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Objective: HIV drug resistance (HIVDR) has become a threat to the elimination of the AIDS epidemic due to the global scale-up of antiretroviral therapy (ART) for HIV-infected individuals. This study aims to investigate the epidemiological dynamics and molecular characterization of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hangzhou, a developed region in China. Methods: An epidemiological survey combined with a molecular transmission network and Bayesian analysis was conducted. A total of 3,596 individuals with newly confirmed HIV infections (from 2020 to 2023) and 164 individuals with ART failure (from 2021 to 2023) were included. The molecular transmission network was used to identify key drug-resistant transmission clusters, while the Bayesian analysis was utilized to trace the origins and spread of these clusters. Results: The overall prevalence of PDR was found to be 8.4% (303/3596). Among these cases, PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) accounted for 4.7% (170/3596), significantly higher than the resistance observed for protease inhibitors (PIs; 2.8%, p < 0.001) and nucleoside reverse transcriptase inhibitors (NRTIs; 1.4%, p < 0.001). Multivariate logistic regression analysis revealed a significantly higher PDR value among individuals infected with the CRF07_BC subtype compared to those with the CRF08_BC subtype (aOR = 0.56, 95% CI = 0.359-0.859, p = 0.008). The molecular transmission network analysis identified the transmission of the drug resistance mutation (DRM) Q58E within the clusters of the CRF07_BC subtype. The Bayesian analysis suggested that these clusters were introduced into Hangzhou from Shenzhen between 2005 and 2012. Furthermore, the study highlighted 50.6% (83/164) prevalence of ADR among individuals experiencing ART failure. The combined molecular network analysis of virological failure and newly confirmed HIV infections indicated the transmission of the K103N mutation between these groups. Conclusion: In conclusion, targeted interventions may be necessary for specific subtypes and transmission clusters to control the spread of drug-resistant HIV. Continuous monitoring of resistance patterns is critical to inform treatment strategies and optimize ART regimens. [ABSTRACT FROM AUTHOR]

Background: Prospective data on the effectiveness of resistance testing in informing treatment decisions and outcomes in with first-line failure in these settings is limited. This study aimed to assess the virological impact of HIV drug-resistance testing in patients with virological failure in Tanzania. Methods: Participants were randomly assigned to either the control or the experimental group. In addition to the standard of care, patients in the experimental group had access to genotypic drug-resistance testing, information used during treatment change and were followed up at six-and 12-months to determine virological suppression. Results: A total of 261 patients with a median age of 32 (14.7–44.7) years were enrolled. In the intention-to-treat analysis, at 6-months, suppression was achieved in 58 (42.3%; 95% CI, 34.1–50.1) experimental group patients versus 51 (41.1%; 95% CI, 32.5–49.8) control group patients, with a p-value of 0.4. At-12 months, suppression was achieved in 110 (80.3%; 95% CI, 73.6–87) experimental patients versus 99 (79.8%; 95% CI, 72.8–86.9) control patients, with a P-value of 0.5. In the per-protocol analysis, at 6-months, suppression was observed in 38.46% (95% CI, 27.6–49.3) experimental patients versus 38.6% (95% CI, 26.0–51.2) control patients, with a P-value of 0.5. At 12-months, suppression was observed in 79.49% (95% CI, 70.5–88.5) of experimental patients versus 75.44% (95% CI, 64.3–86.6) of control patients, with a P-value of 0.3. Conclusion: Conducting HIV drug-resistance testing, and switch to individualised second-line regimens did not significantly improve virological suppression in patients experiencing first-line ART failure in Tanzania.

