Brief Communication: Impact of Pretreatment HIV-1 Drug Resistance on Virologic Outcomes in Ugandan Patients infected with Non-B HIV-1 Subtypes

Brief Communication: Impact of Pretreatment HIV-1 Drug Resistance on Virologic Outcomes in Ugandan Patients infected with Non-B HIV-1 Subtypes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Brief Communication: Impact of Pretreatment HIV-1 Drug Resistance on Virologic Outcomes in Ugandan Patients infected with Non-B HIV-1 Subtypes Fred Kyeyune, Eva Nabulime, Pamela Ainembabazi, Tamale William, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9308576/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Background Pretreatment HIV-1 drug resistance (PDR), including minority variants, may compromise antiretroviral therapy (ART) outcomes but remains underexplored in non-B HIV-1 subtypes. Methods This longitudinal study enrolled 106 ART-naïve Ugandan adults (2018–2020) to assess the impact of majority (≥ 20%) and minority (< 20%) pretreatment HIV-1 drug resistance mutations on virologic outcomes using next-generation sequencing of baseline HIV-1 RNA. Viral load was measured at 6, 12, and 24 months, and associations between PDR and cumulative viral load were evaluated among 38 participants with complete follow-up. Results Majority HIVDRMs were most frequent in NNRTIs and NRTIs, while minority variants were more common in PIs and INSTIs. Among participants with complete follow-up, 26% had detectable cumulative VL, of whom 91% harbored at least one HIVDRM. PDR was not significantly associated with detectable VL (OR = 5.29, 95% CI: 0.58–48.20; p = 0.224), although a trend toward poorer virologic outcomes was observed. Conclusion Pretreatment HIVDRMs, may adversely affect virologic outcomes, although no statistically significant association was observed. Expanding access to baseline resistance testing could improve ART selection and treatment outcomes in settings with diverse HIV-1 subtypes. pretreatment HIV drug resistance minority variants next-generation sequencing Figures Figure 1 Introduction Antiretroviral therapy (ART) has markedly improved outcomes for people living with HIV (PLWH), but HIV drug resistance (HIVDR) remains a major challenge and contributes to treatment failure ( 1 , 2 ). Pretreatment HIV drug resistance (PDR) occurs when individuals initiate ART with pre-existing resistance mutations, either through transmission of resistant strains or prior exposure to suboptimal therapy ( 3 ). In resource-limited settings, where resistance testing is not routinely performed, PDR may compromise treatment outcomes ( 4 , 5 ). HIV drug-resistant variants emerge before treatment failure, making routine viral load monitoring critical ( 5 , 6 ). In resource-limited settings, poor adherence due to structural barriers drives resistance development ( 5 ) necessitating timely, informed regimen switches to maintain viral suppression ( 7 ). Standard HIV-1 drug resistance testing relies on population-based Sanger sequencing, which detects majority HIV drug resistance mutations (HIVDRMs; ≥20% of the viral population) ( 6 , 8 ). Minority variants (< 20%) are typically undetectable but can be identified using next-generation sequencing (NGS) ( 6 , 9 ). Although PDR has been associated with poorer ART outcomes ( 10 ), the impact of minority variants remains underexplored, particularly in non-B HIV-1 subtypes. We therefore used NGS to characterize pretreatment HIVDRMs and evaluate their association with virologic outcomes over 24 months following ART initiation. Methods Newly diagnosed HIV-1-positive adults (≥ 18 years) were recruited prior to ART initiation from Joint Clinical Research Centre (JCRC) and Kampala Capital City Authority clinics between 2018 and 2020. Participants were followed longitudinally at baseline, and at 6, 12, and 24 months post-ART initiation. Samples for HIV-1 drug resistance testing were analyzed at the Centers for Aids Research (CFAR) Molecular Biology Laboratory at JCRC, Baseline plasma samples were processed for RNA extraction and HIV-1 genotypic drug resistance testing. The HIV-1 pol gene (protease to integrase) was amplified by PCR and sequenced using next-generation sequencing (Illumina MiSeq). Sequence analysis was performed using HYDRA with mutation interpretation based on the Stanford HIV Drug Resistance Database ( 11 , 12 ). Viral load (VL) testing was conducted at baseline and follow-up using standard clinical platforms (20–1.0 × 10⁷ cp/ml range). HIV-1 subtypes were assigned using REGA version 3 ( 13 ). Associations between pretreatment drug resistance and virologic outcomes were assessed using Fisher’s exact test. Results Socio-demographic characteristics of study participants A total of 106 participants (57% female) were enrolled, and HIV-1 RNA was successfully sequenced for all. The cohort predominantly comprised urban and peri-urban residents of low socioeconomic status and was presumed ART-naïve at enrollment. Participants with prior exposure to ART, chemotherapy, or radiation were excluded. Participants were initiated on tenofovir/lamivudine/dolutegravir (TLD; n = 40, 82.5% male) or tenofovir/lamivudine/efavirenz (TLE; n = 53, 14% male), while 13 did not initiate ART. The predominance of males in the TLD group reflects earlier caution in prescribing dolutegravir to women of reproductive age ( 14 ). Participants were followed for 24 months; 38 completed follow-up with VL data at all time points. All infections were due to non-B HIV-1 subtypes, predominantly subtype A, D, and recombinant forms. The study was not powered to assess subtype-specific differences in outcomes. Pretreatment HIVDR patterns We analyzed the prevalence of individual HIVDRMs and resistance across ARV drug classes (Supplementary Fig. S1 a-b). Majority HIVDRMs were most frequent in NNRTIs and NRTIs, whereas INSTIs exhibited the highest prevalence of minority variants. No majority HIVDRMs were observed in INSTIs (Supplementary Fig. S1 a). Intraclass analysis showed variable resistance across drug classes: majority HIVDRMs were highest in NNRTIs (14.2%), while INSTIs had the highest proportion of minority variants (12.5%, Supplementary Fig. S1 b). These findings are consistent with the widespread use of NNRTI- and NRTI-based