Prevalence of acquired and transmitted HIV drug resistance in Iran: A systematic review and Metaanalysis

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Therefore, this investigation aimed to estimate the prevalence of HIVDR among antiretroviral therapy (ART) naïve people (those without a history of ART) and people receiving ART. Method We systematically searched Scopus, PubMed, Web of Science, Embase, Iranian database, the references of studies, and google scholar till March, 2023. A random-effect model was implemented to calculate point estimate and 95% confidence interval (95% CI) for the prevalence of HIVDR in people living with HIV (PLHIV). Results Among 461 potential publications, 22 studies were included in the meta-analysis. The pooled prevalence of acquired HIVDR in people receiving ART was 34.0% (95% CI: 19.0%-50.0%) for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 27.0% (95% CI: 15.0% -41.0%) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 9.0% (95% CI: 3.0% -18.0%) for protease inhibitors (PIs). The pooled prevalence of Acquired HIVDR in treatment failure PLHIV was 50.0% (95% CI: 31.0% − 69.0%) for NRTI, 49.0% (95% CI: 29.0%-69.0%) for NNRTI, 11.0% (95% CI: 2.0% − 24.0%) for PI, and 1.0% (95% CI: 0–4.0%) for integrase inhibitors (INIs). The pooled prevalence of transmitted HIVDR in treatment naïve people was 3.0% (95% CI; 1.0%-6.0%) for NRTI, 5.0% (95% CI: 2.0%-9.0%) for NNRTI, and 0 for PIs and INIs. Conclusion The prevalence of HIVDR in Iranian treatment naïve and people receiving ART was relatively high. Without universal pretreatment HIVDR testing and more frequent routine viral load testing among PLHIV who are on ART, these numbers may go up. Anti-Retroviral Agents Drug Resistance Drug Resistance Viral HIV Infections Treatment Failure Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Global access to antiretroviral therapy (ART) has been increased significantly. By the end of 2019, 25.4 million (67%) of the 38.0 million people living with HIV were on antiretroviral therapy, a number that has more than tripled since 2010. Almost 59% of PLHIV had suppressed viral loads (1). Remarkable progress has been made in reducing mortality, improving quality of life and life expectancy in PLHIV due to increased access to ART. Increased access to antiretroviral therapies also resulted in a 39% reduction in AIDS-related death from 2010 to 2019 (1). Widespread use of ART accompanied by the emergence of HIV drug resistance (HIVDR). HIVDR occurred due to mutation in the genetic structure of HIV viruses that affects the ability of drugs to inhibit the virus replication. These mutations can occur during the viral replication in individuals receiving ART (Acquired HIVDR) or when suseptible individuals are infected with drug-resistant viruses (Transmitted HIVDR). Transmitted HIVDR is being measured in PLHIV with no history of ART (ART naïve)(2). The high prevalence of HIVDR threatens the public health response to the HIV treatment and attainment of the global targets to end the HIV epidemic. In fact, monitoring the drug resistnace patterns and prevlance, by routine viral load or HIV drug resistance testing is one of the five startegies recommeded by World Health Organization to prevent from HIV drug resistance. (3). In Iran, 59,314 people are estimated to live with HIV in 2019; 22,054 (37.2%) people know their HIV status, and 14,685 (66.5% of those who were aware of their status) people are on ART (4). The most common ARTs in Iran are nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and the relatively new integrase inhibitors (INI) (5). While HIV drug resistance testing for everyone who want to start treatmet has been demonstrated to have clinical benefits (6, 7), the HIV treatemtn program in Iran is not able to do so for all people diagnosed with HIV. The current national guideline recommend HIV drug resistance testing for those who failed to achieve suppressed viral load at 6 months after starting treatment (5); however, also for this subgroup, the HIV drug resistance testing has not been done universally due to costs and limited lab capacities (8) . Therefore, this investigation aimed to conduct a systematic review and meta-analysis to generate pooled estimates of HIV drug resistance prevalence among ART naïve individuals and people receiving ART. Method This study was conducted following the Systematic Reviews and Meta-Analyses (PRISMA) checklist (see Supplementary File S1) and the Peer Review of Electronic Search Strategies. The details of the search, inclusion criteria, and the analytic plan is available in Open Science Framework (osf.io/vxpe5). Search strategy We systematically searched international (including Scopus, PubMed, Web of Science, and Embase) and Iranian databases (including Iranian Medical Research Information System ( https://research.ac.ir/ ) , Magiran https://www.magiran.com/ , and Scientific Information Database: https://www.sid.ir/ ) for studies published in English and Persian. We also reviewed the reference list of eligible studies till March, 2023. The following terms included (HIV, human immunodeficiency virus, AIDS, acquired immunodeficiency syndrome) AND (antiviral drug resistance, drug resistance, resistance, mutation, drug resistance mutation) in databases were searched in English and Persian. Search terms were combined using appropriate Boolean operators (Supplementary File S2). Screening After excluding duplicate citations, studies were screened based on their title and abstract. Full-text of the eligible citations were evaluated for inclusion and exclusion criteria at this stage. Two reviewers (HM and FM) did the screening process, and disagreements were resolved by discussing two individuals and consulting with the senior author (HSH). Inclusion and exclusion criteria Community-based cross-sectional or cohort studies that evaluated HIV drug resistance prevalence among HIV-infected individuals were included. Studies were excluded if used from data of gene banks or information of medical records of HIV infected individuals. Data extraction We extracted the following variables: first author, publication year, study period, treatment status (people receiving ART or treatment naïve), study location (city and province), sample size, number of mutations, and type of mutations. Risk of bias The Joanna Briggs Institute’s critical appraisal tool for prevalence studies was used to assess the methodological quality of the included papers. This tool had nine items to evaluate sample size and representativeness of sampling, identification of the condition, description of the study participants, statistical analysis, and managing response rate. Two independent reviewers assessed the methodological quality of the included studies (HM and FM). Disagreements were resolved through discussion and consultation with the senior author (Supplementary File S3). Statistical analysis Point estimate and 95% Confidence Intervals (95% CI) for the prevalence of HIV drug resistance were estimated for the treatment-naïve and people on ART. Heterogeneity between studies was assessed using the I 2 statistic. Random effect meta-analysis was performed as the I 2 statistic was more than 50%, representing substantial heterogeneity. Subgroup analysis was conducted based on each drug groups (NRTI, NNRTI, PI, and INI). Also, we performed subgroup analysis based on treatment status (all people receiving ART or individuals with treatment failure) of people on ART. Results This review identified 461 potential publications on HIV drug resistance in Iran. After excluding duplicates (156 studies) and unrelated titles and abstracts (272 studies), 33 full texts were evaluated for eligibility, among which 11 studies were excluded. Finally, 22 eligible citations were included in the meta-analysis (Fig. 1 ). Of 22 included studies, 9 were conducted on people receiving ART, 6 on HIV treatment naïve individuals, and 7 were on a mixed sample of ART naïve and people receiving ART. Studies were conducted in Tehran (n = 9), Bandar Abbas, Shiraz (each = 2), Sanandaj, Gorgan, and Ahvaz (each = 1). Also, six studies enrolled people from more than one city. All studies had a cross-sectional design. Fourteen studies focused on the prevalence of resistance to three drug groups, including NRTI, NNRTI, and PI, while three studies focused on resistance to PI, one study focused on INIs, and one focused on NRTI, NNRTI, and INIs. The largest sample size was 655, and the smallest was 25 