especially in resource-limited settings​ [ 5 ]. Recent studies from the field have reported higher-than-expected rates of DTG resistance, particularly in populations with previous exposure to antiretroviral therapy, highlighting challenges in real-world implementation [ 8 , 9 ]. The most commonly identified mutations associated with DTG resistance in Sub-Saharan Africa, include G118R, E138K, all of which compromise at different levels the drug’s efficacy, posing a significant threat to the effectiveness of DTG-based regimens in the continent, where the HIV burden is highest [ 10 ]. In Mozambique, where access to advanced diagnostic tools is often limited, data on drug resistance are sparse. The primary objective of this study is to evaluate the prevalence of viral suppression among patients on DTG and to assess the emergence of drug resistance. In doing so, it aims to identify key factors that may contribute to treatment failure, such as prior ART exposure, and time on treatment. A secondary objective is to report data on mutations detected in the small number of patients who were able to access resistance testing. METHODS Study Design We conducted a multicenter retrospective cohort study to evaluate virological outcomes in patients on DTG-based regimens. By reviewing historical data, we assessed the prevalence of virological suppression, and the emergence of DTG resistance during the study period. We also compared virologically suppressed patients with those who were not suppressed, allowing for a more comprehensive evaluation of the real-world effectiveness of DTG in Mozambique. Setting The study was conducted across seven DREAM program centers located in different regions of Mozambique. These include three centers in Maputo City (Maputo City, Machava, and Zimpeto), which provide services to the southern region of the country. Additionally, Matola 2, situated in Maputo Province, serves the peri-urban area surrounding the capital. In the central region, two centers in Beira (Mangachingussura and Beira City) offer comprehensive healthcare services, particularly for urban and semi-urban populations. Finally, Quelimane City, located in the Zambezia Province, extends coverage to the northern part of Mozambique, ensuring a diverse and geographically representative patient population. These centers provide community-based healthcare with a focus on HIV treatment and ART [ 11 ]. The selection of these centers ensured a diverse and representative sample of PLWH receiving DTG treatment, encompassing a range of geographic and demographic profiles. Data Sources Data for this study were derived from electronic medical records routinely collected from PLWH receiving care at the DREAM centers. These records include comprehensive demographic, clinical, and treatment information, along with viral load (VL) results and resistance testing data. The study period extended from July 1, 2022, to December 31, 2023, covering all patients who underwent VL testing during this time. Population and Sample The study population included people living with PLWH who attended the selected DREAM centers during the study period. From this group, all the PLWH who met the eligibility criteria were involved. Inclusion and Exclusion Criteria Patients included in this study were those who had been on ART for a minimum of three months and who received a viral load result between July 2022 and December 2023. Only patients with complete clinical records and valid VL results were included in the analysis. Patients who lacked VL data or had incomplete records were excluded from the study. Variables and Outcomes The primary outcome was virological suppression, defined as a viral load of less than 1,000 copies/mL [ 12 ]. Patients with a VL > 1000 were subjected to an enhanced adherence counselling and a second VL was prescribed after three months. Patients who were not resuppressed at this second VL were eligible for resistance testing. Due to logistic constraints and elevated costs, resistance testing was available only for a minority of patients. Key demographic variables included age, categorized into predefined groups, and sex. Clinical variables, such as duration on ART and the months between ART initiation and VL testing, were calculated directly from the data. Geographic variables were based on the patient's treatment center. These variables were analyzed in relation to virological outcomes. Resistance Testing Resistance to DTG was assessed using an in-house genotyping method optimized by Dream molecular laboratories. RNA was extracted from plasma samples using the Qiagen QIAamp Viral RNA kit. Reverse transcription PCR and amplification through nested PCR were performed at the DREAM laboratory in Zimpeto. Amplified products were sent to INQABA Biotechnical Industries, Pretoria, South Africa, where the sequencing process (Sanger method) and the reads of the obtained sequences were conducted. Mutation detection was conducted using DNAStar LASERGENE software in Zimpeto DREAM lab, and the interpretation of resistance patterns was based on the Stanford HIV Drug Resistance Database. The description and evaluation of the in-house genotyping antiretroviral resistance assay was detailed elsewhere [ 13 ]. Statistical Analyses Data were processed and analyzed using R Studio (v 2023.09.1 + 494). Descriptive statistics were computed for all relevant variables. Categorical variables, such as sex and viral suppression status, were reported as frequencies and percentages. Continuous variables, such as age and duration on ART, were reported as median and interquartile range (IQR) or categorized. Chi-square tests were used to examine associations between categorical variables. A multivariate logistic regression model was built to identify independent predictors of viral suppression, including general data such as age, sex, and time on ART. The variables included in the regression model as factors, and results were expressed as odds ratios (OR) with 95% confidence intervals (CI). Ethics The study was conducted in compliance with the ethical standards outlined in the Declaration of Helsinki. Ethical approval was granted by the National Bioethics Committee for Health (CNBS) of Mozambique. The approval, with reference number 430/CNBS/24, was issued on July 19, 2024. Patient anonymity and confidentiality were rigorously maintained throughout the study, and data were handled in a secure and ethical manner in line with established protocols. The study was deemed exempt from the requirement for informed consent, as it involved a retrospective analysis of routine data. This exemption was granted by the CNBS of Mozambique as part of the ethical approval process. RESULTS During the study period, a total of 30,906 PLWH were in care in the selected centers. Among them, 29,601 patients (95.8%) met the inclusion criteria, and were included in the analytic sample; Table 1 reports the general characteristics of the sample. Median age was 41 years (IQR: 33–49) and a median time on ART 98 months (IQR: 60–145). The majority of patients (29,051/29,601 = 98.1%) were on a DTG-based regimen, thus the analysis of viral suppression focuses exclusively on these patients; the overall viral suppression rate among PLWH on DTG-based therapy was 95% (27,622/29,051). Table 1 General characteristics of the entire study population Entire sample DTG-based regimen (n = 29051) Non DTG-based regimen (n = 550) Variable N Percentage N Percentage N Percentage Age Group (0–18) 1,916 6.4 1,885 6.5 31 5.6 Age Group (18–25) 1,847 6.2 1,789 6.2 58 10.5 Age Group (25–50) 18,959 64.0 18,636 64.1 323 58.7 Age Group (> 50) 6,879 23.2 6,741 23.2 138 25.1 Sex (Female) 20,400 68.9 20,018 68.9 382 69.5 Sex (Male) 9,201 31.1 9,033 31.1 168 30.5 Time in therapy (0–1 year) 1,834 6.2 1,797 6.2 37 6.7 Time in therapy (1–5 years) 8,357 28.2 8,211 28.3 146 26.5 Time in therapy (> 5 years) 19,410 65.6 19,043 65.6 367 66.7 Centro (Beira) 4,407 14.9 4,308 14.8 99 18.0 Centro (Machava) 4,301 14.5 4,273 14.7 28 5.1 Centro (Manga Chingussura) 6,911 23.3 6,775 23.3 136 24.7 Centro (Maputo city) 5,448 18.4 5,355 18.4 93 16.9 Centro (Matola 2) 2,650 9.0 2,602 9.0 48 8.7 Centro (Quelimane) 3,271 11.1 3,229 11.1 42 7.6 Centro (Zimpeto) 2,613 8.8 2,509 8.6 104 18.9 DTG containing regimen 29,051 98.1 Non-DTG regimen 550 1.9 Viral suppression 28,180 95.2 27,697 95.3 483 87.8 No Viral suppression 1,421 4.8 1,354 4.7 67 12.2 Prevalence of Viral Suppression by Site, Sex, and Time on ART (DTG patients only) As shown in Fig. 1 , viral suppression rates varied marginally by sex (panel A); female patients on DTG had a slightly higher viral suppression rate (19,017/20,018 = 95.0%) compared to male patients (8,500/9,033 = 94.1%). In terms of age, older patients on DTG showed higher suppression rates. Those aged 50 and above had the highest suppression rate (6,552/6,741 = 97.2%), while the youngest group (0–18 years) showed the lowest rate (1,600/1,885 = 84.9%) (Fig. 1 , panel B). As shown in Fig. 1 panel C, Machava (Maputo Province) showed the highest suppression rate (4,141/4,273 = 96.9%), followed