first-line regimens ( 14 ). For the majority DRM, the general trend was that the commonly used inhibitors displayed more ARV drug resistance than those that were rarely used. We observed a greater frequency of majority HIVDRM in the NNRTI drug class than in the NRTI and no majority HIVDRM to INST. Surprisingly, there was substantial minority HIVDRM in all drug classes. Impact of pretreatment resistance on treatment outcome Impact of pretreatment resistance on treatment outcome The Uganda National ART Guidelines recommends VL testing at 6 and 12 months after ART initiation and annually thereafter ( 15 ). In accordance with these guidelines, study participants were followed for 24 months, with VL testing performed at 6, 12, and 24 months post-ART initiation. Only participants who completed the 24-month follow-up and had VL results available at all three time points were included in this analysis (Table 1 ). A total of 38 participants met these criteria. Loss to follow-up was primarily attributable to the historical nationwide lockdowns implemented in 2020 and 2021 to control the spread of SARS-CoV-2 infection. These restrictions disrupted clinical services and access to treatment. As a result, some participants relocated to other clinics, while others were lost to follow-up for unknown reasons. Table 1 Baseline HIV Drug Resistance Mutations and Longitudinal Virologic Monitoring Over 24 Months Post-ART Initiation. Participant ID VL at 6 months (cp/mL) VL at 12 months (cp/mL) VL at 24 months (cp/mL) Cumulative VL (cp/mL) Log10 Cumulative VL TRM TDR27 0 0 30 30 1.5 0 TDR28 0 0 56 56 1.7 0 TDR30 0 50 1 51 1.7 1 TDR61 0 0 1 1 0.0 0 TDR62 0 0 1 1 0.0 0 TDR73 106 0 1 107 2.0 0 TDR79 1610 50 2300 3960 3.6 1 TDR89 0 74 1 75 1.9 0 TDR90 0 74 0 74 1.9 2 TDR91 0 0 1 1 0.0 0 TDR102 0 0 1 1 0.0 0 TDR105 0 0 1 1 0.0 0 TDR111 0 0 1 1 0.0 0 TDR114 0 1 1 2 0.3 0 TDR115 839 50 1 890 2.9 0 TDR120 64 0 146 210 2.3 0 TDR126 0 1 149 150 2.2 0 TDR130 0 50 54 104 2.0 1 TDR131 251 0 40 291 2.5 0 TDR132 0 0 30 30 1.5 0 TDR133 0 0 1 1 0.0 0 TDR135 253 63 30 346 2.5 0 TDR139 584 108 1 693 2.8 1 TDR151 0 0 50 50 1.7 0 TDR153 0 115000 1 115001 5.1 0 TDR155 0 0 790 790 2.9 0 TDR156 0 0 1 1 0.0 0 TDR158 0 50 1 51 1.7 0 TDR160 591 0 1 592 2.8 1 TDR161 0 0 1 1 0.0 1 TDR162 0 50 1 51 1.7 0 TDR165 272 0 50 322 2.5 1 TDR166 0 0 1310 1310 3.1 0 TDR178 0 50 50 100 2.0 1 TDR180 4270000 53 30 4270083 6.6 0 TDR182 340 0 1 341 2.5 1 TDR188 88 839 9410 10337 4.0 4 VL, viral load; TRM, total resistance mutations. Viral load is expressed in copies per milliliter (cp/mL) and was measured at 6, 12, and 24 months following antiretroviral therapy (ART) initiation. The table includes participants who completed 24-month follow-up (n = 38). Baseline HIV drug resistance mutations (HIVDRMs) were determined prior to ART initiation using next-generation sequencing and are summarized as TRM, including both majority (≥ 20%) and minority (< 20%) variants. Cumulative VL represents the sum of VL measurements across all time points, and log10 cumulative VL indicates its logarithmic transformation. Due to the small number of participants who completed the 24-month follow-up, there was no separate analysis for either majority or minority HIVDRM patients (Table 1 ). The log-transformed cumulative viral load (VL) values presented in Table 1 were paired with the corresponding total number of HIV drug resistance mutations (TRMs) and analyzed using Fisher’s exact test (Table 1 , and Fig. 1 ). Participants were categorized as having detectable or undetectable cumulative viral load for this analysis. The presence of HIVDRMs was not significantly associated with detectable cumulative viral load. Although the estimated odds ratio suggested a potentially strong association (OR = 5.29), the relationship was not statistically significant (95% CI: 0.58–48.20; p = 0.224), likely reflecting limited statistical power due to the small sample size (n = 38) (Table 1 , Fig. 1 a). Notably, 91% of participants harboring at least one HIV drug resistance mutation (HIVDRM) had a detectable viral load during follow-up (Fig. 1 a). These individuals represented approximately 26% of the total participants who completed the study. Importantly, all participants within this subgroup exhibited both a detectable viral load and at least one HIVDRM (VL+/DR+) (Fig. 1 b). Discussion Non-B HIV-1 subtypes, predominant in sub-Saharan Africa, are understudied despite their global burden. PDR contributes to suboptimal virologic outcomes, and while most studies focus on majority variants ( 16 ), our findings demonstrate that both majority and minority HIVDRMs may influence treatment outcomes. This study, conducted in a non-B subtype-dominant setting, highlights the added clinical value of detecting minority variants. Most participants (91%) with pretreatment HIVDRMs had detectable viral load over 24 months (Fig. 1 a), demonstrating a strong link between baseline resistance and poor virologic control. Notably, minority variants, undetectable by standard assays, also appeared to influence viral replication and treatment failure, underscoring the need to detect both variant types when evaluating ART effectiveness. Prolonged use of NRTI- and NNRTI-based regimens has contributed to widespread HIVDRMs within these drug classes ( 17 ). In our cohort, common mutations included NRTI-associated M184VI, K65R, and K219QE, and NNRTI-associated K103NS and G190ASE (Supplementary Fig. S1 a), which confer resistance to the widely used agents such as 3TC, AZT, TDF, and EFV. These mutations were observed in both majority and minority variants, suggesting selective pressure from extensive drug exposure and transmission of resistant strains ( 5 ). In contrast, PIs and INSTIs showed low levels of majority HIVDRMs but relatively higher levels of minority variants, likely reflecting their more limited use in first-line therapy. ( 17 ). HIVDRMs present at ART initiation can support ongoing viral replication, resulting in low-level viremia or viral blips, known predictors of future virologic failure ( 5 ). In this study, individuals with pretreatment HIVDRMs were more likely to experience virologic failure compared to those without resistance (OR = 5.29), although this association did not reach