individuals (Table 1 ). The quality score of the included studies ranged from five to nine (out of nine scores) (Supplementary File S3). Table 1 Characteristics of studies included in the meta-analysis of HIV drug resistance prevalence in Iran Study Study type Study Period Study group Province- City Sample Size Evaluated drugs Successful Sequences Marjani 2020(21) Cross-sectional June 2012 to December 2018 People receiving ART Tehran 655 integrase region 62 Bokharaei, 2020(22) Cross-sectional April 2013 to September 2018 ART naïve and People receiving ART Tehran 60 naïve, 592 people receiving ART NRTI, NNRTI, And PI 60 Mohraz, 2019(23) Cross-sectional December 2015 and May 2016 People receiving ART 11 Cities (Tehran, Qom, Esfahan, Gilan, Kermanshah, Ahvaz, Bandar abbas, Khorramabad, Karaj, Kerman, Hamedan) 207 NRTI, NNRTI, And PI 78 Memarnejadian, 2019(24) Cross-sectional April 2016 to March 2017 People receiving ART Bandar Abbas 44 NRTI, NNRTI, And PI 44 Farrokhi, 2019(25) ART naïve Tehran, Kermanshah, Esfahan, Shiraz, Mashhad, Gilan, bandar abbas, Ahvaz 105 NRTI, NNRTI, And PI 90 Nasiri-Tajabadi, 2018(26) People receiving ART, ART naïve Tehran, Mashhad 25 25 PI 25 25 Memarnejadian, 2018(27) Cross sectional April 2016 and March 2017 ART naïve Bandar abbas 41 NRTI, NNRTI, And PI 41 Ghafari, 2018(28) Cross-sectional March 2014 to February 2015 ART naïve Ahvaz 52 NRTI, NNRTI, And PI 52 Vahabpour,2017(29) Cross-sectional September 2015 and July 2016. ART naïve Tehran 42 NRTI, NNRTI, And PI 42 Farrokhi(30) Cross-sectional People receiving ART, ART naïve Tehran 50 28 NRTI, NNRTI, And PI 50 28 Naziri, 2016(31) Cross-sectional April 2013 to February 2014 People receiving ART, ART naïve Shiraz 62 40 NRTI, NNRTI, And PI 62 40 Baesi, (32) People receiving ART Tehran 25 PI 25 Memarnejadian,2015(33) Cross sectional 2011 ART- naïve Sanandaj 40 NRTI, NNRTI, And PI 40 Gol Mohammadi, 2015(34) Cross-sectional People receiving ART Gorgan 130 NRTI and NNRTI 122 Baesi, 2014(35) Cross-sectional People receiving ART, ART- naïve Tehran 70 30 NRTI, NNRTI, And PI 62 62 Jahanbakhsh, 2013(36) Cross-sectional January 2010 to February 2011 ART- naïve Tehran, Kermanshah and Shiraz 50 NRTI, NNRTI, And PI 47 Baesi, 2012(37) Cross-sectional ART- naïve People receiving ART Tehran 30 16 PI 30 15 Baesi,2012(38) Cross-sectional People receiving ART Tehran 25 NRTI and NNRTI 24 Naziri, 2013 (39) Cross-sectional Not reported ART- naïve People receiving ART Shiraz 20 20 NRTI, NNRTI, And PI 20 20 Hamkar, 2010(40) Cross-sectional People receiving ART Tehran 42 NRT, NNRTI, And PI 42 Gholami, 2020(41) Cross-sectional People receiving ART Tehran, Khorramabad, Qom, Ahvaz, and Hamedan 41 NNRTI, NNRT, PI, and INTI 41 Mousavi, 2010 (42) Cross-sectional People receiving ART Tehran, Khorramabad, Ahvaz, qom, Hamedan 33 NRT, NNRTI, PI, and INIs Prevalence Of Acquired Hiv Drug Resistance The pooled prevalence of acquired HIVDR among people receiving ART was 34.0% (95% CI: 19.0%-50.0%, I 2 = 96.5%) for NRTIs, 27.0% (95% CI: 15.0% -41.0%, I 2 = 95.2%) for NNRTIs, and 9.0% (95% CI: 3.0% -18.0%, I 2 = 92.6%) for PIs, and zero for INIs. There was a high degree of heterogeneity among studies in all subgroups (I 2 > 90%) (Fig. 2 ). The pooled prevalence of acquired HIVDR in PLHIV with treatment-failure was 50.0% (95% CI: 31.0% − 69.0%, I 2 = 89.7%) for NRTIs, 49.0% (95% CI: 29.0%-69.0%, I 2 = 90.9%) for NNRTIs, 11.0% (95% CI: 2.0% − 24.0%, I 2 = 88.1%) for PIs, and 1.0% (95% CI: 0–4.0%, I 2 = 0) for INIs (Fig. 3 ). Among on treatement PLHIV with resistance to NRTI drugs, the most common mutations were M184V/I (56.4%), T215Y/N/S/F/I (21.3%), and K219E/Q/R (19.0%). Among the patients with resistance to NNRTI drugs, the most common mutations were K103k/N/S/E (52.2%), P225H (16.1%), and Y181C/S (9.2%). Among the patients with resistance to PI drugs, the most common mutations were V82A/I/M/C (29.0%), M46I (27.4%), and L90M (16.1%) (Table 2 ). Table 2 Frequency of acquired HIV drug resistance mutations NRTI Mutations NNRTI Mutations Pi Mutations Mutation Frequency (%) of 211 Mutation Frequency (%) = 184 Mutation Frequency (%) N = 62 M184V/I 119 (56.4%) K103k/N/S/E 96 (52.2%) V82A/I/M/C 18 (29.0%) T215Y/N/S/F/I 45 (21.3%) P225H 31 (16.1%) M46I 17 (27.4%) K219E/Q/R 40 (19.0%) M230L 17 (9.2%) L54V/L 11 (17.7%) V75M/C/A 35 (16.6%) Y181C/S 17 (9.2%) L90M 10 (16.1%) M41L 26 (12.3%) V108i 15 (8.15%) L50V/L 9 (14.5%) D67N/G/Q 23 (10.9%) K101Ekqr 13 (7.1%) V32i 6 (9.7%) K70R/T/I/E/Q 21 (10.0%) E138A/G 13 (7.1%) L76v 2 (3.2%) T69S/N/P/I 11 (5.2%) V179tf 11 (6.0%) I84v 2 (3.2%) K65R/E/I/N/G 11 (5.2%) K238tn 8 (4.3%) F77L/C 5 (2.4%) A98g 8 (4.3%) L74V/I 5 (2.4%) V106mia 5 (2.7%) Y115F 1 (0.5%) H221Y 3 (1.6%) L100v 2 (1.1%) P236l 1 (0.5%) N348i 1 (0.5%) Prevalence Of Transmitted Hiv Drug Resistance The pooled prevalence of transmitted HIVDR in treatment naïve individuals was 3.0% (95% CI; 1.0%-6.0%, I 2 = 38.1%) for NRTI, 5.0% (95% CI: 2.0%-9.0%, I 2 = 60.2%) for NNRTI, and 0 for PI and INI. There was a medium degree of heterogeneity among studies in all subgroups (I 2 = 54.0%) (Fig. 4 ). Among teatment-naive PLHIV with resistance to NRTI drugs, the most common mutations were T215Y/N/S/F/I (55.0%), M184V/I (30.0%), and M41L (25.0%). Among the patients with resistance to NNRTI drugs, the most common mutations were K103k/N/S/E (45.7%), E138A/G (28.6%), and V179T/F (25.7%) (Table 3 ). Table 3 Frequency of transmitted HIV drug resistance mutation NRTI related Mutations NNRTI related Mutations PI related Mutations Mutation Frequency (%) of 20 Mutation Frequency N = 35 Frequency Mutation N = 4 T215Y/N/S/F/I 11 (55.0%) K103knse 16 (45.7%) M46I 2 (50.0%) M184V/I 6 (30.0%) E138A/G 10 (28.6%) L76V 2 (25.0%) M41L 5 (25.0%) V179T/F 9 (25.7%) G48V 2 (25.0%) D67ngq 4 (20.0%) V106mia 6 (17.1%) L50V/L 1 (12.4%) Y115F 3 (15.0%) Y181cs 4 (11.4%) K65reing 2 (10.0%) K101Ekqr 2 (5.7%) K70rtieq 2 (10.0%) P225h 2 (5.7%) V75M/A/S 2 (10.0%) K238tn 1 (2.9%) L210W 2 (10.0%) K219eqr 1 (5.0%) Discussion In this systematic review and meta-analysis, we investigated the pooled prevalence of resistance to NRTI, NNRI, and PI drugs in the treatment naïve and people receiving ART. The pooled prevalence of acquired HIVDR in PLHIV was 34.0% for NRTI, 27.0% for NNRTI, and 9.0% for PI. The prevalence of transmitted HIVDR in treatment-naive PLHIV was 3.0% for NRTIs, 5.0% for NNRTIs, and 0% for PIs and INIs. The pooled prevalence of acquired HIVDR in PLWH was 34.0% for NRTI, 27.0% for NNRTI, and 9.0% for PI that is higher than the available reports. WHO reported that in 2019, the prevalence of any HIVDR among all individuals receiving treatment ranged from 3.0% in Vietnam to 29.0% in Honduras (8). In our study, the prevalence of HIVDR to NNRTIs among populations for whom NNRTI-based first-line treatment failed was 49.0%; WHO reported that in 2019, the prevalence of NNRTI resistance in these people ranged from 50.0% in Eswatini to 97.0% in Uganda (8). The pooled prevalence of transmitted HIVDR in treatment naïve individuals was 3.0% for NRTI, 5.0% for NNRTI. Based on WHO report, pretreatment drug resistance to NNRTI was 7.8% among HIV-infected patients in 18 countries (8). There are four possible main reasons for higher prevalence of HIV drug resistance in Iran. First, the frequency of viral load testing in Iran is low. Studies showed that NNRTI-related HIV drug resistance was higher among individuals who monitored viral load less frequently than every three months than more frequently monitored patients (REF). Analysis of national data showed that among 14,685 people on ART in Iran, only 7,471 (50.9%) received viral load testing at least once in 2019 (4). In Iran’s national guidline for HIV treatment, viral load testing is recommeded for six months after the initiation of ART for the first time and for every 12 months after. Second, low quality of HIVDR monitoring and surveillance in Iran. WHO reported that quality-of-care indicators associated with the emergence of HIVDR (including retention on ART at 12 months, viral load testing coverage, viral load suppression at 12 months, drug stock-out, and proportion of people on second-line ART) in Iran are not satisfactory (8). Third, low adherence to ART among PLHIV (9). ART adherence in Iran in previous studies ranged from 54.4–85.0% (10, 11). Fourth, since the self-medication of drugs in Iran is high (67%) (12, 13), drug-drug interaction with other medicines including antibiotics, herbal medicine, or even sedatives can be another reason for the high