Background Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on nonnucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics. Methods We conducted a prospective cohort study of PWH aged ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24 and 48 weeks later. The primary end point was viral suppression (<200 copies/mL) at 48 weeks. We collected blood for retrospective viral load (VL) assessment and conducted genotypic resistance tests for specimens with VL >500 copies/mL. Results We enrolled 500 participants (median age 47 years; 41% women). At 48 weeks after TLD transition, 94% of participants were in care with a VL <200 copies/mL (n = 469/500); 2% (n = 11/500) were lost from care or died; and only 2% (n = 9/500) had a VL >500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events. Conclusions High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region. Clinical Trials Registration NCT04066036. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing for HIV genotypic drug resistance testing (GRT). This work evaluated the concordance among different NGS-GRT interpretation tools in a real-life setting. Methods: Routine NGS-GRT data were generated from viral RNA at 11 Italian laboratories with the AD4SEQ HIV-1 Solution v2 commercial kit. NGS results were interpreted by the SmartVir system provided by the kit and by two online tools (HyDRA Web and Stanford HIVdb). NGS-GRT was considered valid when the coverage was >100 reads (100×) at each PR/RT/IN resistance-associated position listed in the HIVdb 9.5.1 algorithm. Results: Among 629 NGS-GRT, 75.2%, 74.2%, and 70.9% were valid according to SmartVir, HyDRA Web, and HIVdb. Considering at least two interpretation tools, 463 (73.6%) NGS-GRT had a valid coverage for resistance analyses. The proportion of valid samples was affected by viremia <10,000–1000 copies/mL and non-B subtypes. Mutations at an NGS frequency >10% showed fair concordance among different interpretation tools. Conclusion: This Italian survey on NGS resistance testing suggests that viremia levels and HIV subtype affect NGS-GRT coverage. Within the current routine method for NGS-GRT, only mutations with frequency >10% seem reliably detected across different interpretation tools. [ABSTRACT FROM AUTHOR]

HIV epidemics still exist as a major global public health burden, especially in middle- and low-income countries. Given the lack of approved vaccines, antiretroviral therapy (ART) remains the primary approach to reduce the mortality and morbidity linked to this disease. Effective treatment for HIV-1 requires the simultaneous administration of multiple drugs. However, the virus can show resistance to antiretroviral drugs, resulting in treatment failure. Therefore, this study focused on assessing the prevalence of mutations within the Indian HIV-positive population. After assessing the data, we intended to identify the most effective highly active ART (HAART) regimens for individuals with drug-resistant variants. Furthermore, our analysis revealed a spectrum of HIV mutations, with varying effects on protein stability. The significance of this analysis lies in its potential to optimize HAART selection for HIV-positive individuals by accounting for both prevalence and stability-altering mutations. By considering mutation effects on protein stability, we can modify treatment regimens, increasing the likelihood of therapy success and diminishing the risk of resistance. Moreover, this study contributes to the broader field of drug repurposing, offering insights into the rational design of antiretroviral therapies. [ABSTRACT FROM AUTHOR]

Background Resistance to antiretrovirals against human immunodeficiency virus (HIV) poses a threat to zero transmission of HIV by 2030. Few studies have been conducted on HIV drug resistance (HIVDR) mutations targeting adolescents. We determined the prevalence, pattern of HIVDR mutations, and factors associated with unsuppressed HIV viral load among adolescents on antiretroviral therapy (ART). Methods From March to June 2020, we conducted a cross-sectional study at the Infectious Disease Clinic in Dar es Salaam, Tanzania. HIV‐1 viral load was tested using m2000rt Real-Time HIV‐1 assay. A sample with a viral load equal or more than 1,000 copies/ml was tested for HIVDR mutations. We determined the factors associated with unsuppressed viral load using logistic regression. A p-value less than 0.05 was considered significant. Results We enrolled 131 participants with a median age (interquartile range) of 15 (13–18) years. Of all, 24(18.3%) had a viral load above 1000 copies/ml. HIVDR mutations were found in 19/24(68.4%). Mutation to protease inhibitors, nucleotide reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were 1(5.2%), 9(47.4%), and 11(57.9%), respectively. Non-antiretroviral therapy and orphanages were independently associated with unsuppressed viral load. Conclusion The prevalence of HIVDR and unsuppressed HIV viral load among adolescents are relatively high. The use of non-antiretroviral therapy and orphanage influenced the persistence of high viral load. Strategies for surveillance of HIVDR early warning signs should be devised among adolescents.