statistical significance (p = 0.224). The high rate of virologic failure among participants with baseline resistance (91%, Fig. 1 a) suggests a biologically meaningful trend that may have been underpowered due to sample size constraints. While the clinical significance of minority variants remains an area of ongoing investigation, our findings suggest they may contribute to suboptimal virologic outcomes. These findings support the utility of baseline resistance testing to guide individualized ART selection, particularly in settings where archived mutations may re-emerge under drug pressure ( 3 ). Study limitations A substantial proportion of participants did not complete the 24-month follow-up, primarily due to SARS-CoV-2–related movement restrictions, resulting in a reduced sample size and limited statistical power. Additionally, the study was conducted in a central region with relatively better access to healthcare services, which may limit generalizability to populations in more remote settings. Conclusion Pretreatment HIVDRMs, including minority variants, may adversely affect virologic outcomes, although no statistically significant association was observed in this study. These findings highlight the importance of ongoing surveillance of pretreatment drug resistance. Where feasible, baseline resistance testing could improve ART selection and help mitigate the risk of treatment failure Abbreviations 3TC: lamivudine AIDS: Acquired immunodeficiency syndrome ART: antiretroviral therapy ARV: antiretroviral AZT: Zidovudine CFAR: Center for AIDS research Cp/ml : copies per milliliter DNA: deoxyribonucleic acid EFV: Efavirenz HIV: Human immunodeficiency virus HIVDR: HIV drug resistance HIVDRMs: HIV-1 drug resistance mutations INSTIs: integrase strand transfer inhibitors JCRC: Joint Clinical Research Centre KCCA: Kampala City Council Authority NGS: next-generation sequencing NNRTIs: nonnucleoside reverse transcriptase inhibitors NRTIs: nucleoside reverse transcriptase inhibitors NVP: Nevirapine PCR: Polymerase chain reaction PDR: Pretreatment HIV-1 drug resistance PIs: protease inhibitors PLWH: people living with HIV-1 RNA: ribonucleic acid TDF:tenofovir TLD: tenofovir/lamuvidine/doultegravir TLE: tenofovir/lamuvidine/Efavirenz uL: microliter VL: viral load WHO: World Health Organization Declarations Ethical approval The study was conducted in accordance with the principles of the Declaration of Helsinki. The study was approved by the Research and Ethics Committee (REC) at JCRC and the Uganda National Council for Science and Technology. Consent to participate: Written informed consent was obtained from all participants prior to enrollment in the study. Consent for publication Not applicable Availability of data and materials The dataset(s) supporting the conclusions of this article is(are) available in the GenBank repository under the accession number PP995671 - PP995775 Funding statement This study was supported by the Case Western Reserve University/University Hospitals Center for AIDS Research developmental grant (A1036219:RES508058). Authors and Affiliations Center for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda Fred Kyeyune, Eva Nabulime, Pamela Ainembabazi , William Tamale , Joel Kabali , Alisen Ayitewala , Immaculate Nankya Corresponding author: Fred Kyeyune, Center For AIDS Research, Case Western Reserve University Cleveland Ohio and Joint Clinical Research Centre Uganda Tel:+256786224191 ( [email protected] ) Author contributions F.K. and I.N. designed and oversaw the implementation of the study, data analysis and manuscript writing; T.W. was the study doctor and enrolled the patients; P.A., J.K., E.N., A.A., F.K. and I.N. performed the laboratory experiments and data collection. Acknowledgment The authors acknowledge the people living with HIV-1 who participated in this study, staff from the Kampala City Council Authority and Joint Clinical Research Centre clinics’ outpatient departments, and advisors from both Joint Clinical Research and the Center for AIDS Research, Case Western Reserve University. Competing interests The authors declare they have no competing interests References Weiser B,SB,KK,BH,MH,SQ,GW,RE,HS,ST,GA,AK,&RC. Long-term antiretroviral therapy mitigates mortality and morbidity independent of HIV tropism: 18 years follow-up in a women's cohort. AIDS (London, England). 2022; 36(14): p. 1979–1986. Zhang T,LL,SY,FY,RY,&XH. Relationship Between Drug Resistance and Death in HIV-Infected Patients Receiving Antiretroviral Therapy - 7 PLADs, China, 2010-2019. 2021; 3(14): p. 291–297. Macdonald V,ML,JMR,MB,JS,BR,VA,&BS. Prevalence of pretreatment HIV drug resistance in key populations: a systematic review and meta-analysis. Journal of the International AIDS Society. 2020; 23(12): p. e25656. Shafer RW,&VDA. Highly active antiretroviral therapy (HAART) for the treatment of infection with human immunodeficiency virus type 1. Biomedicine & pharmacotherapy. 1999; 53(2): p. 73–86. Bello KJ,MO,OTA,WSH,LT,GA,ABK,&OJF. Factors associated with 10 years of continuous viral load suppression on HAART. BMC infectious diseases. 2016; 16: p. 351. Kyeyune F,GRM,NI,VC,MS,AJ,NE,KCM,SRA,MP,AEJ,&QMME. Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure. Antimicrobial agents and chemotherapy. 2016; 60(6): p. 3380–3397. Van Vaerenbergh K. Study of the impact of HIV genotypic drug resistance testing on therapy efficacy. Verh K Acad Geneeskd Belg. 2001; 63(5): p. 447-73. Balakrishna S,LT,ZM,FP,HM,KK,YS,LK,PM,RA,WC,FC,KP,GA,HHH,SM,RA,CM,BE,N. Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1. The Journal of antimicrobial chemotherapy. 2023; 78(3): p. 656–664. Mohamed S,BR,&SC. From Capillary Electrophoresis to Deep Sequencing: An Improved HIV-1 Drug Resistance Assessment Solution Using In Vitro Diagnostic (IVD) Assays and Software. Viruses. 2023; 15(2): p. 571. Hermans LE,HLM,SR,THR,BDM,TSAJ,DJD,THA,VWDF,NM,&WAMJ. HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment. AIDS (London, England). 2022; 36(7): p. 923–931. Taylor T,LER,NM,EE,LB,CR,GMK,DGV,SP,BJ,&JH. A MiSeq-HyDRA platform for enhanced HIV drug resistance genotyping and surveillance. Scientific reports. 2019; 9(1): p. 8970. W. SR. Rationale and uses of a public HIV drug-resistance database. The Journal of infectious diseases. 