prevalence of HIV drug resistance (14, 15). The most common NRTI resistance mutation was M184V/I, reducing susceptibility to 3TC (lamivudine)/FTC (Emtricitabine). The most common NNRTI resistance mutation was K103k/N/S/E which reduces susceptibility to NVP (nelfinavir) and EFV(efavirenz); the most common PI resistance mutation was M46I and V82A/I/M/C, which reduces susceptibility to IDV (indinavir), NFV (nelfinavir), FPV, ATV (Atazanavir), and LPV (lopinavir)(16). High prevalence of resistance to these drugs can be due to the higher consumption in Iran. The initial drug regimens for PLHIV in Iran before the 2020 was two NRTI (Tenofovir + Emtricitabine OR Tenofovir + Emtricitabine OR Tenofovir + Lamivudine) and one NNRTI (Efavirenz). In the latest treatment guideline in Iran, the initial drug regimen changed to one INI (Dolutegravir) and two NRTI. Information about common HIV drug resistance mutations can be used to adopt a new drug as the preferred first-line treatment. Understanding the reasons for HIVDR is crucial for a better response to this issue. To prevent and respond to HIVDR in Iran, in the latest national guidelines for care and treatment of HIV, the preferred first-line drug for the treatment of HIV changed to Dolutegravir-based antiretroviral regimens (5). This intervention can help prevent HIVDR because Dolutegravir has a high genetic barrier to the resistance (17). Unfortunately, programmatic quality indicators for the HIVDR surveillance in Iran are unsatisfactory (8). Therefore, emphasizing the standardized HIVDR surveys based on WHO guidelines is necessary. Another strategy for monitoring HIVDR is to add routine pretreatment HIVDR testing in the national HIV program to guide regimen selection (3). Studies showed that pretreatment HIVDR testing could improve clinical outcomes. This strategy is currently standard practice in high-income countries (18). A study in Brazil suggests that pretreatment HIVDR testing is a cost-savings task (19), but a study in Kenya showed that it was not cost-effective (20). The cost-effectiveness of new interventions depends on the prevalence of the related problem, availability of resources, and effectiveness thresholds (18). All these suggested the need for cost-effectiveness analysis of pretreatment HIVDR testing in Iran. Limitations Our study hsd three main limitations. First, there was a high degree of heterogeneity among included studies. By analyzing data in treatment groups (treatment naïve, total people receiving ART, and treatment failure people), heterogeneity decreased in treatment naïve people, yet it was high in people receiving ART. Second, HIVDR in those who were on treatemet could have been resulted from tranissmission of a drug resistance virus, which we were not able to diffrentiate. Third, included studies have not reported the prevalence of drug resistance by key populations at high risk for HIV (e.g., female sex worker, people who inject drugs, male sex with male). Conclusion Based on the results of this systematic review prevalence of HIVDR in Iranian treatment naïve and people receiving ART was relatively high. Without universal pretreatment HIVDR testing and more frequent routine viral load testing among PLHIV on ART, these numbers may go up., Providing Dolutegravir based drugs may prevent from transmission of HIVDR mutations. All of these interevetions should also monitoried by a high quality monitoring and surveillnce syatem. Abbreviations HIVDR: HIV drug resistance ART: antiretroviral therapy PLHIV: people living with HIV CI: confidence interval NRTI: nucleoside/nucleotide reverse transcriptase inhibitors NNRTI: non-nucleoside reverse transcriptase inhibitors PI: protease inhibitors INI: integrase inhibitors Declarations Authors’ contributions All authors met the criteria for authorship as established by the International Committee of Medical Journal Editors. Contributions were as follows: HM: Keywords extraction, design search strategy, literature search, literature review, analysis of data, drafting, and critical revisions of the manuscript. SE: design search strategy, literature search, literature review, analysis of data, critical revisions of the manuscript. FM: Keywords extraction, design search strategy, literature review, data abstraction, critical revisions of the manuscript. MRSH: Keywords extraction, literature review, data abstraction, critical revisions of the manuscript. AM: Keywords extraction, design search strategy, literature search, Analysis of data, critical revisions of the manuscript. HSH: Keywords extraction, design search strategy, literature search, literature review, Analysis of data drafting, and critical revisions of the manuscript. MKH: literature review, data abstraction, critical revisions of the manuscript. NN: literature search, literature review, data abstraction, critical revisions of the manuscript Conflicts of interest There are no conflicts of interest. Acknowledgements This article is part of a Ph.D. thesis supported by the Kerman University of Medical Sciences (Grant number: 99000587). Funding This work was supported by Kerman University of Medical Sciences Availability of data materials All data generated and analyzed during this study are included in this review. Ethical approval and consent to participate Not applicable. 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EClinicalMedicine. 2020;22:100355 Marjani A, Bokharaei-Salim F, Jahanbakhshi F, Monavari SH, Esghaei M, Kalantari S, et al. HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients. Arch Virol. 2020;165(1):115-25.10.1007/s00705-019-04463-y Bokharaei-Salim F, Esghaei M, Khanaliha K, Kalantari S, Marjani A, Fakhim A, et al. HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naive HIV-infected individuals. Plos One. 2020;15(3):15.10.1371/journal.pone.0229275 Mohraz M, Tayeri K, Tabar HN, Jozani ZB, Sadeghi L, SeyedAlinaghi S, et al. Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9-15 Months in 14 Triangular Clinics in Iran, 2015-2016. Intervirology. 2019;61(6):292-300.10.1159/000497036 Memarnejadian A, Nikpoor AR, Davoodian N, Kargar A, Mirzadeh Y, Gouklani H. 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Prevalence of HIV-1 transmitted drug resistance in recently infected, treatment-naive persons in the Southwest of Iran, 2014-2015 (vol 162, pg 2737, 2017). Arch Virol. 2018;163(1):297-.10.1007/s00705-017-3669-6 Vahabpour R, Bokharaei-Salim F, Kalantari S, Garshasbi S, Monavari SH, Esghaei M, et al. HIV-1 genetic diversity and transmitted drug resistance frequency among Iranian treatment-naive, sexually infected individuals. Arch Virol. 2017;162(6):1477-85.10.1007/s00705-017-3228-1 Farrokhi M, Moallemi S, Baesi K, Ahsani-Nasab S, Gholami M, Sadeghi L, et al. HIV Drug Resistance and Phylogeny Profile in Naïve and Antiretroviral-Experienced Patients in Tehran, Iran. Intervirology. 2017;59(3):131-6.10.1159/000452712 Naziri H, Baesi K, Moradi A, Aghasadeghi MR, Tabarraei A, McFarland W, et al. Antiretroviral drug resistance mutations in naive and experienced patients in Shiraz, Iran, 2014. Arch Virol. 2016;161(9):2503-9.10.1007/s00705-016-2955-z Baesi K, Moradbeigi M, Ravanshad M, Baghban A. Phylogeny and drug resistance of HIV PR gene among HIV patients receiving RT inhibitors in Iran. Asian Pac J Trop Biomed. 2016;6(5):451-4.10.1016/j.apjtb.2015.12.020 Memarnejadian A, Menbari S, Mansouri SA, Sadeghi L, Vahabpour R, Aghasadeghi MR, et al. Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug Users with Chronic HIV-1 Infection in Iran. Plos One. 2015;10(5):9.10.1371/journal.pone.0126955 Mohammadir G, Tabaraeia, Abbasia, Khademin, Mahdavianb, Javidn, et al. Drug-Resistant HIV-1 RT Gene Mutations in Patients under Treatment with Antiretroviral Drugs (HAART) in Iran. Med Lab J. 2015;9(1):1 Baesi K, Ravanshad M, Ghanbarisafari M, Saberfar E, SeyedAlinaghi S, Volk JE. Antiretroviral drug resistance among antiretroviral-naive and treatment experienced patients infected with HIV in Iran. J Med Virol. 2014;86(7):1093-8.10.1002/jmv.23898 Jahanbakhsh F, Hattori J, Matsuda M, Ibe S, Monavari SH, Memarnejadian A, et al. Prevalence of transmitted HIV drug resistance in Iran between 2010 and 2011. PLoS One. 2013;8(4):e61864.10.1371/journal.pone.0061864 Baesi K, Ravanshad M, Ghanbari Safari M, Saberfar E, Hajiabdolbaghi M. Drug Resistance of HIV-1 protease gene among AIDS patients in Iranian research center for AIDS. Pathobiology Reaearch. 