Summary: Background: Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level. Methods: We systematically searched PubMed, Embase, and Web of Science for studies reporting HIVDR in treatment-naive and treatment-experienced children and adolescents from inception to June 28, 2024. Eligible studies reported at least ten successfully genotyped cases. We excluded studies where drug resistance was not reported separately for children and adults or for treatment-naive and treatment-experienced populations. The methodological quality of eligible studies was assessed, and random-effect models were used for meta-analysis to determine the pooled overall and regimen-specific prevalence of one or more HIVDR mutations in these populations globally, regionally, or at the country level. This study is registered with PROSPERO under the number CRD42023424483. Findings: Of 2282 records identified, 136 studies (28,539 HIV-1-infected children from 52 countries) were included for analysis. The overall prevalence of HIVDR is 26.31% (95% CI, 20.76–32.25) among treatment-naive children and 74.16% (95% CI, 67.74–80.13) among treatment-experienced children (p

Abstract Background Large language models (LLMs) that can efficiently screen and identify studies meeting specific criteria would streamline literature reviews. Additionally, those capable of extracting data from publications would enhance knowledge discovery by reducing the burden on human reviewers. Methods We created an automated pipeline utilizing OpenAI GPT-4 32 K API version “2023–05-15” to evaluate the accuracy of the LLM GPT-4 responses to queries about published papers on HIV drug resistance (HIVDR) with and without an instruction sheet. The instruction sheet contained specialized knowledge designed to assist a person trying to answer questions about an HIVDR paper. We designed 60 questions pertaining to HIVDR and created markdown versions of 60 published HIVDR papers in PubMed. We presented the 60 papers to GPT-4 in four configurations: (1) all 60 questions simultaneously; (2) all 60 questions simultaneously with the instruction sheet; (3) each of the 60 questions individually; and (4) each of the 60 questions individually with the instruction sheet. Results GPT-4 achieved a mean accuracy of 86.9% – 24.0% higher than when the answers to papers were permuted. The overall recall and precision were 72.5% and 87.4%, respectively. The standard deviation of three replicates for the 60 questions ranged from 0 to 5.3% with a median of 1.2%. The instruction sheet did not significantly increase GPT-4’s accuracy, recall, or precision. GPT-4 was more likely to provide false positive answers when the 60 questions were submitted individually compared to when they were submitted together. Conclusions GPT-4 reproducibly answered 3600 questions about 60 papers on HIVDR with moderately high accuracy, recall, and precision. The instruction sheet's failure to improve these metrics suggests that more sophisticated approaches are necessary. Either enhanced prompt engineering or finetuning an open-source model could further improve an LLM's ability to answer questions about highly specialized HIVDR papers.

Background: Large language models (LLMs) that can efficiently screen and identify studies meeting specific criteria would streamline literature reviews. Additionally, those capable of extracting data from publications would enhance knowledge discovery by reducing the burden on human reviewers. Methods: We created an automated pipeline utilizing OpenAI GPT-4 32 K API version "2023–05-15" to evaluate the accuracy of the LLM GPT-4 responses to queries about published papers on HIV drug resistance (HIVDR) with and without an instruction sheet. The instruction sheet contained specialized knowledge designed to assist a person trying to answer questions about an HIVDR paper. We designed 60 questions pertaining to HIVDR and created markdown versions of 60 published HIVDR papers in PubMed. We presented the 60 papers to GPT-4 in four configurations: (1) all 60 questions simultaneously; (2) all 60 questions simultaneously with the instruction sheet; (3) each of the 60 questions individually; and (4) each of the 60 questions individually with the instruction sheet. Results: GPT-4 achieved a mean accuracy of 86.9% – 24.0% higher than when the answers to papers were permuted. The overall recall and precision were 72.5% and 87.4%, respectively. The standard deviation of three replicates for the 60 questions ranged from 0 to 5.3% with a median of 1.2%. The instruction sheet did not significantly increase GPT-4's accuracy, recall, or precision. GPT-4 was more likely to provide false positive answers when the 60 questions were submitted individually compared to when they were submitted together. Conclusions: GPT-4 reproducibly answered 3600 questions about 60 papers on HIVDR with moderately high accuracy, recall, and precision. The instruction sheet's failure to improve these metrics suggests that more sophisticated approaches are necessary. Either enhanced prompt engineering or finetuning an open-source model could further improve an LLM's ability to answer questions about highly specialized HIVDR papers. [ABSTRACT FROM AUTHOR]