2006; 194(S51–S58): p. S51–S58. Pineda-Peña AC,FNR,IS,LP,AAB,DK,GLA,CRJ,dOT,&VAM. Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools.. journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2013; 19: p. 337-348. WHO. WHO releases HIV drug resistance report 2021. Geneva:; 2021. Organization WH. CONSOLIDATED GUIDELINES FOR THE PREVENTION AND TREATMENT OF HIV AND AIDS.; 2021. Available from: https://elearning.idi.co.ug/wp-content/uploads/2022/05/Consolidated-Guidelines-for-the-Prevention-and-Treatment-of-HIV-and-AIDS-in-Uganda-2020.pdf. Boender TS,HBM,SKC,HRL,WM,ST,SM,LMEE,NI,KCM,ATA,AAS,MK,BME,OP,&RdWTF. Pretreatment HIV drug resistance increases regimen switches in sub-Saharan Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015; 61(11): p. 1749–1758. Ayitewala A KFAPNEKCNI. Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. AIDS Res Therapy. 2020; 17(1): p. 2. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFile1.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 08 May, 2026 Reviews received at journal 24 Apr, 2026 Reviews received at journal 21 Apr, 2026 Reviewers agreed at journal 10 Apr, 2026 Reviewers agreed at journal 10 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviewers invited by journal 08 Apr, 2026 Editor invited by journal 08 Apr, 2026 Editor assigned by journal 08 Apr, 2026 Submission checks completed at journal 08 Apr, 2026 First submitted to journal 02 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9308576","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621165363,"identity":"0759813d-4dbc-4f33-b411-7dff98cd6681","order_by":0,"name":"Fred Kyeyune","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBAC9h4og5/hAJFaeM5AGZINJGsxIFYHAw/PGcPHvG135IwPHn724QeDTb68A4/xC7xaeHuMjXnbnhmbHThmPLOHIc1y4wEeMwt8Wuz5ecykedsOJ247cIaZmYHhsIFhA4+ZAV5b+HnMfwO11G9uIFoLb48ZM1BLggEDVIs8A4/xA7xaeI4VS845d9hwBtAvjD0GaQYGzGxl+HQAtSRv/PCm7LA8/4zDjxl+VNgYyLc3b/6AVw8DhwETD4iWOAAkgJ4wOMzAJoFfC/sDxh8gmr8BwpdvYGAmYMsoGAWjYBSMMAAAKgVFjNF/zwYAAAAASUVORK5CYII=","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":true,"prefix":"","firstName":"Fred","middleName":"","lastName":"Kyeyune","suffix":""},{"id":621165365,"identity":"d0a7ebaf-afd4-4a77-8d01-79fcb491c0ba","order_by":1,"name":"Eva Nabulime","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Nabulime","suffix":""},{"id":621165366,"identity":"63bd44f0-2455-47fc-b400-26c0310d42c4","order_by":2,"name":"Pamela Ainembabazi","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Pamela","middleName":"","lastName":"Ainembabazi","suffix":""},{"id":621165367,"identity":"220c8782-f564-4a2d-a972-62b1f6bebcb1","order_by":3,"name":"Tamale William","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Tamale","middleName":"","lastName":"William","suffix":""},{"id":621165368,"identity":"d2a6e2fb-2c07-4cab-bd2a-49d05df250e9","order_by":4,"name":"Joel Kabali","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Joel","middleName":"","lastName":"Kabali","suffix":""},{"id":621165370,"identity":"6a2cecd9-638f-42db-8d43-c79404cf7f40","order_by":5,"name":"Alisen Ayitewala","email":"","orcid":"","institution":"Central Public Health Laboratories","correspondingAuthor":false,"prefix":"","firstName":"Alisen","middleName":"","lastName":"Ayitewala","suffix":""},{"id":621165372,"identity":"ef53425b-01cd-451f-962a-c74c42f7392f","order_by":6,"name":"Immaculate Nankya","email":"","orcid":"","institution":"Joint Clinical Research Centre","correspondingAuthor":false,"prefix":"","firstName":"Immaculate","middleName":"","lastName":"Nankya","suffix":""}],"badges":[],"createdAt":"2026-04-03 04:08:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9308576/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9308576/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107246278,"identity":"6cf88639-8f58-4934-912f-f05f40d08be8","added_by":"auto","created_at":"2026-04-19 08:10:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21407,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVirologic outcomes during 24 months of antiretroviral therapy (ART).\u003cbr\u003e\n(\u003c/strong\u003ea) Proportion of individuals with detectable and undetectable viral load (VL), stratified by pretreatment genotype (wild-type [WT] vs mutant [≥1 HIV drug resistance mutation, HIVDRM]). For each genotype group, total (100%), detectable VL, and undetectable VL are shown.\u003c/p\u003e\n\u003cp\u003e(b) Distribution of HIVDRM status and VL outcomes, categorized as no HIVDRM with detectable VL (0DR+VL), ≥1 HIVDRM with detectable VL (1DR+VL), ≥1 HIVDRM with undetectable VL (1DR+NoVL), and no HIVDRM with undetectable VL (0DR+NoVL). Percentages are based on participants who completed the 24-month follow-up.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9308576/v1/4ace3846b9835801b2a054b2.png"},{"id":107246401,"identity":"c6df4fbd-e98e-4129-a29a-926b0ebdb69d","added_by":"auto","created_at":"2026-04-19 08:10:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":464001,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9308576/v1/14a73f47-1aec-4e32-86ca-75d25d30b36e.pdf"},{"id":107246267,"identity":"b321fe58-9c50-4874-92fa-2a189c5b43c0","added_by":"auto","created_at":"2026-04-19 08:10:05","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":204347,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9308576/v1/1137d8dc5d758048c64251b4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Brief Communication: Impact of Pretreatment HIV-1 Drug Resistance on Virologic Outcomes in Ugandan Patients infected with Non-B HIV-1 Subtypes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAntiretroviral therapy (ART) has markedly improved outcomes for people living with HIV (PLWH), but HIV drug resistance (HIVDR) remains a major challenge and contributes to treatment failure (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePretreatment HIV drug resistance (PDR) occurs when individuals initiate ART with pre-existing resistance mutations, either through transmission of resistant strains or prior exposure to suboptimal therapy (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In resource-limited settings, where resistance testing is not routinely performed, PDR may compromise treatment outcomes (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHIV drug-resistant variants emerge before treatment failure, making routine viral load monitoring critical (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In resource-limited settings, poor adherence due to structural barriers drives resistance development (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) necessitating timely, informed regimen switches to maintain viral suppression (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStandard HIV-1 drug resistance testing relies on population-based Sanger sequencing, which detects majority HIV drug resistance mutations (HIVDRMs; \u0026ge;20% of the viral population) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Minority variants (\u0026lt;\u0026thinsp;20%) are typically undetectable but can be identified using next-generation sequencing (NGS) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Although PDR has been associated with poorer ART outcomes (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), the impact of minority variants remains underexplored, particularly in non-B HIV-1 subtypes. We therefore used NGS to characterize pretreatment HIVDRMs and evaluate their association with virologic outcomes over 24 months following ART initiation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eNewly diagnosed HIV-1-positive adults (\u0026ge;\u0026thinsp;18 years) were recruited prior to ART initiation from Joint Clinical Research Centre (JCRC) and Kampala Capital City Authority clinics between 2018 and 2020. Participants were followed longitudinally at baseline, and at 6, 12, and 24 months post-ART initiation. Samples for HIV-1 drug resistance testing were analyzed at the Centers for Aids Research (CFAR) Molecular Biology Laboratory at JCRC,\u003c/p\u003e \u003cp\u003eBaseline plasma samples were processed for RNA extraction and HIV-1 genotypic drug resistance testing. The HIV-1 \u003cem\u003epol\u003c/em\u003e gene (protease to integrase) was amplified by PCR and sequenced using next-generation sequencing (Illumina MiSeq). Sequence analysis was performed using HYDRA with mutation interpretation based on the Stanford HIV Drug Resistance Database (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Viral load (VL) testing was conducted at baseline and follow-up using standard clinical platforms (20\u0026ndash;1.0 \u0026times; 10⁷ cp/ml range). HIV-1 subtypes were assigned using REGA version 3 (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Associations between pretreatment drug resistance and virologic outcomes were assessed using Fisher\u0026rsquo;s exact test.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSocio-demographic characteristics of study participants\u003c/h2\u003e \u003cp\u003e A total of 106 participants (57% female) were enrolled, and HIV-1 RNA was successfully sequenced for all. The cohort predominantly comprised urban and peri-urban residents of low socioeconomic status and was presumed ART-na\u0026iuml;ve at enrollment. Participants with prior exposure to ART, chemotherapy, or radiation were excluded.\u003c/p\u003e \u003cp\u003eParticipants were initiated on tenofovir/lamivudine/dolutegravir (TLD; n\u0026thinsp;=\u0026thinsp;40, 82.5% male) or tenofovir/lamivudine/efavirenz (TLE; n\u0026thinsp;=\u0026thinsp;53, 14% male), while 13 did not initiate ART. The predominance of males in the TLD group reflects earlier caution in prescribing dolutegravir to women of reproductive age (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Participants were followed for 24 months; 38 completed follow-up with VL data at all time points.\u003c/p\u003e \u003cp\u003eAll infections were due to non-B HIV-1 subtypes, predominantly subtype A, D, and recombinant forms. The study was not powered to assess subtype-specific differences in outcomes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePretreatment HIVDR patterns\u003c/h3\u003e\n\u003cp\u003eWe analyzed the prevalence of individual HIVDRMs and resistance across ARV drug classes (Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea-b). Majority HIVDRMs were most frequent in NNRTIs and NRTIs, whereas INSTIs exhibited the highest prevalence of minority variants. No majority HIVDRMs were observed in INSTIs (Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea). Intraclass analysis showed variable resistance across drug classes: majority HIVDRMs were highest in NNRTIs (14.2%), while INSTIs had the highest proportion of minority variants (12.5%, Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eb). These findings are consistent with the widespread use of NNRTI- and NRTI-based first-line regimens (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). For the majority DRM, the general trend was that the commonly used inhibitors displayed more ARV drug resistance than those that were rarely used. We observed a greater frequency of majority HIVDRM in the NNRTI drug class than in the NRTI and no majority HIVDRM to INST. Surprisingly, there was substantial minority HIVDRM in all drug classes.\u003c/p\u003e\n\u003ch3\u003eImpact of pretreatment resistance on treatment outcome\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eImpact of pretreatment resistance on treatment outcome\u003c/div\u003e \u003cp\u003eThe Uganda National ART Guidelines recommends VL testing at 6 and 12 months after ART initiation and annually thereafter (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In accordance with these guidelines, study participants were followed for 24 months, with VL testing performed at 6, 12, and 24 months post-ART initiation. Only participants who completed the 24-month follow-up and had VL results available at all three time points were included in this analysis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A total of 38 participants met these criteria.\u003c/p\u003e \u003cp\u003eLoss to follow-up was primarily attributable to the historical nationwide lockdowns implemented in 2020 and 2021 to control the spread of SARS-CoV-2 infection. These restrictions disrupted clinical services and access to treatment. As a result, some participants relocated to other clinics, while others were lost to follow-up for unknown reasons.