2012;14(4):14 Baesi K, Ravanshad M, Hosseini Y, Abdolbaghi MH. Drug resistance profile and subtyping of HIV-1 RT gene in Iranian patients under treatment. Iran J Biotechnol. 2012;10(1):1-7 Naziri h, Tabarraei a, Ghaemi a, Davarpanah m, Javid a, Moradi a. Drug-resistance-associated mutations and hiv sub-type determination in drug-naive and hiv-positive patients under treatment with antiretroviral drugs. Med Lab J. 2013;7(3):- Hamkar R, Mohraz M, Lorestani S, Aghakhani A, Truong H-HM, McFarland W, et al. Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. AIDS. 2010;24:S85-S91.10.1097/01.aids.0000386738.32919.67 Gholami M, Rouzbahani N, Samiee S, Tayeri K, Ghorban K, Dehkharghani AD, et al. HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. Microb Pathog. 2020;146:8.10.1016/j.micpath.2020.104221 Mousavi SM, Hamkar R, Gouya MM, Safaie A, Zahraei SM, Yazdani Z, et al. Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study. Arch Virol. 2010;155(3):329-34.10.1007/s00705-009-0583-6 Additional Declarations No competing interests reported. Supplementary Files SupplementaryfileS1PRISMAChecklist.docx SupplementaryFileS2Searchstrategies.docx SupplementaryFileS3Riskofbias.docx Cite Share Download PDF Status: Published Journal Publication published 02 Jan, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Major revision 15 Sep, 2023 Reviews received at journal 01 Sep, 2023 Reviewers agreed at journal 24 Aug, 2023 Reviewers invited by journal 24 Aug, 2023 Editor assigned by journal 24 Aug, 2023 Editor invited by journal 09 Apr, 2023 Submission checks completed at journal 09 Apr, 2023 First submitted to journal 01 Apr, 2023 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2766057","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":190297060,"identity":"224ee6ca-5723-4d38-b33e-b40aadd64f32","order_by":0,"name":"Hossein Mirzaei","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hossein","middleName":"","lastName":"Mirzaei","suffix":""},{"id":190297061,"identity":"7f2e72f9-dfca-4efc-85d7-a026a148fb50","order_by":1,"name":"Sana Eybpoosh","email":"","orcid":"","institution":"Pasteur Institute of Iran","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sana","middleName":"","lastName":"Eybpoosh","suffix":""},{"id":190297062,"identity":"07a6c757-274c-45a6-9a16-c3edac317dd0","order_by":2,"name":"Fatemeh Mehrabi","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Mehrabi","suffix":""},{"id":190297063,"identity":"56712a01-99e6-46eb-80f4-d06c92db61f7","order_by":3,"name":"Mohammad Reza Shojaei","email":"","orcid":"","institution":"Kerman University of Medical Science","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Reza","lastName":"Shojaei","suffix":""},{"id":190297064,"identity":"6121e46f-5747-463c-b38f-b2627ff6be2b","order_by":4,"name":"Ali Mirzazadeh","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"Mirzazadeh","suffix":""},{"id":190297065,"identity":"15cd6399-7ed5-4360-9550-f317e8546134","order_by":5,"name":"Mehrdad Khezri","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehrdad","middleName":"","lastName":"Khezri","suffix":""},{"id":190297066,"identity":"4506d956-29fe-4433-af35-d6a89c590aae","order_by":6,"name":"Naser Nasiri","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Naser","middleName":"","lastName":"Nasiri","suffix":""},{"id":190297067,"identity":"a90db664-9680-482e-bb8b-64ab3efa77dc","order_by":7,"name":"Hamid 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20:29:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2766057/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2766057/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-023-08916-3","type":"published","date":"2024-01-02T15:00:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":35592759,"identity":"877ad6c0-5a04-42a7-8ba1-b106ff6994a4","added_by":"auto","created_at":"2023-04-11 15:06:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39973,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2766057/v1/8ca9a70d3bc1f9a573b05f1e.png"},{"id":35591026,"identity":"afc0a8f2-a2e1-458b-b102-7a12f2ac7ace","added_by":"auto","created_at":"2023-04-11 14:50:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1345946,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of drug resistance in people living with HIV who were under the anti-retroviral treatment in Iran\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2766057/v1/61b42478e4a63d375bbe21fe.png"},{"id":35591030,"identity":"4e32cc01-54c8-4704-907c-9729f7ac8c23","added_by":"auto","created_at":"2023-04-11 14:50:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1314431,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of drug resistance in people living with HIV mutation in Iranian treatment failure HIV infected patients\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-2766057/v1/f25e3a8d46282ca7b3024dd2.png"},{"id":35591850,"identity":"ad5c31f4-8d8e-4752-a9fb-87345c006900","added_by":"auto","created_at":"2023-04-11 14:58:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1441917,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of drug resistance among naïvepeople living with HIV in Iran\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-2766057/v1/c219f2bf41b6518640389042.png"},{"id":49315743,"identity":"8beb865b-586a-4761-9953-8a53a2f27a6d","added_by":"auto","created_at":"2024-01-08 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14:58:30","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":14600,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFileS2Searchstrategies.docx","url":"https://assets-eu.researchsquare.com/files/rs-2766057/v1/139f3977d5089f37879534f6.docx"},{"id":35591031,"identity":"a2c3274a-1674-4335-8060-6fae09ba4b5f","added_by":"auto","created_at":"2023-04-11 14:50:30","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":19103,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFileS3Riskofbias.docx","url":"https://assets-eu.researchsquare.com/files/rs-2766057/v1/f85202556f5c0f0bc145bf48.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence of acquired and transmitted HIV drug resistance in Iran: A systematic review and Metaanalysis","fulltext":[{"header":"Background","content":"\u003cp\u003eGlobal access to antiretroviral therapy (ART) has been increased significantly. By the end of 2019, 25.4\u0026nbsp;million (67%) of the 38.0\u0026nbsp;million people living with HIV were on antiretroviral therapy, a number that has more than tripled since 2010. Almost 59% of PLHIV had suppressed viral loads (1). Remarkable progress has been made in reducing mortality, improving quality of life and life expectancy in PLHIV due to increased access to ART. Increased access to antiretroviral therapies also resulted in a 39% reduction in AIDS-related death from 2010 to 2019 (1).\u003c/p\u003e \u003cp\u003eWidespread use of ART accompanied by the emergence of HIV drug resistance (HIVDR). HIVDR occurred due to mutation in the genetic structure of HIV viruses that affects the ability of drugs to inhibit the virus replication. These mutations can occur during the viral replication in individuals receiving ART (Acquired HIVDR) or when suseptible individuals are infected with drug-resistant viruses (Transmitted HIVDR). Transmitted HIVDR is being measured in PLHIV with no history of ART (ART na\u0026iuml;ve)(2). The high prevalence of HIVDR threatens the public health response to the HIV treatment and attainment of the global targets to end the HIV epidemic. In fact, monitoring the drug resistnace patterns and prevlance, by routine viral load or HIV drug resistance testing is one of the five startegies recommeded by World Health Organization to prevent from HIV drug resistance. (3).\u003c/p\u003e \u003cp\u003eIn Iran, 59,314 people are estimated to live with HIV in 2019; 22,054 (37.2%) people know their HIV status, and 14,685 (66.5% of those who were aware of their status) people are on ART (4). The most common ARTs in Iran are nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and the relatively new integrase inhibitors (INI) (5). While HIV drug resistance testing for everyone who want to start treatmet has been demonstrated to have clinical benefits (6, 7), the HIV treatemtn program in Iran is not able to do so for all people diagnosed with HIV. The current national guideline recommend HIV drug resistance testing for those who failed to achieve suppressed viral load at 6 months after starting treatment (5); however, also for this subgroup, the HIV drug resistance testing has not been done universally due to costs and limited lab capacities (8) .