by Maputo City Centre (5,141/5,355 = 96.0%) and Beira City Centre (4,114/4,308 = 95.5%). Quelimane City had the lowest viral suppression rate, at 3,129/3,229 = 91.7%. These rates refer exclusively to patients receiving DTG-based treatment. When stratified by time on ART, patients on DTG for more than five years exhibited the highest suppression rate (18,186/19,043 = 95.5%), while those on DTG for less than one year showed the lowest rate of suppression (1,619/1,797 = 90.1%) (Fig. 1 panel D). Multivariate Analysis (DTG patients only) The multivariate logistic regression analysis was conducted exclusively on the subset of patients receiving DTG-based therapy. The model included age, sex, time on ART, and treatment site to identify independent predictors of viral suppression as shown in Table 2 . Table 2 Multivariate logistic regression analysis of factors associated with viral suppression among patients on Dolutegravir (DTG)-based therapy. Variable Odds Ratio (OR) 95% Confidence Interval (CI) P-value Age (> 50 vs < 50) 2.45 1.85‚ 3.26 5 years vs < 1 year) 1.92 1.44‚ 2.58 < 0.001 Sex (Male vs Female) 0.85 0.75‚ 0.97 0.02 Location (Quelimane vs Machava) 0.67 0.52‚ 0.86 0.01 The analysis demonstrated that older age and longer time on ART were associated with higher odds of viral suppression. Specifically, patients aged 50 and above had significantly higher odds of achieving viral suppression compared to younger patients (OR: 2.45, 95% CI: 1.85–3.26). Similarly, patients on DTG for more than five years had higher odds of suppression (OR: 1.92, 95% CI: 1.44–2.58) compared to those on ART for less than one year. Male patients had slightly lower odds of viral suppression compared to female patients (OR: 0.85, 95% CI: 0.75–0.97). Geographic differences were also observed, with patients in Quelimane City showing lower odds of suppression compared to those in Machava (OR: 0.67, 95% CI: 0.52–0.86). DTG Resistance and Mutations Among patients with virological failure (viral load > 1,000 copies/mL), 74 samples were sent for resistance testing. Resistance testing was successfully performed in 33 cases, of which 17 were tested for DTG resistance. As shown in Table 3 , out of the 17 patients, 8 displayed major mutations conferring resistance to DTG; among them, 5 showed the E138K mutation, and another 5 patients presented the G118R mutation, variably associated with other major mutations. Table 3 Distribution of resistance-associated mutations identified in patients with virological failure receiving Dolutegravir (DTG). Mutation Combination Number of Patients G118R + E138A 1 R263K only 2 E138K + G140A + S147G + Q148R 1 G118R + E138K + R263K 1 G118R + E138K + Q146P 1 G118R + E138K + T66A 1 G118R + E138K + T66I 1 DISCUSSION This study shows high rates of viral suppression (95%) among individuals receiving DTG-based ART at Mozambique’s DREAM centers, with older age, longer duration on ART, and female sex positively associated with better outcomes. However, the detection of DTG resistance in 8 out of 17 patients tested for major mutations underscores the need for ongoing monitoring and surveillance. These findings align with global trends and reinforce the efficacy of DTG in achieving strong viral suppression across various clinical settings [ 14 , 15 ]. Nevertheless, the emergence of resistance in Mozambique, as also noted by WHO, calls for comprehensive resistance surveillance, particularly in populations with prior ART exposure or inconsistent adherence [ 5 ]. Despite the strengths of this study, several limitations should be acknowledged. The retrospective design limits the ability to establish causality, and the focus on DREAM centers may reduce the generalizability of the findings. Additionally, the small sample size for resistance testing represents a significant limitation. The 18-month observation period may not capture long-term trends in DTG efficacy or resistance, underscoring the need for extended follow-up studies. Another limitation is the inclusion of only a limited number of variables in the multivariate analysis, which may not fully capture the clinical complexity of patients. However, this approach adds value to the analysis by providing useful data for profiling the risk of viral suppression failure based on baseline variables available even in lower-resource settings. Future research should address these limitations through prospective cohort studies that assess the long-term efficacy of DTG and the factors influencing resistance development in resource-limited settings. Expanding resistance testing and incorporating adherence data would provide a more comprehensive understanding of treatment outcomes. Our results emphasize the importance of sustained viral load monitoring and resistance testing across Sub-Saharan Africa to optimize treatment outcomes. Surveillance systems, as many authors suggest, are critical for early detection of resistance and timely adaptation of treatment strategies [ 16 ]. Investments in reinforcing these networks are urgently needed in regions with growing ART programs. Innovative service models, such as Differentiated Service Delivery (DSD), are essential to address the unique needs of patient subgroups. These models should not only offer multi-month drug delivery but also incorporate personalized care pathways, tailored laboratory monitoring, and counseling sessions [ 17 ]. Pilot projects in Sub-Saharan Africa have successfully targeted populations with prior ART exposure, adolescents, men, sex workers, and children, showing improved adherence and reduced resistance risks [ 18 – 22 ]. While several practices currently being implemented across African countries—such as HIV self-testing, pharmacy-based ART dispensing, and six-month drug dispensing—are supported by international guidelines and offer clear advantages, there are concerns about their cumulative impact when applied simultaneously without adequate support [ 23 , 24 ]. Each practice, on its own, has been shown to improve access and convenience for patients, with evidence often supporting their effectiveness. However, there is a risk that the combination of these service simplifications might unintentionally reduce the quality of care. Although these concerns may affect only a small percentage of patients, given the large number of people receiving ART in Africa, even small deviations could have significant public health implications, potentially contributing to the spread of DTG resistance. These service-level risks are compounded by structural challenges, such as limited resources and the complexity of managing co-infections and comorbidities. If these challenges are not adequately addressed, we risk a significant resurgence of drug resistance, undermining years of progress. Moreover, it is crucial not to overlook the lessons learned from the history of HIV care. In earlier phases of the HIV response, services that initially appeared to be less resource-intensive did not always lead to better health outcomes. There are numerous examples where more comprehensive, though initially more expensive, interventions proved to be more effective in the long term (as seen with the shift from single-dose nevirapine to triple therapy for the prevention of mother-to-child transmission) [ 25 – 27 ]. This highlights the importance of thoroughly evaluating models that seem simpler or cheaper on the surface. As we explore new models of care, it is essential to conduct cost-effectiveness studies that consider the potential long-term risks, such as the development of resistance. The scientific community and policymakers should critically assess these models and avoid rushing into cost-saving solutions without fully understanding their broader implications on patient outcomes and public health [ 28 ]. The rapid emergence of DTG resistance calls for more cautious public health strategies. Policymakers must avoid oversimplification and instead focus on differentiated services that account for the complexity of HIV [ 29 ]. Expanding resistance surveillance systems is particularly critical in regions with growing ART programs, enabling early detection and timely modification of treatment protocols. Furthermore, viral load testing and resistance monitoring must be fully integrated into national HIV programs to adapt treatment strategies based on emerging resistance patterns. In conclusion, while this study demonstrates the effectiveness of Dolutegravir-based ART in Mozambique, with high rates of viral suppression across diverse patient groups, the increasing emergence of DTG resistance serves as a stark warning. With millions of people in Africa relying on DTG, the spread of resistance mutations poses a serious public health threat, also considering that new drugs and new drug classes are not at the horizon in Africa, therefore Dolutegravir efficacy needs to be preserved at best, since it represents the pillar of the current and perhaps future therapies. Urgent action is needed to rethink HIV care strategies in the region, focusing on differentiated service delivery, enhanced surveillance