We evaluated the prevalence and correlates of HIV viral nonsuppression and HIV drug resistance (HIV-DR) in a cohort of people who inject drugs living with HIV (PWID-LH) and their sexual and injecting partners living with HIV in Kenya. HIV-DR testing was performed on participants with viral nonsuppression. Of 859 PWID-LH and their partners, 623 (72.5%) were on antiretroviral therapy (ART) ≥4 months and 148/623 (23.8%) were not virally suppressed. Viral nonsuppression was more common among younger participants and those on ART for a shorter duration. Among 122/148 (82.4%) successfully sequenced samples, 55 (45.1%) had detectable major HIV-DR mutations, mainly to non-nucleoside and nucleotide reverse transcriptase inhibitors (NNRTI and NRTI). High levels of HIV-DR among those with viral nonsuppression suggests need for viral load monitoring, adherence counseling, and timely switching to alternate ART regimens in this key population. [ABSTRACT FROM AUTHOR]

Objectives: The main objective of this analysis was to evaluate the impact of pre‐existing drug resistance by next‐generation sequencing (NGS) on the risk of treatment failure (TF) of first‐line regimens in participants enrolled in the START study. Methods: Stored plasma from participants with entry HIV RNA >1000 copies/mL were analysed using NGS (llumina MiSeq). Pre‐existing drug resistance was defined using the mutations considered by the Stanford HIV Drug Resistance Database (HIVDB v8.6) to calculate the genotypic susceptibility score (GSS, estimating the number of active drugs) for the first‐line regimen at the detection threshold windows of >20%, >5%, and >2% of the viral population. Survival analysis was conducted to evaluate the association between the GSS and risk of TF (viral load >200 copies/mL plus treatment change). Results: Baseline NGS data were available for 1380 antiretroviral therapy (ART)‐naïve participants enrolled over 2009–2013. First‐line ART included a non‐nucleoside reverse transcriptase inhibitor (NNRTI) in 976 (71%), a boosted protease inhibitor in 297 (22%), or an integrase strand transfer inhibitor in 107 (8%). The proportions of participants with GSS <3 were 7% for >20%, 10% for >5%, and 17% for the >2% thresholds, respectively. The adjusted hazard ratio of TF associated with a GSS of 0–2.75 versus 3 in the subset of participants with mutations detected at the >2% threshold was 1.66 (95% confidence interval 1.01–2.74; p = 0.05) and 2.32 (95% confidence interval 1.32–4.09; p = 0.003) after restricting the analysis to participants who started an NNRTI‐based regimen. Conclusions: Up to 17% of participants initiated ART with a GSS <3 on the basis of NGS data. Minority variants were predictive of TF, especially for participants starting NNRTI‐based regimens. [ABSTRACT FROM AUTHOR]