\u003c/p\u003e \u003cp\u003eTherefore, this investigation aimed to conduct a systematic review and meta-analysis to generate pooled estimates of HIV drug resistance prevalence among ART na\u0026iuml;ve individuals and people receiving ART.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThis study was conducted following the Systematic Reviews and Meta-Analyses (PRISMA) checklist (see Supplementary File S1) and the Peer Review of Electronic Search Strategies. The details of the search, inclusion criteria, and the analytic plan is available in Open Science Framework (osf.io/vxpe5).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy\u003c/h2\u003e \u003cp\u003eWe systematically searched international (including Scopus, PubMed, Web of Science, and Embase) and Iranian databases (including Iranian Medical Research Information System (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://research.ac.ir/\u003c/span\u003e\u003cspan address=\"https://research.ac.ir/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e)\u003c/span\u003e, Magiran \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.magiran.com/\u003c/span\u003e\u003cspan address=\"https://www.magiran.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, and Scientific Information Database: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sid.ir/\u003c/span\u003e\u003cspan address=\"https://www.sid.ir/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) for studies published in English and Persian. We also reviewed the reference list of eligible studies till March, 2023.\u003c/p\u003e \u003cp\u003eThe following terms included (HIV, human immunodeficiency virus, AIDS, acquired immunodeficiency syndrome) AND (antiviral drug resistance, drug resistance, resistance, mutation, drug resistance mutation) in databases were searched in English and Persian. Search terms were combined using appropriate Boolean operators (Supplementary File S2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eScreening\u003c/h2\u003e \u003cp\u003eAfter excluding duplicate citations, studies were screened based on their title and abstract. Full-text of the eligible citations were evaluated for inclusion and exclusion criteria at this stage. Two reviewers (HM and FM) did the screening process, and disagreements were resolved by discussing two individuals and consulting with the senior author (HSH).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eCommunity-based cross-sectional or cohort studies that evaluated HIV drug resistance prevalence among HIV-infected individuals were included. Studies were excluded if used from data of gene banks or information of medical records of HIV infected individuals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eWe extracted the following variables: first author, publication year, study period, treatment status (people receiving ART or treatment na\u0026iuml;ve), study location (city and province), sample size, number of mutations, and type of mutations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias\u003c/h2\u003e \u003cp\u003eThe Joanna Briggs Institute\u0026rsquo;s critical appraisal tool for prevalence studies was used to assess the methodological quality of the included papers. This tool had nine items to evaluate sample size and representativeness of sampling, identification of the condition, description of the study participants, statistical analysis, and managing response rate. Two independent reviewers assessed the methodological quality of the included studies (HM and FM). Disagreements were resolved through discussion and consultation with the senior author (Supplementary File S3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003ePoint estimate and 95% Confidence Intervals (95% CI) for the prevalence of HIV drug resistance were estimated for the treatment-na\u0026iuml;ve and people on ART. Heterogeneity between studies was assessed using the I\u003csup\u003e2\u003c/sup\u003e statistic. Random effect meta-analysis was performed as the I\u003csup\u003e2\u003c/sup\u003e statistic was more than 50%, representing substantial heterogeneity. Subgroup analysis was conducted based on each drug groups (NRTI, NNRTI, PI, and INI). Also, we performed subgroup analysis based on treatment status (all people receiving ART or individuals with treatment failure) of people on ART.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e This review identified 461 potential publications on HIV drug resistance in Iran. After excluding duplicates (156 studies) and unrelated titles and abstracts (272 studies), 33 full texts were evaluated for eligibility, among which 11 studies were excluded. Finally, 22 eligible citations were included in the meta-analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOf 22 included studies, 9 were conducted on people receiving ART, 6 on HIV treatment na\u0026iuml;ve individuals, and 7 were on a mixed sample of ART na\u0026iuml;ve and people receiving ART. Studies were conducted in Tehran (n\u0026thinsp;=\u0026thinsp;9), Bandar Abbas, Shiraz (each =\u0026thinsp;2), Sanandaj, Gorgan, and Ahvaz (each =\u0026thinsp;1). Also, six studies enrolled people from more than one city. All studies had a cross-sectional design. Fourteen studies focused on the prevalence of resistance to three drug groups, including NRTI, NNRTI, and PI, while three studies focused on resistance to PI, one study focused on INIs, and one focused on NRTI, NNRTI, and INIs. The largest sample size was 655, and the smallest was 25 individuals (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The quality score of the included studies ranged from five to nine (out of nine scores) (Supplementary File S3).\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\u003eCharacteristics of studies included in the meta-analysis of HIV drug resistance prevalence in Iran\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy Period\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProvince- City\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSample Size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEvaluated drugs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSuccessful\u003c/p\u003e \u003cp\u003eSequences\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarjani 2020(21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eJune 2012 to December 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eintegrase region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBokharaei, 2020(22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eApril 2013 to September 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART na\u0026iuml;ve and People receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60 na\u0026iuml;ve, 592 people receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMohraz, 2019(23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDecember 2015 and May 2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 Cities (Tehran, Qom, Esfahan, Gilan, Kermanshah, Ahvaz, Bandar abbas, Khorramabad, Karaj, Kerman, Hamedan)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemarnejadian, 2019(24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eApril 2016 to March 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBandar Abbas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFarrokhi, 2019(25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran, Kermanshah, Esfahan, Shiraz, Mashhad, Gilan, bandar abbas, Ahvaz\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasiri-Tajabadi, 2018(26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART, ART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran, Mashhad\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemarnejadian, 2018(27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eApril 2016 and March 2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBandar abbas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGhafari, 2018(28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMarch 2014 to February 2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAhvaz\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVahabpour,2017(29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSeptember 2015 and July\u003c/p\u003e \u003cp\u003e2016.