and resistance testing, digitalization, and effective patient tracking systems. Without prompt intervention, the significant progress in HIV management could be at risk. CONCLUSION In conclusion, this study provides compelling evidence for the effectiveness of DTG-based antiretroviral therapy in Mozambique, demonstrating high rates of viral suppression across diverse patient populations. Our findings of 95% viral suppression among patients on DTG-based regimens underscore its potential as a cornerstone of HIV treatment in resource-limited settings. The identification of factors associated with better outcomes, such as older age and longer duration on ART, offers valuable insights for tailoring treatment approaches. However, the emergence of DTG resistance in a subset of patients serves as a critical reminder of the need for continued vigilance and robust monitoring systems. These results not only validate the current treatment guidelines but also highlight the importance of personalized care and ongoing surveillance in HIV management. As we move forward, the integration of these findings into clinical practice and policy-making will be crucial in optimizing HIV treatment outcomes, reducing transmission rates, and ultimately contributing to the global goal of ending the HIV epidemic. Declarations AKNOLEDGEMNTS We would like to express our sincere gratitude to Professor Federico Perno and Professor Maria Cristina Marazzi for their continuous support and inspiration for this work. Their guidance has been invaluable throughout this research. We also extend our heartfelt thanks to the African patients involved in this study. It is our hope that this research will contribute to improving their health and quality of life, and benefit many others in similar circumstances in the future. CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest related to this study. FUNDING DECLARATION This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. AUTHORS’ CONTRIBUTION AMD conducted the analysis and drafted the manuscript.NM supervised data collection. SO reviewed the manuscript and provided insights into data interpretation. EU and MR managed the clinical data collection from patients. ZS supervised the laboratory data management. GG supervised data collection and reviewed the manuscript. FC conceptualized the study, supervised the analysis, and guided the interpretation of results. References UNAIDS, Global HIV. & AIDS statistics — Fact sheet. Global HIV & AIDS statistics — Fact sheet , https://www.unaids.org/en/resources/fact-sheet (2024). UNAIDS. The urgency of now: AIDS at a crossroads., https://crossroads.unaids.org (2024). Zhao AV, Crutchley RD, Guduru RC, et al. A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection. Retrovirology. 2022;19:22. World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection., https://iris.who.int/bitstream/handle/10665/277395/WHO-CDS-HIV-18.51-eng.pdf?sequence=1 (2018). World Health Organization. HIV drug resistance: brief report 2024. https://www.who.int/publications/i/item/9789240086319 (2024). UNAIDS, Country factsheets - MOZAMBIQUE. 2023, https://www.unaids.org/en/regionscountries/countries/mozambique (2024, accessed 26 September 2024). Ministério da Saúde. Direcção Nacional de Saúde Pública, PNC ITS-HIV/SIDA. Normas Clínicas Actualizadas para o seguimento do paciente HIV positivo. https://comitetarvmisau.co.mz/docs/orientacoes_nacionais/Circular_Normas_Clínicas_Actualizadas_29_11_19.pdf (2019). Kamori D, Barabona G. Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment? Front Virol. 2023;3:1253661. Loosli T, Hossmann S, Ingle SM, et al. HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis. Lancet HIV. 2023;10:e733–41. Ngoufack Jagni Semengue E, Santoro MM, Ndze VN, et al. HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis. PLOS global public health. 2022;2:e0000826. Community of Sant’Egidio. DREAM Program in Mozambique. https://www.dream-health.org/where-we-are/mozambique/?lang=en (2020). World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. World Health Organization; 2021. Peduzzi C, Pierotti P, Venturi G, et al. Performance of an in-house genotypic antiretroviral resistance assay in patients pretreated with multiple human immunodeficiency virus type 1 protease and reverse transcriptase inhibitors. J Clin Virol. 2002;25:57–62. Kanters S, Vitoria M, Zoratti M et al. Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: a systematic literature review and network meta-analysis. EClinicalMedicine ; 28. Punekar Y, Parks D, Joshi M, et al. Effectiveness and safety of dolutegravir two-drug regimens in virologically suppressed people living with HIV: a systematic literature review and meta‐analysis of real‐world evidence. HIV Med. 2021;22:423–33. Fokam J, Inzaule S, Colizzi V, et al. HIV drug resistance to integrase inhibitors in low-and middle-income countries. Nat Med. 2024;30:618–9. The International AIDS Society. Differentiated Service Delivery, https://www.differentiatedservicedelivery.org (2024). Ciccacci F, Ismael F, Chume V et al. Enhancing retention in care in HIV-infected adolescents during COVID-19 in Mozambique: results from the DREAM program. Int J Adolesc Med Health. Epub ahead of print 2023. 10.1515/ijamh-2022-0107 Fox MP, Pascoe S, Huber AN, et al. Adherence clubs and decentralized medication delivery to support patient retention and sustained viral suppression in care: Results from a cluster-randomized evaluation of differentiated ART delivery models in South Africa. PLoS Med. 2019;16:e1002874. Kouamou V, Manasa J, Katzenstein D, et al. Drug resistance and optimizing dolutegravir regimens for adolescents and young adults failing antiretroviral therapy. Aids. 2019;33:1729–37. Long L, Kuchukhidze S, Pascoe S, et al. Retention in care and viral suppression in differentiated service delivery models for HIV treatment delivery in sub-Saharan Africa: a rapid systematic review. J Int AIDS Soc. 2020;23:e25640. Triulzi I, Ciccacci F, Palla I et al. Improving Male Partner Involvement in HIV-Positive Women’s Care Through Behavioral Change Interventions in Malawi (WeMen Study): A Prospective, Controlled Before-and-After Study. Frontiers in Public Health ; 10. Hlongwa M, Moyo E, Dzinamarira T. Approaches for improving linkage to HIV care among HIV self-testing individuals in sub-Saharan Africa. BMJ Global Health. 2023;8:e012664. Terefe B, Jembere MM, Reda GB, et al. Knowledge, and utilization of HIV self-testing, and its associated factors among women in sub–Saharan Africa: evidence from 21 countries demographic and health survey. BMC Public Health. 2024;24:1960. Orlando S, Marazzi MC, Mancinelli S, et al. Cost-effectiveness of using HAART in prevention of mother-to-child transmission in the DREAM-Project Malawi. JAIDS J Acquir Immune Defic Syndr. 2010;55:631–4. Orlando S, Triulzi I, Ciccacci F, et al. Delayed diagnosis and treatment of tuberculosis in HIV + patients in Mozambique: A cost-effectiveness analysis of screening protocols based on four symptom screening, smear microscopy, urine LAM test and Xpert MTB/RIF. PLoS ONE. 2018;13:e0200523. Siapka M, Remme M, Obure CD, et al. Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low-and middle-income countries. Bull World Health Organ. 2014;92:499–AD511. Sarkar S, Corso P, Ebrahim-Zadeh S, et al. Cost-effectiveness of HIV prevention interventions in sub-Saharan Africa: a systematic review. EClinicalMedicine. 2019;10:10–31. Mody A, Sohn AH, Iwuji C, et al. HIV epidemiology, prevention, treatment, and implementation strategies for public health. Lancet. 2024;403:471–92. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2025 Read the published version in AIDS Research and Therapy → Version 1 posted Editorial decision: Revision requested 20 Dec, 2024 Editor assigned by journal 19 Dec, 2024 Submission checks completed at journal 19 Dec, 2024 First submitted to journal 19 Dec, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5676736","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":392654155,"identity":"6eaf96de-4bd4-41ca-bc2b-874a0636cef2","order_by":0,"name":"Anna Maria Doro Altan","email":"","orcid":"","institution":"Link Campus University","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"Maria Doro","lastName":"Altan","suffix":""},{"id":392654156,"identity":"11bee9aa-8814-4d65-b0e3-531f31aa758f","order_by":1,"name":"Noorjehan Majid","email":"","orcid":"","institution":"Community of Sant’Egidio","correspondingAuthor":false,"prefix":"","firstName":"Noorjehan","middleName":"","lastName":"Majid","suffix":""},{"id":392654157,"identity":"ca41f2aa-e88d-41b3-a57c-aa842b5f9305","order_by":2,"name":"Stefano Orlando","email":"","orcid":"","institution":"University of Rome Tor Vergata","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Orlando","suffix":""},{"id":392654158,"identity":"1323d3ee-cbd3-4170-8990-0726f303028b","order_by":3,"name":"Elton Uamusse","email":"","orcid":"","institution":"Community of Sant’Egidio","correspondingAuthor":false,"prefix":"","firstName":"Elton","middleName":"","lastName":"Uamusse","suffix":""},{"id":392654159,"identity":"16830223-b0a4-4fd0-b961-3d603e321369","order_by":4,"name":"Marcia