\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\u003eBaseline HIV Drug Resistance Mutations and Longitudinal Virologic Monitoring Over 24 Months Post-ART Initiation.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParticipant ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVL at 6 months (cp/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVL at 12 months (cp/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVL at 24 months (cp/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCumulative VL (cp/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLog10 Cumulative VL\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTRM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3960\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e584\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e693\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e115000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e115001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e591\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e592\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e322\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4270000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4270083\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e340\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDR188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVL, viral load; TRM, total resistance mutations. Viral load is expressed in copies per milliliter (cp/mL) and was measured at 6, 12, and 24 months following antiretroviral therapy (ART) initiation. The table includes participants who completed 24-month follow-up (n\u0026thinsp;=\u0026thinsp;38). Baseline HIV drug resistance mutations (HIVDRMs) were determined prior to ART initiation using next-generation sequencing and are summarized as TRM, including both majority (\u0026ge;\u0026thinsp;20%) and minority (\u0026lt;\u0026thinsp;20%) variants. Cumulative VL represents the sum of VL measurements across all time points, and log10 cumulative VL indicates its logarithmic transformation.\u003c/p\u003e \u003cp\u003eDue to the small number of participants who completed the 24-month follow-up, there was no separate analysis for either majority or minority HIVDRM patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe log-transformed cumulative viral load (VL) values presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e were paired with the corresponding total number of HIV drug resistance mutations (TRMs) and analyzed using Fisher\u0026rsquo;s exact test (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Participants were categorized as having detectable or undetectable cumulative viral load for this analysis. The presence of HIVDRMs was not significantly associated with detectable cumulative viral load. Although the estimated odds ratio suggested a potentially strong association (OR\u0026thinsp;=\u0026thinsp;5.29), the relationship was not statistically significant (95% CI: 0.58\u0026ndash;48.20; p\u0026thinsp;=\u0026thinsp;0.224), likely reflecting limited statistical power due to the small sample size (n\u0026thinsp;=\u0026thinsp;38) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). Notably, 91% of participants harboring at least one HIV drug resistance mutation (HIVDRM) had a detectable viral load during follow-up (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). These individuals represented approximately 26% of the total participants who completed the study. Importantly, all participants within this subgroup exhibited both a detectable viral load and at least one HIVDRM (VL+/DR+) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eNon-B HIV-1 subtypes, predominant in sub-Saharan Africa, are understudied despite their global burden. PDR contributes to suboptimal virologic outcomes, and while most studies focus on majority variants (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), our findings demonstrate that both majority and minority HIVDRMs may influence treatment outcomes. This study, conducted in a non-B subtype-dominant setting, highlights the added clinical value of detecting minority variants.\u003c/p\u003e \u003cp\u003eMost participants (91%) with pretreatment HIVDRMs had detectable viral load over 24 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea), demonstrating a strong link between baseline resistance and poor virologic control. Notably, minority variants, undetectable by standard assays, also appeared to influence viral replication and treatment failure, underscoring the need to detect both variant types when evaluating ART effectiveness.\u003c/p\u003e \u003cp\u003eProlonged use of NRTI- and NNRTI-based regimens has contributed to widespread HIVDRMs within these drug classes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In our cohort, common mutations included NRTI-associated M184VI, K65R, and K219QE, and NNRTI-associated K103NS and G190ASE (Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003ea), which confer resistance to the widely used agents such as 3TC, AZT, TDF, and EFV. These mutations were observed in both majority and minority variants, suggesting selective pressure from extensive drug exposure and transmission of resistant strains (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In contrast, PIs and INSTIs showed low levels of majority HIVDRMs but relatively higher levels of minority variants, likely reflecting their more limited use in first-line therapy. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHIVDRMs present at ART initiation can support ongoing viral replication, resulting in low-level viremia or viral blips, known predictors of future virologic failure (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In this study, individuals with pretreatment HIVDRMs were more likely to experience virologic failure compared to those without resistance (OR\u0026thinsp;=\u0026thinsp;5.29), although this association did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.224). The high rate of virologic failure among participants with baseline resistance (91%, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea) suggests a biologically meaningful trend that may have been underpowered due to sample size constraints. While the clinical significance of minority variants remains an area of ongoing investigation, our findings suggest they may contribute to suboptimal virologic outcomes. These findings support the utility of baseline resistance testing to guide individualized ART selection, particularly in settings where archived mutations may re-emerge under drug pressure (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy limitations\u003c/h2\u003e \u003cp\u003eA substantial proportion of participants did not complete the 24-month follow-up, primarily due to SARS-CoV-2\u0026ndash;related movement restrictions, resulting in a reduced sample size and limited statistical power. Additionally, the study was conducted in a central region with relatively better access to healthcare services, which may limit generalizability to populations in more remote settings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePretreatment HIVDRMs, including minority variants, may adversely affect virologic outcomes, although no statistically significant association was observed in this study. These findings highlight the importance of ongoing surveillance of pretreatment drug resistance. Where feasible, baseline resistance testing could improve ART selection and help mitigate the risk of treatment failure\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e3TC: lamivudine\u003c/p\u003e\n\u003cp\u003eAIDS: Acquired immunodeficiency syndrome\u003c/p\u003e\n\u003cp\u003eART: antiretroviral therapy\u003c/p\u003e\n\u003cp\u003eARV: antiretroviral\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAZT: Zidovudine\u003c/p\u003e\n\u003cp\u003eCFAR: Center for AIDS research\u003c/p\u003e\n\u003cp\u003eCp/ml : copies per milliliter\u003c/p\u003e\n\u003cp\u003eDNA: deoxyribonucleic acid\u003c/p\u003e\n\u003cp\u003eEFV: Efavirenz\u003c/p\u003e\n\u003cp\u003eHIV: Human immunodeficiency virus\u003c/p\u003e\n\u003cp\u003eHIVDR: HIV drug resistance\u003c/p\u003e\n\u003cp\u003eHIVDRMs: HIV-1 drug resistance mutations\u003c/p\u003e\n\u003cp\u003eINSTIs: integrase strand transfer inhibitors\u003c/p\u003e\n\u003cp\u003eJCRC: Joint Clinical Research Centre\u003c/p\u003e\n\u003cp\u003eKCCA: Kampala City Council Authority\u003c/p\u003e\n\u003cp\u003eNGS: next-generation sequencing\u003c/p\u003e\n\u003cp\u003eNNRTIs: nonnucleoside reverse transcriptase inhibitors\u003c/p\u003e\n\u003cp\u003eNRTIs: nucleoside reverse transcriptase inhibitors\u003c/p\u003e\n\u003cp\u003eNVP: Nevirapine\u003c/p\u003e\n\u003cp\u003ePCR: Polymerase chain reaction\u003c/p\u003e\n\u003cp\u003ePDR: Pretreatment HIV-1 drug resistance\u003c/p\u003e\n\u003cp\u003ePIs: protease inhibitors\u003c/p\u003e\n\u003cp\u003ePLWH: people living with HIV-1\u003c/p\u003e\n\u003cp\u003eRNA: ribonucleic acid\u003c/p\u003e\n\u003cp\u003eTDF:tenofovir\u003c/p\u003e\n\u003cp\u003eTLD: tenofovir/lamuvidine/doultegravir\u003c/p\u003e\n\u003cp\u003eTLE: tenofovir/lamuvidine/Efavirenz\u003c/p\u003e\n\u003cp\u003euL: microliter\u003c/p\u003e\n\u003cp\u003eVL: viral load\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the principles of the Declaration of Helsinki. The study was approved by the Research and Ethics Committee (REC) at JCRC and the Uganda National Council for Science and Technology.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants prior to enrollment in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Availability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset(s) supporting the conclusions of this article is(are) available in the GenBank repository under the accession number PP995671 - PP995775\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Case Western Reserve University/University Hospitals Center for AIDS Research developmental grant (A1036219:RES508058).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCenter for AIDS Research Uganda Laboratories, Joint Clinical Research Centre, Kampala, Uganda\u003c/p\u003e\n\u003cp\u003eFred Kyeyune, Eva Nabulime, Pamela Ainembabazi , William Tamale , Joel Kabali , Alisen Ayitewala , Immaculate Nankya\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorresponding author: Fred Kyeyune, Center For AIDS Research, Case Western Reserve University Cleveland Ohio and Joint Clinical Research Centre Uganda Tel:+256786224191 ([email protected])\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eF.K. and I.N. designed and oversaw the implementation of the study, data analysis and manuscript writing; T.W. was the study doctor and enrolled the patients; P.A., J.K., E.N., A.A., F.K. and I.N. performed the laboratory experiments and data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the people living with HIV-1 who participated in this study, staff from the Kampala City Council Authority and Joint Clinical Research Centre clinics\u0026rsquo; outpatient departments, and advisors from both Joint Clinical Research and the Center for AIDS Research, Case Western Reserve University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare they have no competing interests\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWeiser B,SB,KK,BH,MH,SQ,GW,RE,HS,ST,GA,AK,\u0026amp;RC. Long-term antiretroviral therapy mitigates mortality and morbidity independent of HIV tropism: 18 years follow-up in a women\u0026apos;s cohort. AIDS (London, England). 2022; 36(14): p. 1979\u0026ndash;1986.\u003c/li\u003e\n\u003cli\u003eZhang T,LL,SY,FY,RY,\u0026amp;XH. Relationship Between Drug Resistance and Death in HIV-Infected Patients Receiving Antiretroviral Therapy - 7 PLADs, China, 2010-2019. 2021; 3(14): p. 291\u0026ndash;297.\u003c/li\u003e\n\u003cli\u003eMacdonald V,ML,JMR,MB,JS,BR,VA,\u0026amp;BS. Prevalence of pretreatment HIV drug resistance in key populations: a systematic review and meta-analysis. Journal of the International AIDS Society. 2020; 23(12): p. e25656.\u003c/li\u003e\n\u003cli\u003eShafer RW,\u0026amp;VDA. Highly active antiretroviral therapy (HAART) for the treatment of infection with human immunodeficiency virus type 1. Biomedicine \u0026amp; pharmacotherapy. 1999; 53(2): p. 73\u0026ndash;86.\u003c/li\u003e\n\u003cli\u003eBello KJ,MO,OTA,WSH,LT,GA,ABK,\u0026amp;OJF. Factors associated with 10 years of continuous viral load suppression on HAART. BMC infectious diseases. 2016; 16: p. 351.