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\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\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFarrokhi(30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART, ART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e50\u003c/p\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNaziri, 2016(31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eApril 2013 to February 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART, ART na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eShiraz\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62\u003c/p\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e62\u003c/p\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaesi, (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemarnejadian,2015(33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART- na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSanandaj\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGol Mohammadi, 2015(34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGorgan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI and NNRTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaesi, 2014(35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART, ART- na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70\u003c/p\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e62\u003c/p\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJahanbakhsh, 2013(36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eJanuary 2010 to February 2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART- na\u0026iuml;ve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran, Kermanshah and Shiraz\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaesi, 2012(37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART- na\u0026iuml;ve\u003c/p\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaesi,2012(38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI and NNRTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNaziri, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2013\u003c/span\u003e(39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNot reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eART- na\u0026iuml;ve\u003c/p\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eShiraz\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRTI, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHamkar, 2010(40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran\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\u003eNRT, NNRTI, And PI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGholami, 2020(41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran, Khorramabad, Qom, Ahvaz, and Hamedan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNNRTI, NNRT, PI, and INTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMousavi, 2010 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePeople receiving ART\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTehran, Khorramabad, Ahvaz, qom, Hamedan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNRT, NNRTI, PI, and INIs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003ePrevalence Of Acquired Hiv Drug Resistance\u003c/h3\u003e\n\u003cp\u003eThe pooled prevalence of acquired HIVDR among people receiving ART was 34.0% (95% CI: 19.0%-50.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;96.5%) for NRTIs, 27.0% (95% CI: 15.0% -41.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;95.2%) for NNRTIs, and 9.0% (95% CI: 3.0% -18.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;92.6%) for PIs, and zero for INIs. There was a high degree of heterogeneity among studies in all subgroups (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;90%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe pooled prevalence of acquired HIVDR in PLHIV with treatment-failure was 50.0% (95% CI: 31.0% \u0026minus;\u0026thinsp;69.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;89.7%) for NRTIs, 49.0% (95% CI: 29.0%-69.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;90.9%) for NNRTIs, 11.0% (95% CI: 2.0% \u0026minus;\u0026thinsp;24.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;88.1%) for PIs, and 1.0% (95% CI: 0\u0026ndash;4.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0) for INIs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong on treatement PLHIV with resistance to NRTI drugs, the most common mutations were M184V/I (56.4%), T215Y/N/S/F/I (21.3%), and K219E/Q/R (19.0%). Among the patients with resistance to NNRTI drugs, the most common mutations were K103k/N/S/E (52.2%), P225H (16.1%), and Y181C/S (9.2%). Among the patients with resistance to PI drugs, the most common mutations were V82A/I/M/C (29.0%), M46I (27.4%), and L90M (16.1%) (Table\u0026nbsp;\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\u003eFrequency of acquired HIV drug resistance mutations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNRTI Mutations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNNRTI Mutations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ePi Mutations\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (%) of 211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFrequency (%)\u0026thinsp;=\u0026thinsp;184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFrequency (%) N\u0026thinsp;=\u0026thinsp;62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM184V/I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119 (56.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eK103k/N/S/E\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 (52.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eV82A/I/M/C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT215Y/N/S/F/I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (21.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP225H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (16.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eM46I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17 (27.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK219E/Q/R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (19.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM230L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL54V/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (17.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eV75M/C/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (16.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eY181C/S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL90M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (16.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM41L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eV108i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (8.15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL50V/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD67N/G/Q\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eK101Ekqr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eV32i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK70R/T/I/E/Q\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eE138A/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL76v\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT69S/N/P/I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eV179tf\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eI84v\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK65R/E/I/N/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (5.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eK238tn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF77L/C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA98g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL74V/I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eV106mia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eY115F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eH221Y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eL100v\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP236l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN348i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003ePrevalence Of Transmitted Hiv Drug Resistance\u003c/h3\u003e\n\u003cp\u003eThe pooled prevalence of transmitted HIVDR in treatment na\u0026iuml;ve individuals was 3.0% (95% CI; 1.0%-6.