Rafael","email":"","orcid":"","institution":"Community of Sant’Egidio","correspondingAuthor":false,"prefix":"","firstName":"Marcia","middleName":"","lastName":"Rafael","suffix":""},{"id":392654160,"identity":"a0cae617-b348-47ae-8bda-8facd9a8f660","order_by":5,"name":"Zita Sidumo","email":"","orcid":"","institution":"Community of Sant’Egidio","correspondingAuthor":false,"prefix":"","firstName":"Zita","middleName":"","lastName":"Sidumo","suffix":""},{"id":392654161,"identity":"474eb407-b1da-43a5-a2c8-bf88522afe49","order_by":6,"name":"Giovanni Guidotti","email":"","orcid":"","institution":"ASL Roma 1","correspondingAuthor":false,"prefix":"","firstName":"Giovanni","middleName":"","lastName":"Guidotti","suffix":""},{"id":392654162,"identity":"fd4a3f73-b42d-4fc0-ba9c-cd98f840276b","order_by":7,"name":"Fausto Ciccacci","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYBAC9gYogw1CSciByAMP8GjhOQBSgaTFGKwlgRgtMJAIthavFvYzxp8/VDDI87EffvjhR41F+vywww+BttjJ6Tbg0MKTYyZx4AyDYRtPmrFkzzGJ3I230wyAWpKNzQ5g12LPkGPGcLCNIYFNgodBmrEBqGV2AkjLgcRtOLTw8L8x/gDVwvwbqCXdcHb6B/xaJHIMJKBa2EC2JMhL5xCwReJZmcSZMxIgv5hZAv1iuEE6p+BAggFuv/DwJ2/+UFFhIy/ffvjxjR81dfLys9M3f/hQYSeHSwsUSCCYBmCVBniVowH5BlJUj4JRMApGwUgAAKVbWC0BomqPAAAAAElFTkSuQmCC","orcid":"","institution":"University of Rome Tor Vergata","correspondingAuthor":true,"prefix":"","firstName":"Fausto","middleName":"","lastName":"Ciccacci","suffix":""}],"badges":[],"createdAt":"2024-12-19 12:23:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5676736/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5676736/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12981-025-00708-w","type":"published","date":"2025-01-30T15:57:29+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72337371,"identity":"cd3d5a3d-7ff1-44e6-8580-65b422bcd162","added_by":"auto","created_at":"2024-12-25 16:02:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":208502,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of viral suppression rates among patients on Dolutegravir (DTG)-based therapy by sex (Panel A), by age group (Panel B), by treatment sites (Panel C), and by the duration of therapy (Panel D).\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5676736/v1/fd2615766a634f90bb43356d.png"},{"id":75351825,"identity":"3c3a220e-f601-488a-a348-5b7dcd0e3511","added_by":"auto","created_at":"2025-02-03 16:12:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":972008,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5676736/v1/3c129cdd-e6f0-4c2c-9ac7-f896d2dcf0b4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Virological Outcomes and Dolutegravir Resistance Mutations in HIV-infected Patients: A Multicenter Retrospective Cohort Study in Mozambique","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe global HIV epidemic remains one of the most significant public health challenges, with an estimated 39.9\u0026nbsp;million people living with HIV worldwide as of 2023 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The introduction of antiretroviral therapy (ART) has been crucial in reducing morbidity and mortality associated with HIV [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Among the various classes of ART drugs, integrase strand transfer inhibitors (INSTIs) have become a cornerstone in HIV treatment due to their high efficacy, good tolerability, and limited drug interactions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Dolutegravir (DTG), a second-generation INSTI, has emerged as a preferred option in first-line ART regimens for its ability to achieve rapid and sustained viral suppression; in 2018, the World Health Organization (WHO) endorsed DTG as part of the preferred ART regimens, particularly in low- and middle-income countries, where the burden of HIV is disproportionately high [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. WHO reports that up to now 91% of 127 reporting countries have adopted Dolutegravir (DTG)-based ART as the preferred first-line treatment for adults and adolescents; additionally, 77% of 116 countries have incorporated DTG into second-line therapy, and 69% of 114 countries prioritize DTG-based regimens for infants and children​ [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMozambique is one of the countries most affected by the HIV epidemic, with approximately 2.4\u0026nbsp;million people living with the virus, according to the most recent UNAIDS estimates ​ [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. According to UNAIDS, in 2023 Mozambique had achieved ART coverage for about 87.5% of people living with HIV (PLWH)​ [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. DTG has been a key part of Mozambique\u0026rsquo;s national HIV treatment strategy since its introduction into first-line ART regimens in 2019 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough DTG has proven highly effective in managing HIV, the emergence of resistance remains a growing concern, especially in resource-limited settings​ [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Recent studies from the field have reported higher-than-expected rates of DTG resistance, particularly in populations with previous exposure to antiretroviral therapy, highlighting challenges in real-world implementation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The most commonly identified mutations associated with DTG resistance in Sub-Saharan Africa, include G118R, E138K, all of which compromise at different levels the drug\u0026rsquo;s efficacy, posing a significant threat to the effectiveness of DTG-based regimens in the continent, where the HIV burden is highest [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn Mozambique, where access to advanced diagnostic tools is often limited, data on drug resistance are sparse.\u003c/p\u003e \u003cp\u003eThe primary objective of this study is to evaluate the prevalence of viral suppression among patients on DTG and to assess the emergence of drug resistance. In doing so, it aims to identify key factors that may contribute to treatment failure, such as prior ART exposure, and time on treatment. A secondary objective is to report data on mutations detected in the small number of patients who were able to access resistance testing.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eWe conducted a multicenter retrospective cohort study to evaluate virological outcomes in patients on DTG-based regimens. By reviewing historical data, we assessed the prevalence of virological suppression, and the emergence of DTG resistance during the study period. We also compared virologically suppressed patients with those who were not suppressed, allowing for a more comprehensive evaluation of the real-world effectiveness of DTG in Mozambique.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSetting\u003c/h3\u003e\n\u003cp\u003eThe study was conducted across seven DREAM program centers located in different regions of Mozambique. These include three centers in Maputo City (Maputo City, Machava, and Zimpeto), which provide services to the southern region of the country. Additionally, Matola 2, situated in Maputo Province, serves the peri-urban area surrounding the capital. In the central region, two centers in Beira (Mangachingussura and Beira City) offer comprehensive healthcare services, particularly for urban and semi-urban populations. Finally, Quelimane City, located in the Zambezia Province, extends coverage to the northern part of Mozambique, ensuring a diverse and geographically representative patient population.\u003c/p\u003e \u003cp\u003eThese centers provide community-based healthcare with a focus on HIV treatment and ART [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The selection of these centers ensured a diverse and representative sample of PLWH receiving DTG treatment, encompassing a range of geographic and demographic profiles.\u003c/p\u003e\n\u003ch3\u003eData Sources\u003c/h3\u003e\n\u003cp\u003eData for this study were derived from electronic medical records routinely collected from PLWH receiving care at the DREAM centers. These records include comprehensive demographic, clinical, and treatment information, along with viral load (VL) results and resistance testing data. The study period extended from July 1, 2022, to December 31, 2023, covering all patients who underwent VL testing during this time.\u003c/p\u003e\n\u003ch3\u003ePopulation and Sample\u003c/h3\u003e\n\u003cp\u003eThe study population included people living with PLWH who attended the selected DREAM centers during the study period. From this group, all the PLWH who met the eligibility criteria were involved.\u003c/p\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003ePatients included in this study were those who had been on ART for a minimum of three months and who received a viral load result between July 2022 and December 2023. Only patients with complete clinical records and valid VL results were included in the analysis. Patients who lacked VL data or had incomplete records were excluded from the study.