\u003c/li\u003e\n\u003cli\u003eKyeyune F,GRM,NI,VC,MS,AJ,NE,KCM,SRA,MP,AEJ,\u0026amp;QMME. Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure. Antimicrobial agents and chemotherapy. 2016; 60(6): p. 3380\u0026ndash;3397.\u003c/li\u003e\n\u003cli\u003eVan Vaerenbergh K. Study of the impact of HIV genotypic drug resistance testing on therapy efficacy. Verh K Acad Geneeskd Belg. 2001; 63(5): p. 447-73.\u003c/li\u003e\n\u003cli\u003eBalakrishna S,LT,ZM,FP,HM,KK,YS,LK,PM,RA,WC,FC,KP,GA,HHH,SM,RA,CM,BE,N. Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1. The Journal of antimicrobial chemotherapy. 2023; 78(3): p. 656\u0026ndash;664.\u003c/li\u003e\n\u003cli\u003eMohamed S,BR,\u0026amp;SC. From Capillary Electrophoresis to Deep Sequencing: An Improved HIV-1 Drug Resistance Assessment Solution Using In Vitro Diagnostic (IVD) Assays and Software. Viruses. 2023; 15(2): p. 571.\u003c/li\u003e\n\u003cli\u003eHermans LE,HLM,SR,THR,BDM,TSAJ,DJD,THA,VWDF,NM,\u0026amp;WAMJ. HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment. AIDS (London, England). 2022; 36(7): p. 923\u0026ndash;931.\u003c/li\u003e\n\u003cli\u003eTaylor T,LER,NM,EE,LB,CR,GMK,DGV,SP,BJ,\u0026amp;JH. A MiSeq-HyDRA platform for enhanced HIV drug resistance genotyping and surveillance. Scientific reports. 2019; 9(1): p. 8970.\u003c/li\u003e\n\u003cli\u003eW. SR. Rationale and uses of a public HIV drug-resistance database. The Journal of infectious diseases. 2006; 194(S51\u0026ndash;S58): p. S51\u0026ndash;S58.\u003c/li\u003e\n\u003cli\u003ePineda-Pe\u0026ntilde;a AC,FNR,IS,LP,AAB,DK,GLA,CRJ,dOT,\u0026amp;VAM. Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools.. journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2013; 19: p. 337-348.\u003c/li\u003e\n\u003cli\u003eWHO. WHO releases HIV drug resistance report 2021. Geneva:; 2021.\u003c/li\u003e\n\u003cli\u003eOrganization WH. CONSOLIDATED GUIDELINES FOR THE PREVENTION AND TREATMENT OF HIV AND AIDS.; 2021. Available from: https://elearning.idi.co.ug/wp-content/uploads/2022/05/Consolidated-Guidelines-for-the-Prevention-and-Treatment-of-HIV-and-AIDS-in-Uganda-2020.pdf.\u003c/li\u003e\n\u003cli\u003eBoender TS,HBM,SKC,HRL,WM,ST,SM,LMEE,NI,KCM,ATA,AAS,MK,BME,OP,\u0026amp;RdWTF. Pretreatment HIV drug resistance increases regimen switches in sub-Saharan Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015; 61(11): p. 1749\u0026ndash;1758.\u003c/li\u003e\n\u003cli\u003eAyitewala A KFAPNEKCNI. Comparison of HIV drug resistance profiles across HIV-1 subtypes A and D for patients receiving a tenofovir-based and zidovudine-based first line regimens in Uganda. AIDS Res Therapy. 2020; 17(1): p. 2.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"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":"pretreatment HIV drug resistance, minority variants, next-generation sequencing","lastPublishedDoi":"10.21203/rs.3.rs-9308576/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9308576/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePretreatment HIV-1 drug resistance (PDR), including minority variants, may compromise antiretroviral therapy (ART) outcomes but remains underexplored in non-B HIV-1 subtypes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis longitudinal study enrolled 106 ART-na\u0026iuml;ve Ugandan adults (2018\u0026ndash;2020) to assess the impact of majority (\u0026ge;\u0026thinsp;20%) and minority (\u0026lt;\u0026thinsp;20%) pretreatment HIV-1 drug resistance mutations on virologic outcomes using next-generation sequencing of baseline HIV-1 RNA. Viral load was measured at 6, 12, and 24 months, and associations between PDR and cumulative viral load were evaluated among 38 participants with complete follow-up.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMajority HIVDRMs were most frequent in NNRTIs and NRTIs, while minority variants were more common in PIs and INSTIs. Among participants with complete follow-up, 26% had detectable cumulative VL, of whom 91% harbored at least one HIVDRM. PDR was not significantly associated with detectable VL (OR\u0026thinsp;=\u0026thinsp;5.29, 95% CI: 0.58\u0026ndash;48.20; p\u0026thinsp;=\u0026thinsp;0.224), although a trend toward poorer virologic outcomes was observed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePretreatment HIVDRMs, may adversely affect virologic outcomes, although no statistically significant association was observed. Expanding access to baseline resistance testing could improve ART selection and treatment outcomes in settings with diverse HIV-1 subtypes.\u003c/p\u003e","manuscriptTitle":"Brief Communication: Impact of Pretreatment HIV-1 Drug Resistance on Virologic Outcomes in Ugandan Patients infected with Non-B HIV-1 Subtypes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 08:08:53","doi":"10.21203/rs.3.rs-9308576/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-08T08:35:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-24T18:50:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-21T19:55:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53354384560307863217897073132270797919","date":"2026-04-10T19:23:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"49938191533535491645497382055452327081","date":"2026-04-10T19:08:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31702799256650998804542745450793667442","date":"2026-04-09T06:55:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"277141943900737958887967951739373086425","date":"2026-04-09T01:21:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-08T18:51:19+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-08T16:36:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-08T09:11:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-08T09:10:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-04-03T03:59:55+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":"4a25a593-ceda-4557-bee3-56840824c252","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-08T08:35:01+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-08T08:41:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 08:08:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9308576","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9308576","identity":"rs-9308576","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}