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;38.1%) for NRTI, 5.0% (95% CI: 2.0%-9.0%, I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;60.2%) for NNRTI, and 0 for PI and INI. There was a medium degree of heterogeneity among studies in all subgroups (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;54.0%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong teatment-naive PLHIV with resistance to NRTI drugs, the most common mutations were T215Y/N/S/F/I (55.0%), M184V/I (30.0%), and M41L (25.0%). Among the patients with resistance to NNRTI drugs, the most common mutations were K103k/N/S/E (45.7%), E138A/G (28.6%), and V179T/F (25.7%) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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\u003eFrequency of transmitted HIV drug resistance mutation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNRTI related Mutations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNNRTI related Mutations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ePI related Mutations\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (%) of 20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFrequency N\u0026thinsp;=\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFrequency Mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT215Y/N/S/F/I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (55.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eK103knse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eM46I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM184V/I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eE138A/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL76V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eM41L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eV179T/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (25.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eG48V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD67ngq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eV106mia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eL50V/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eY115F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eY181cs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (11.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK65reing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eK101Ekqr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK70rtieq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP225h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eV75M/A/S\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eK238tn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL210W\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK219eqr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this systematic review and meta-analysis, we investigated the pooled prevalence of resistance to NRTI, NNRI, and PI drugs in the treatment na\u0026iuml;ve and people receiving ART. The pooled prevalence of acquired HIVDR in PLHIV was 34.0% for NRTI, 27.0% for NNRTI, and 9.0% for PI. The prevalence of transmitted HIVDR in treatment-naive PLHIV was 3.0% for NRTIs, 5.0% for NNRTIs, and 0% for PIs and INIs.\u003c/p\u003e \u003cp\u003eThe pooled prevalence of acquired HIVDR in PLWH was 34.0% for NRTI, 27.0% for NNRTI, and 9.0% for PI that is higher than the available reports. WHO reported that in 2019, the prevalence of any HIVDR among all individuals receiving treatment ranged from 3.0% in Vietnam to 29.0% in Honduras (8). In our study, the prevalence of HIVDR to NNRTIs among populations for whom NNRTI-based first-line treatment failed was 49.0%; WHO reported that in 2019, the prevalence of NNRTI resistance in these people ranged from 50.0% in Eswatini to 97.0% in Uganda (8). The pooled prevalence of transmitted HIVDR in treatment na\u0026iuml;ve individuals was 3.0% for NRTI, 5.0% for NNRTI. Based on WHO report, pretreatment drug resistance to NNRTI was 7.8% among HIV-infected patients in 18 countries (8).\u003c/p\u003e \u003cp\u003eThere are four possible main reasons for higher prevalence of HIV drug resistance in Iran. First, the frequency of viral load testing in Iran is low. Studies showed that NNRTI-related HIV drug resistance was higher among individuals who monitored viral load less frequently than every three months than more frequently monitored patients (REF). Analysis of national data showed that among 14,685 people on ART in Iran, only 7,471 (50.9%) received viral load testing at least once in 2019 (4). In Iran\u0026rsquo;s national guidline for HIV treatment, viral load testing is recommeded for six months after the initiation of ART for the first time and for every 12 months after. Second, low quality of HIVDR monitoring and surveillance in Iran. WHO reported that quality-of-care indicators associated with the emergence of HIVDR (including retention on ART at 12 months, viral load testing coverage, viral load suppression at 12 months, drug stock-out, and proportion of people on second-line ART) in Iran are not satisfactory (8). Third, low adherence to ART among PLHIV (9). ART adherence in Iran in previous studies ranged from 54.4\u0026ndash;85.0% (10, 11). Fourth, since the self-medication of drugs in Iran is high (67%) (12, 13), drug-drug interaction with other medicines including antibiotics, herbal medicine, or even sedatives can be another reason for the high prevalence of HIV drug resistance (14, 15).\u003c/p\u003e \u003cp\u003eThe most common NRTI resistance mutation was M184V/I, reducing susceptibility to 3TC (lamivudine)/FTC (Emtricitabine). The most common NNRTI resistance mutation was K103k/N/S/E which reduces susceptibility to NVP (nelfinavir) and EFV(efavirenz); the most common PI resistance mutation was M46I and V82A/I/M/C, which reduces susceptibility to IDV (indinavir), NFV (nelfinavir), FPV, ATV (Atazanavir), and LPV (lopinavir)(16). High prevalence of resistance to these drugs can be due to the higher consumption in Iran. The initial drug regimens for PLHIV in Iran before the 2020 was two NRTI (Tenofovir\u0026thinsp;+\u0026thinsp;Emtricitabine OR Tenofovir\u0026thinsp;+\u0026thinsp;Emtricitabine OR Tenofovir\u0026thinsp;+\u0026thinsp;Lamivudine) and one NNRTI (Efavirenz). In the latest treatment guideline in Iran, the initial drug regimen changed to one INI (Dolutegravir) and two NRTI. Information about common HIV drug resistance mutations can be used to adopt a new drug as the preferred first-line treatment.\u003c/p\u003e \u003cp\u003eUnderstanding the reasons for HIVDR is crucial for a better response to this issue. To prevent and respond to HIVDR in Iran, in the latest national guidelines for care and treatment of HIV, the preferred first-line drug for the treatment of HIV changed to Dolutegravir-based antiretroviral regimens (5). This intervention can help prevent HIVDR because Dolutegravir has a high genetic barrier to the resistance (17). Unfortunately, programmatic quality indicators for the HIVDR surveillance in Iran are unsatisfactory (8). Therefore, emphasizing the standardized HIVDR surveys based on WHO guidelines is necessary. Another strategy for monitoring HIVDR is to add routine pretreatment HIVDR testing in the national HIV program to guide regimen selection (3). Studies showed that pretreatment HIVDR testing could improve clinical outcomes. This strategy is currently standard practice in high-income countries (18). A study in Brazil suggests that pretreatment HIVDR testing is a cost-savings task (19), but a study in Kenya showed that it was not cost-effective (20). The cost-effectiveness of new interventions depends on the prevalence of the related problem, availability of resources, and effectiveness thresholds (18). All these suggested the need for cost-effectiveness analysis of pretreatment HIVDR testing in Iran.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eOur study hsd three main limitations. First, there was a high degree of heterogeneity among included studies. By analyzing data in treatment groups (treatment na\u0026iuml;ve, total people receiving ART, and treatment failure people), heterogeneity decreased in treatment na\u0026iuml;ve people, yet it was high in people receiving ART. Second, HIVDR in those who were on treatemet could have been resulted from tranissmission of a drug resistance virus, which we were not able to diffrentiate. Third, included studies have not reported the prevalence of drug resistance by key populations at high risk for HIV (e.g., female sex worker, people who inject drugs, male sex with male).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBased on the results of this systematic review prevalence of HIVDR in Iranian treatment na\u0026iuml;ve and people receiving ART was relatively high. Without universal pretreatment HIVDR testing and more frequent routine viral load testing among PLHIV on ART, these numbers may go up., Providing Dolutegravir based drugs may prevent from transmission of HIVDR mutations. All of these interevetions should also monitoried by a high quality monitoring and surveillnce syatem.