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eVariables and Outcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was virological suppression, defined as a viral load of less than 1,000 copies/mL [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Patients with a VL\u0026thinsp;\u0026gt;\u0026thinsp;1000 were subjected to an enhanced adherence counselling and a second VL was prescribed after three months. Patients who were not resuppressed at this second VL were eligible for resistance testing. Due to logistic constraints and elevated costs, resistance testing was available only for a minority of patients. Key demographic variables included age, categorized into predefined groups, and sex. Clinical variables, such as duration on ART and the months between ART initiation and VL testing, were calculated directly from the data. Geographic variables were based on the patient's treatment center. These variables were analyzed in relation to virological outcomes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eResistance Testing\u003c/h3\u003e\n\u003cp\u003eResistance to DTG was assessed using an in-house genotyping method optimized by Dream molecular laboratories. RNA was extracted from plasma samples using the Qiagen QIAamp Viral RNA kit. Reverse transcription PCR and amplification through nested PCR were performed at the DREAM laboratory in Zimpeto. Amplified products were sent to INQABA Biotechnical Industries, Pretoria, South Africa, where the sequencing process (Sanger method) and the reads of the obtained sequences were conducted. Mutation detection was conducted using DNAStar LASERGENE software in Zimpeto DREAM lab, and the interpretation of resistance patterns was based on the Stanford HIV Drug Resistance Database. The description and evaluation of the in-house genotyping antiretroviral resistance assay was detailed elsewhere [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eStatistical Analyses\u003c/h3\u003e\n\u003cp\u003eData were processed and analyzed using R Studio (v 2023.09.1\u0026thinsp;+\u0026thinsp;494). Descriptive statistics were computed for all relevant variables. Categorical variables, such as sex and viral suppression status, were reported as frequencies and percentages. Continuous variables, such as age and duration on ART, were reported as median and interquartile range (IQR) or categorized. Chi-square tests were used to examine associations between categorical variables. A multivariate logistic regression model was built to identify independent predictors of viral suppression, including general data such as age, sex, and time on ART. The variables included in the regression model as factors, and results were expressed as odds ratios (OR) with 95% confidence intervals (CI).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003e The study was conducted in compliance with the ethical standards outlined in the Declaration of Helsinki. Ethical approval was granted by the National Bioethics Committee for Health (CNBS) of Mozambique. The approval, with reference number 430/CNBS/24, was issued on July 19, 2024. Patient anonymity and confidentiality were rigorously maintained throughout the study, and data were handled in a secure and ethical manner in line with established protocols. The study was deemed exempt from the requirement for informed consent, as it involved a retrospective analysis of routine data. This exemption was granted by the CNBS of Mozambique as part of the ethical approval process.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eDuring the study period, a total of 30,906 PLWH were in care in the selected centers. Among them, 29,601 patients (95.8%) met the inclusion criteria, and were included in the analytic sample; Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e reports the general characteristics of the sample. Median age was 41 years (IQR: 33\u0026ndash;49) and a median time on ART 98 months (IQR: 60\u0026ndash;145). The majority of patients (29,051/29,601\u0026thinsp;=\u0026thinsp;98.1%) were on a DTG-based regimen, thus the analysis of viral suppression focuses exclusively on these patients; the overall viral suppression rate among PLWH on DTG-based therapy was 95% (27,622/29,051).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral characteristics of the entire study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eEntire sample\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eDTG-based regimen (n\u0026thinsp;=\u0026thinsp;29051)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNon DTG-based regimen (n\u0026thinsp;=\u0026thinsp;550)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVariable\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ePercentage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003ePercentage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003ePercentage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge Group (0\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,916\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,885\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge Group (18\u0026ndash;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,847\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge Group (25\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18,959\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18,636\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e58.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge Group (\u0026gt;\u0026thinsp;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,741\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20,400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20,018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e382\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e69.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9,201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9,033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime in therapy (0\u0026ndash;1 year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,834\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,797\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime in therapy (1\u0026ndash;5 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8,357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime in therapy (\u0026gt;\u0026thinsp;5 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19,410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19,043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e66.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Beira)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Machava)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4,273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Manga Chingussura)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,911\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6,775\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Maputo city)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,448\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Matola 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,650\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Quelimane)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,229\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentro (Zimpeto)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,509\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDTG containing regimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29,051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-DTG regimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e550\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eViral suppression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28,180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27,697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e87.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo Viral suppression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,421\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePrevalence of Viral Suppression by Site, Sex, and Time on ART (DTG patients only)\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, viral suppression rates varied marginally by sex (panel A); female patients on DTG had a slightly higher viral suppression rate (19,017/20,018\u0026thinsp;=\u0026thinsp;95.0%) compared to male patients (8,500/9,033\u0026thinsp;=\u0026thinsp;94.1%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn terms of age, older patients on DTG showed higher suppression rates. Those aged 50 and above had the highest suppression rate (6,552/6,741\u0026thinsp;=\u0026thinsp;97.2%), while the youngest group (0\u0026ndash;18 years) showed the lowest rate (1,600/1,885\u0026thinsp;=\u0026thinsp;84.9%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, panel B).\u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e panel C, Machava (Maputo Province) showed the highest suppression rate (4,141/4,273\u0026thinsp;=\u0026thinsp;96.9%), followed by Maputo City Centre (5,141/5,355\u0026thinsp;=\u0026thinsp;96.0%) and Beira City Centre (4,114/4,308\u0026thinsp;=\u0026thinsp;95.5%). Quelimane City had the lowest viral suppression rate, at 3,129/3,229\u0026thinsp;=\u0026thinsp;91.7%. These rates refer exclusively to patients receiving DTG-based treatment.\u003c/p\u003e \u003cp\u003eWhen stratified by time on ART, patients on DTG for more than five years exhibited the highest suppression rate (18,186/19,043\u0026thinsp;=\u0026thinsp;95.5%), while those on DTG for less than one year showed the lowest rate of suppression (1,619/1,797\u0026thinsp;=\u0026thinsp;90.1%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e panel D).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMultivariate Analysis (DTG patients only)\u003c/h2\u003e \u003cp\u003eThe multivariate logistic regression analysis was conducted exclusively on the subset of patients receiving DTG-based therapy. The model included age, sex, time on ART, and treatment site to identify independent predictors of viral suppression as shown in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate logistic regression analysis of factors associated with viral suppression among patients on Dolutegravir (DTG)-based therapy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio (OR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence Interval (CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (\u0026gt;\u0026thinsp;50 vs\u0026thinsp;\u0026lt;\u0026thinsp;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.85\u0026sbquo; 3.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime on ART (\u0026gt;\u0026thinsp;5 years vs\u0026thinsp;\u0026lt;\u0026thinsp;1 year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.44\u0026sbquo; 2.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Male vs Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.75\u0026sbquo; 0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation (Quelimane vs Machava)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52\u0026sbquo; 0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe analysis demonstrated that older age and longer time on ART were associated with higher odds of viral suppression. Specifically, patients aged 50 and above had significantly higher odds of achieving viral suppression compared to younger patients (OR: 2.45, 95% CI: 1.85\u0026ndash;3.26). Similarly, patients on DTG for more than five years had higher odds of suppression (OR: 1.92, 95% CI: 1.44\u0026ndash;2.58) compared to those on ART for less than one year.\u003c/p\u003e \u003cp\u003eMale patients had slightly lower odds of viral suppression compared to female patients (OR: 0.85, 95% CI: 0.75\u0026ndash;0.97). Geographic differences were also observed, with patients in Quelimane City showing lower odds of suppression compared to those in Machava (OR: 0.67, 95% CI: 0.52\u0026ndash;0.86).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eDTG Resistance and Mutations\u003c/h2\u003e \u003cp\u003eAmong patients with virological failure (viral load\u0026thinsp;\u0026gt;\u0026thinsp;1,000 copies/mL), 74 samples were sent for resistance testing. Resistance testing was successfully performed in 33 cases, of which 17 were tested for DTG resistance. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, out of the 17 patients, 8 displayed major mutations conferring resistance to DTG; among them, 5 showed the E138K mutation, and another 5 patients presented the G118R mutation, variably associated with other major mutations.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of resistance-associated mutations identified in patients with virological failure receiving Dolutegravir (DTG).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMutation Combination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of Patients\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG118R\u0026thinsp;+\u0026thinsp;E138A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR263K only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE138K\u0026thinsp;+\u0026thinsp;G140A\u0026thinsp;+\u0026thinsp;S147G\u0026thinsp;+\u0026thinsp;Q148R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG118R\u0026thinsp;+\u0026thinsp;E138K\u0026thinsp;+\u0026thinsp;R263K\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG118R\u0026thinsp;+\u0026thinsp;E138K\u0026thinsp;+\u0026thinsp;Q146P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG118R\u0026thinsp;+\u0026thinsp;E138K\u0026thinsp;+\u0026thinsp;T66A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG118R\u0026thinsp;+\u0026thinsp;E138K\u0026thinsp;+\u0026thinsp;T66I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study shows high rates of viral suppression (95%) among individuals receiving DTG-based ART at Mozambique\u0026rsquo;s DREAM centers, with older age, longer duration on ART, and female sex positively associated with better outcomes. However, the detection of DTG resistance in 8 out of 17 patients tested for major mutations underscores the need for ongoing monitoring and surveillance. These findings align with global trends and reinforce the efficacy of DTG in achieving strong viral suppression across various clinical settings [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Nevertheless, the emergence of resistance in Mozambique, as also noted by WHO, calls for comprehensive resistance surveillance, particularly in populations with prior ART exposure or inconsistent adherence [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the strengths of this study, several limitations should be acknowledged. The retrospective design limits the ability to establish causality, and the focus on DREAM centers may reduce the generalizability of the findings. Additionally, the small sample size for resistance testing represents a significant limitation. The 18-month observation period may not capture long-term trends in DTG efficacy or resistance, underscoring the need for extended follow-up studies. Another limitation is the inclusion of only a limited number of variables in the multivariate analysis, which may not fully capture the clinical complexity of patients. However, this approach adds value to the analysis by providing useful data for profiling the risk of viral suppression failure based on baseline variables available even in lower-resource settings.\u003c/p\u003e \u003cp\u003eFuture research should address these limitations through prospective cohort studies that assess the long-term efficacy of DTG and the factors influencing resistance development in resource-limited settings. Expanding resistance testing and incorporating adherence data would provide a more comprehensive understanding of treatment outcomes.\u003c/p\u003e \u003cp\u003eOur results emphasize the importance of sustained viral load monitoring and resistance testing across Sub-Saharan Africa to optimize treatment outcomes. Surveillance systems, as many authors suggest, are critical for early detection of resistance and timely adaptation of treatment strategies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Investments in reinforcing these networks are urgently needed in regions with growing ART programs.\u003c/p\u003e \u003cp\u003eInnovative service models, such as Differentiated Service Delivery (DSD), are essential to address the unique needs of patient subgroups. These models should not only offer multi-month drug delivery but also incorporate personalized care pathways, tailored laboratory monitoring, and counseling sessions [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Pilot projects in Sub-Saharan Africa have successfully targeted populations with prior ART exposure, adolescents, men, sex workers, and children, showing improved adherence and reduced resistance risks [\u003cspan additionalcitationids=\"CR19 CR20 CR21\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile several practices currently being implemented across African countries\u0026mdash;such as HIV self-testing, pharmacy-based ART dispensing, and six-month drug dispensing\u0026mdash;are supported by international guidelines and offer clear advantages, there are concerns about their cumulative impact when applied simultaneously without adequate support [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Each practice, on its own, has been shown to improve access and convenience for patients, with evidence often supporting their effectiveness. However, there is a risk that the combination of these service simplifications might unintentionally reduce the quality of care. Although these concerns may affect only a small percentage of patients, given the large number of people receiving ART in Africa, even small deviations could have significant public health implications, potentially contributing to the spread of DTG resistance. These service-level risks are compounded by structural challenges, such as limited resources and the complexity of managing co-infections and comorbidities. If these challenges are not adequately addressed, we risk a significant resurgence of drug resistance, undermining years of progress.