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHIVDR: HIV drug resistance\u003c/p\u003e\n\u003cp\u003eART: antiretroviral therapy\u003c/p\u003e\n\u003cp\u003ePLHIV: people living with HIV\u003c/p\u003e\n\u003cp\u003eCI: confidence interval\u003c/p\u003e\n\u003cp\u003eNRTI: nucleoside/nucleotide reverse transcriptase inhibitors\u003c/p\u003e\n\u003cp\u003eNNRTI: non-nucleoside reverse transcriptase inhibitors\u003c/p\u003e\n\u003cp\u003ePI: protease inhibitors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eINI: integrase inhibitors\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eAll authors met the criteria for authorship as established by the International Committee of Medical Journal Editors. Contributions were as follows: HM: Keywords extraction, design search strategy, literature search, literature review, analysis of data, drafting, and critical revisions of the manuscript. SE: design search strategy, literature search, literature review, analysis of data, critical revisions of the manuscript. FM: Keywords extraction, design search strategy, literature review, data abstraction, critical revisions of the manuscript. MRSH: Keywords extraction, literature review, data abstraction, critical revisions of the manuscript. AM: Keywords extraction, design search strategy, literature search, Analysis of data, critical revisions of the manuscript. HSH: Keywords extraction, design search strategy, literature search, literature review, Analysis of data drafting, and critical revisions of the manuscript. MKH: literature review, data abstraction, \u0026nbsp;critical revisions of the manuscript. NN: literature search, literature review, data abstraction, critical revisions of the manuscript\u003c/p\u003e\n\u003cp\u003eConflicts of interest\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;There are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThis article is part of a Ph.D. thesis supported by the Kerman University of Medical Sciences (Grant number: 99000587).\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by Kerman University of Medical Sciences\u003c/p\u003e\n\u003cp\u003eAvailability of data materials\u003c/p\u003e\n\u003cp\u003eAll data generated and analyzed during this study are included in this review.\u003c/p\u003e\n\u003cp\u003eEthical approval and consent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publications\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUNAIDS. 2020 Global AIDS Update ⁠\u0026mdash; Seizing the moment ⁠\u0026mdash; Tackling entrenched inequalities to end epidemics. 2020. avalable at: https://www.unaids.org/en/resources/documents/2020/global-aids-report.\u003c/li\u003e\n\u003cli\u003eGuidelines on the public health response to pretreatment HIV drug resistance, July 2017. 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J Med Virol. 2014;86(7):1093-8.10.1002/jmv.23898\u003c/li\u003e\n\u003cli\u003eJahanbakhsh F, Hattori J, Matsuda M, Ibe S, Monavari SH, Memarnejadian A, et al. Prevalence of transmitted HIV drug resistance in Iran between 2010 and 2011. PLoS One. 2013;8(4):e61864.10.1371/journal.pone.0061864\u003c/li\u003e\n\u003cli\u003eBaesi K, Ravanshad M, Ghanbari Safari M, Saberfar E, Hajiabdolbaghi M. Drug Resistance of HIV-1 protease gene among AIDS patients in Iranian research center for AIDS. Pathobiology Reaearch. 2012;14(4):14\u003c/li\u003e\n\u003cli\u003eBaesi K, Ravanshad M, Hosseini Y, Abdolbaghi MH. Drug resistance profile and subtyping of HIV-1 RT gene in Iranian patients under treatment. Iran J Biotechnol. 2012;10(1):1-7\u003c/li\u003e\n\u003cli\u003eNaziri h, Tabarraei a, Ghaemi a, Davarpanah m, Javid a, Moradi a. Drug-resistance-associated mutations and hiv sub-type determination in drug-naive and hiv-positive patients under treatment with antiretroviral drugs. Med Lab J. 2013;7(3):-\u003c/li\u003e\n\u003cli\u003eHamkar R, Mohraz M, Lorestani S, Aghakhani A, Truong H-HM, McFarland W, et al. Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. AIDS. 2010;24:S85-S91.10.1097/01.aids.0000386738.32919.67\u003c/li\u003e\n\u003cli\u003eGholami M, Rouzbahani N, Samiee S, Tayeri K, Ghorban K, Dehkharghani AD, et al. HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform. Microb Pathog. 2020;146:8.10.1016/j.micpath.2020.104221\u003c/li\u003e\n\u003cli\u003eMousavi SM, Hamkar R, Gouya MM, Safaie A, Zahraei SM, Yazdani Z, et al. Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study. Arch Virol. 2010;155(3):329-34.10.1007/s00705-009-0583-6\u003c/li\u003e\n\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":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anti-Retroviral Agents, Drug Resistance, Drug Resistance, Viral, HIV Infections, Treatment Failure ","lastPublishedDoi":"10.21203/rs.3.rs-2766057/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2766057/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere are no national-level surveys about HIV drug resistance (HIVDR) in Iran. Therefore, this investigation aimed to estimate the prevalence of HIVDR among antiretroviral therapy (ART) na\u0026iuml;ve people (those without a history of ART) and people receiving ART.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethod\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe systematically searched Scopus, PubMed, Web of Science, Embase, Iranian database, the references of studies, and google scholar till March, 2023. A random-effect model was implemented to calculate point estimate and 95% confidence interval (95% CI) for the prevalence of HIVDR in people living with HIV (PLHIV).\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong 461 potential publications, 22 studies were included in the meta-analysis. The pooled prevalence of acquired HIVDR in people receiving ART was 34.0% (95% CI: 19.0%-50.0%) for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 27.0% (95% CI: 15.0% -41.0%) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 9.0% (95% CI: 3.0% -18.0%) for protease inhibitors (PIs). The pooled prevalence of Acquired HIVDR in treatment failure PLHIV was 50.0% (95% CI: 31.0% \u0026minus;\u0026thinsp;69.0%) for NRTI, 49.0% (95% CI: 29.0%-69.0%) for NNRTI, 11.0% (95% CI: 2.0% \u0026minus;\u0026thinsp;24.0%) for PI, and 1.0% (95% CI: 0\u0026ndash;4.0%) for integrase inhibitors (INIs). The pooled prevalence of transmitted HIVDR in treatment na\u0026iuml;ve people was 3.0% (95% CI; 1.0%-6.0%) for NRTI, 5.0% (95% CI: 2.0%-9.0%) for NNRTI, and 0 for PIs and INIs.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe prevalence of HIVDR in Iranian treatment na\u0026iuml;ve and people receiving ART was relatively high. Without universal pretreatment HIVDR testing and more frequent routine viral load testing among PLHIV who are on ART, these numbers may go up.\u003c/p\u003e","manuscriptTitle":"Prevalence of acquired and transmitted HIV drug resistance in Iran: A systematic review and Metaanalysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-11 14:50:25","doi":"10.21203/rs.3.rs-2766057/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-09-15T12:08:14+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-09-01T08:45:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"427caf26-d126-4353-994b-de4fc7671dfc","date":"2023-08-24T12:56:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-08-24T10:45:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-24T08:01:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-04-09T08:52:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-04-09T08:46:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2023-04-01T20:22:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"624923cf-b55d-470a-bf6f-d5fdd1a2bdb0","owner":[],"postedDate":"April 11th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-01-08T15:06:12+00:00","versionOfRecord":{"articleIdentity":"rs-2766057","link":"https://doi.org/10.1186/s12879-023-08916-3","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2024-01-02 15:00:48","publishedOnDateReadable":"January 2nd, 2024"},"versionCreatedAt":"2023-04-11 14:50:25","video":"","vorDoi":"10.1186/s12879-023-08916-3","vorDoiUrl":"https://doi.org/10.1186/s12879-023-08916-3","workflowStages":[]},"version":"v1","identity":"rs-2766057","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2766057","identity":"rs-2766057","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}