\u003c/p\u003e \u003cp\u003eMoreover, it is crucial not to overlook the lessons learned from the history of HIV care. In earlier phases of the HIV response, services that initially appeared to be less resource-intensive did not always lead to better health outcomes. There are numerous examples where more comprehensive, though initially more expensive, interventions proved to be more effective in the long term (as seen with the shift from single-dose nevirapine to triple therapy for the prevention of mother-to-child transmission) [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This highlights the importance of thoroughly evaluating models that seem simpler or cheaper on the surface. As we explore new models of care, it is essential to conduct cost-effectiveness studies that consider the potential long-term risks, such as the development of resistance. The scientific community and policymakers should critically assess these models and avoid rushing into cost-saving solutions without fully understanding their broader implications on patient outcomes and public health [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe rapid emergence of DTG resistance calls for more cautious public health strategies. Policymakers must avoid oversimplification and instead focus on differentiated services that account for the complexity of HIV [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Expanding resistance surveillance systems is particularly critical in regions with growing ART programs, enabling early detection and timely modification of treatment protocols. Furthermore, viral load testing and resistance monitoring must be fully integrated into national HIV programs to adapt treatment strategies based on emerging resistance patterns.\u003c/p\u003e \u003cp\u003eIn conclusion, while this study demonstrates the effectiveness of Dolutegravir-based ART in Mozambique, with high rates of viral suppression across diverse patient groups, the increasing emergence of DTG resistance serves as a stark warning. With millions of people in Africa relying on DTG, the spread of resistance mutations poses a serious public health threat, also considering that new drugs and new drug classes are not at the horizon in Africa, therefore Dolutegravir efficacy needs to be preserved at best, since it represents the pillar of the current and perhaps future therapies. Urgent action is needed to rethink HIV care strategies in the region, focusing on differentiated service delivery, enhanced surveillance and resistance testing, digitalization, and effective patient tracking systems. Without prompt intervention, the significant progress in HIV management could be at risk.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn conclusion, this study provides compelling evidence for the effectiveness of DTG-based antiretroviral therapy in Mozambique, demonstrating high rates of viral suppression across diverse patient populations. Our findings of 95% viral suppression among patients on DTG-based regimens underscore its potential as a cornerstone of HIV treatment in resource-limited settings. The identification of factors associated with better outcomes, such as older age and longer duration on ART, offers valuable insights for tailoring treatment approaches. However, the emergence of DTG resistance in a subset of patients serves as a critical reminder of the need for continued vigilance and robust monitoring systems. These results not only validate the current treatment guidelines but also highlight the importance of personalized care and ongoing surveillance in HIV management. As we move forward, the integration of these findings into clinical practice and policy-making will be crucial in optimizing HIV treatment outcomes, reducing transmission rates, and ultimately contributing to the global goal of ending the HIV epidemic.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAKNOLEDGEMNTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our sincere gratitude to Professor Federico Perno and Professor Maria Cristina Marazzi for their continuous support and inspiration for this work. Their guidance has been invaluable throughout this research.\u003c/p\u003e\n\u003cp\u003eWe also extend our heartfelt thanks to the African patients involved in this study. It is our hope that this research will contribute to improving their health and quality of life, and benefit many others in similar circumstances in the future.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICTS OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest related to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING DECLARATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS’ CONTRIBUTION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAMD conducted the analysis and drafted the manuscript.NM supervised data collection. SO reviewed the manuscript and provided insights into data interpretation. EU and MR managed the clinical data collection from patients. ZS supervised the laboratory data management. GG supervised data collection and reviewed the manuscript. FC conceptualized the study, supervised the analysis, and guided the interpretation of results.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eUNAIDS, Global HIV. \u0026amp; AIDS statistics \u0026mdash; Fact sheet. \u003cem\u003eGlobal HIV \u0026amp; AIDS statistics \u0026mdash; Fact sheet\u003c/em\u003e, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.unaids.org/en/resources/fact-sheet\u003c/span\u003e\u003cspan address=\"https://www.unaids.org/en/resources/fact-sheet\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUNAIDS. The urgency of now: AIDS at a crossroads., \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://crossroads.unaids.org\u003c/span\u003e\u003cspan address=\"https://crossroads.unaids.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao AV, Crutchley RD, Guduru RC, et al. A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection. Retrovirology. 2022;19:22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines. Supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection., \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://iris.who.int/bitstream/handle/10665/277395/WHO-CDS-HIV-18.51-eng.pdf?sequence=1\u003c/span\u003e\u003cspan address=\"https://iris.who.int/bitstream/handle/10665/277395/WHO-CDS-HIV-18.51-eng.pdf?sequence=1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. HIV drug resistance: brief report 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/publications/i/item/9789240086319\u003c/span\u003e\u003cspan address=\"https://www.who.int/publications/i/item/9789240086319\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUNAIDS, Country factsheets - MOZAMBIQUE. 2023, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.unaids.org/en/regionscountries/countries/mozambique\u003c/span\u003e\u003cspan address=\"https://www.unaids.org/en/regionscountries/countries/mozambique\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024, accessed 26 September 2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinist\u0026eacute;rio da Sa\u0026uacute;de. Direc\u0026ccedil;\u0026atilde;o Nacional de Sa\u0026uacute;de P\u0026uacute;blica, PNC ITS-HIV/SIDA. Normas Cl\u0026iacute;nicas Actualizadas para o seguimento do paciente HIV positivo. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://comitetarvmisau.co.mz/docs/orientacoes_nacionais/Circular_Normas_Cl\u0026iacute;nicas_Actualizadas_29_11_19.pdf\u003c/span\u003e\u003cspan address=\"https://comitetarvmisau.co.mz/docs/orientacoes_nacionais/Circular_Normas_Cl\u0026iacute;nicas_Actualizadas_29_11_19.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamori D, Barabona G. Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment? Front Virol. 2023;3:1253661.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoosli T, Hossmann S, Ingle SM, et al. HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy: a collaborative cohort analysis. Lancet HIV. 2023;10:e733\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNgoufack Jagni Semengue E, Santoro MM, Ndze VN, et al. HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: A systematic review and meta-analysis. PLOS global public health. 2022;2:e0000826.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCommunity of Sant\u0026rsquo;Egidio. DREAM Program in Mozambique. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.dream-health.org/where-we-are/mozambique/?lang=en\u003c/span\u003e\u003cspan address=\"https://www.dream-health.org/where-we-are/mozambique/?lang=en\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. World Health Organization; 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeduzzi C, Pierotti P, Venturi G, et al. Performance of an in-house genotypic antiretroviral resistance assay in patients pretreated with multiple human immunodeficiency virus type 1 protease and reverse transcriptase inhibitors. J Clin Virol. 2002;25:57\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanters S, Vitoria M, Zoratti M et al. Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: a systematic literature review and network meta-analysis. \u003cem\u003eEClinicalMedicine\u003c/em\u003e; 28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePunekar Y, Parks D, Joshi M, et al. Effectiveness and safety of dolutegravir two-drug regimens in virologically suppressed people living with HIV: a systematic literature review and meta‐analysis of real‐world evidence. HIV Med. 2021;22:423\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFokam J, Inzaule S, Colizzi V, et al. HIV drug resistance to integrase inhibitors in low-and middle-income countries. Nat Med. 2024;30:618\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe International AIDS Society. Differentiated Service Delivery, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.differentiatedservicedelivery.org\u003c/span\u003e\u003cspan address=\"https://www.differentiatedservicedelivery.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiccacci F, Ismael F, Chume V et al. Enhancing retention in care in HIV-infected adolescents during COVID-19 in Mozambique: results from the DREAM program. Int J Adolesc Med Health. Epub ahead of print 2023. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1515/ijamh-2022-0107\u003c/span\u003e\u003cspan address=\"10.1515/ijamh-2022-0107\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFox MP, Pascoe S, Huber AN, et al. Adherence clubs and decentralized medication delivery to support patient retention and sustained viral suppression in care: Results from a cluster-randomized evaluation of differentiated ART delivery models in South Africa. PLoS Med. 2019;16:e1002874.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKouamou V, Manasa J, Katzenstein D, et al. Drug resistance and optimizing dolutegravir regimens for adolescents and young adults failing antiretroviral therapy. Aids. 2019;33:1729\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLong L, Kuchukhidze S, Pascoe S, et al. Retention in care and viral suppression in differentiated service delivery models for HIV treatment delivery in sub-Saharan Africa: a rapid systematic review. J Int AIDS Soc. 2020;23:e25640.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTriulzi I, Ciccacci F, Palla I et al. Improving Male Partner Involvement in HIV-Positive Women\u0026rsquo;s Care Through Behavioral Change Interventions in Malawi (WeMen Study): A Prospective, Controlled Before-and-After Study. \u003cem\u003eFrontiers in Public Health\u003c/em\u003e; 10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHlongwa M, Moyo E, Dzinamarira T. Approaches for improving linkage to HIV care among HIV self-testing individuals in sub-Saharan Africa. BMJ Global Health. 2023;8:e012664.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTerefe B, Jembere MM, Reda GB, et al. Knowledge, and utilization of HIV self-testing, and its associated factors among women in sub\u0026ndash;Saharan Africa: evidence from 21 countries demographic and health survey. BMC Public Health. 2024;24:1960.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrlando S, Marazzi MC, Mancinelli S, et al. Cost-effectiveness of using HAART in prevention of mother-to-child transmission in the DREAM-Project Malawi. JAIDS J Acquir Immune Defic Syndr. 2010;55:631\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrlando S, Triulzi I, Ciccacci F, et al. Delayed diagnosis and treatment of tuberculosis in HIV\u0026thinsp;+\u0026thinsp;patients in Mozambique: A cost-effectiveness analysis of screening protocols based on four symptom screening, smear microscopy, urine LAM test and Xpert MTB/RIF. PLoS ONE. 2018;13:e0200523.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiapka M, Remme M, Obure CD, et al. Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low-and middle-income countries. Bull World Health Organ. 2014;92:499\u0026ndash;AD511.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarkar S, Corso P, Ebrahim-Zadeh S, et al. Cost-effectiveness of HIV prevention interventions in sub-Saharan Africa: a systematic review. EClinicalMedicine. 2019;10:10\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMody A, Sohn AH, Iwuji C, et al. HIV epidemiology, prevention, treatment, and implementation strategies for public health. Lancet. 2024;403:471\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"aids-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arty","sideBox":"Learn more about [AIDS Research and Therapy](http://aidsrestherapy.biomedcentral.com/)","snPcode":"12981","submissionUrl":"https://submission.nature.com/new-submission/12981/3","title":"AIDS Research and Therapy","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"HIV, Drug Resistance, Viral, HIV Integrase Inhibitors, Antiretroviral Therapy, Highly Active, Africa, Public Health Surveillance","lastPublishedDoi":"10.21203/rs.3.rs-5676736/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5676736/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eIntroduction\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe global HIV epidemic remains a public health challenge. Dolutegravir (DTG) has become a cornerstone of antiretroviral therapy (ART) regimens due to its efficacy and tolerability. However, the emergence of DTG resistance is a concern. This study aims to evaluate virological outcomes and the emergence of resistance mutations in patients treated with DTG in Mozambique.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA retrospective cohort study was conducted in seven DREAM centers in Mozambique. Data were collected from electronic medical records of patients on DTG-based ART between July-2022 and December-2023. Virological suppression rates, patient demographics and clinical characteristics, and the prevalence of resistance mutations were analyzed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 29,601 patients were included, 98.1% (29,051 patients) were on DTG-based ART. The overall virological suppression rate among patients on DTG was 95% (27,622/29,051). Multivariate logistic regression analysis identified the following factors independently associated with virological suppression: older patients (aged\u0026thinsp;\u0026gt;\u0026thinsp;50 years) had higher odds of achieving virological suppression (OR: 2.45, 95% CI: 1.85\u0026ndash;3.26, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), longer duration on ART (\u0026gt;\u0026thinsp;5 years) was also associated with suppression (OR: 1.92, 95% CI: 1.44\u0026ndash;2.58, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), female patients had higher odds of suppression (OR: 0.85, 95% CI: 0.75\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.02), and patients treated in Quelimane City had lower odds of suppression compared to those in Machava (OR: 0.67, 95% CI: 0.52\u0026ndash;0.86, p\u0026thinsp;=\u0026thinsp;0.01). Of the 74 samples sent for resistance testing, 17 were analyzed for DTG resistance, and 8 displayed resistance major mutations. The most common mutations identified were G118R and E138K, variably associated with other major mutations.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study demonstrates the effectiveness of DTG within the DREAM program in Mozambique, with a high rate of virological suppression. However, the emergence of resistance mutations underscores the need for ongoing monitoring and surveillance to optimize treatment outcomes and preserve the efficacy of DTG.\u003c/p\u003e","manuscriptTitle":"Virological Outcomes and Dolutegravir Resistance Mutations in HIV-infected Patients: A Multicenter Retrospective Cohort Study in Mozambique","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-25 16:02:40","doi":"10.21203/rs.3.rs-5676736/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-20T05:06:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-12-19T19:44:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-12-19T12:53:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"AIDS Research and Therapy","date":"2024-12-19T12:11:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"aids-research-and-therapy","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arty","sideBox":"Learn more about [AIDS Research and Therapy](http://aidsrestherapy.biomedcentral.com/)","snPcode":"12981","submissionUrl":"https://submission.nature.com/new-submission/12981/3","title":"AIDS Research and Therapy","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"658af0df-2539-4b75-9644-b504564f83dc","owner":[],"postedDate":"December 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:08:39+00:00","versionOfRecord":{"articleIdentity":"rs-5676736","link":"https://doi.org/10.1186/s12981-025-00708-w","journal":{"identity":"aids-research-and-therapy","isVorOnly":false,"title":"AIDS Research and Therapy"},"publishedOn":"2025-01-30 15:57:29","publishedOnDateReadable":"January 30th, 2025"},"versionCreatedAt":"2024-12-25 16:02:40","video":"","vorDoi":"10.1186/s12981-025-00708-w","vorDoiUrl":"https://doi.org/10.1186/s12981-025-00708-w","workflowStages":[]},"version":"v1","identity":"rs-5676736","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5676736","identity":"rs-5676736","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}