Despite effective antiretroviral therapies (ARTs), a subset of people living with HIV (PLWH) still experience low-level viremia (LLV, i.e., 50–1,000 copies/mL). The present study compared PLWH experiencing LLV with those maintaining virological suppression (VS) and explored the potential impact of preexisting drug resistance and other factors on LLV. We conducted a retrospective, 1:1 matched case–control study within a cohort of drug-experienced VS subjects from the Italian Antiviral Response Cohort Analysis database, followed in the period 2009–2019. Cases were individuals experiencing LLV, while controls were those who maintained VS. Matching was for calendar year of first ART regimen. Preexisting drug resistance was calculated as cumulative genotypic susceptibility score (GSS) according to regimen administered at the observational period start. To explore the effect of cumulative GSS, treated as a binary variable (≥2 and <2) and other factors on LLV, we performed a logistic regression analysis. Within a main population of 3,455 PLWH, 337 cases were selected. Cases were comparable to the controls for both gender and age. However, cases showed that they had experienced a longer time since HIV diagnosis, a higher number of drugs previously administered, lower baseline CD4+ T cell count and a higher zenith viral load (VL). By multivariate analysis, we found that higher zenith VL [adjusted odds ratio (aOR) (95% confidence interval [CI]) 1.30 (1.14–1.48)], a cumulative usage of both PI [aOR (95% CI): 2.03 (1.19–3.48)] and InSTI [aOR (95% CI): 2.23 (1.47–3.38)] and a cumulative GSS <2 [aOR (95% CI) 0.67 (0.46–0.98)], were associated with a higher risk in developing LLV. In current high-efficacy ART era, in drug-experienced PLWH, the predictors of increased risk of LLV were the presence of preexisting drug resistance, higher zenith VL, and previous PI, and InSTI exposure. [ABSTRACT FROM AUTHOR]

Background: Clinical trials of dapivirine (DPV) vaginal ring have shown it is safe, effective, and desired by women as an HIV prevention option. The risk of drug resistance is a potential concern for DPV ring users who acquire HIV. We conducted a comprehensive resistance evaluation of plasma samples from the women who seroconverted during the Microbicide Trials Network-025/HIV Open-label Prevention Extension (HOPE) study of DPV ring. Methods: Plasma collected on the visit at which seroconversion was detected was tested by next-generation sequencing with unique molecular identifiers for non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRM) present at ≥1% frequency. Bulk-cloned plasma-derived recombinant HIV was phenotyped in a TZM-bl–based assay for susceptibility to DPV and other NNRTI. HIV-1 RNA was retrospectively quantified in plasma samples collected before HIV seroconversion. Results: Among 38 participants who seroconverted in HOPE, 7 (18%) had NNRTI DRM detected by next-generation sequencing with unique molecular identifiers including A98G, K103N, V106M, E138A, and V179D. Six of 7 samples with NNRTI DRM had <3-fold reduction in susceptibility to DPV. Only 1 sample with K103N and V179I polymorphism had 9-fold reduction in susceptibility to DPV, but this genotype occurred in an individual who did not use DPV ring, likely indicating transmitted resistance. Detection of NNRTI resistance was not higher in individuals who remained on DPV ring >3 months after acquiring HIV infection. Conclusions: NNRTI resistance among women who seroconverted during HOPE was infrequent and selection of DPV-specific mutations was not detected. DPV ring is considered a safe and effective option for HIV prevention in women. [ABSTRACT FROM AUTHOR]

Background: The successful detection of drug-resistance mutations (DRMs) in HIV-1 infected patients has improved the management of HIV infection. Next-generation sequencing (NGS) to detect low-frequency mutations is predicted to be useful for efficiently testing minority drug resistance mutations, which could contribute to virological failure. This study employed Sanger sequencing and NGS to detect and compare minority and majority drug resistance mutations in HIV-1 strains in treatment-naive patients from Ghana. Method: From a previous study, 20 antiretroviral therapy (ART)-naive participants were selected for a cross-sectional study. Sanger sequencing and NGS techniques were used to detect the majority and minority HIV drug resistance (HIVDR) mutations, respectively, in the protease (PR) and partial reverse transcriptase (RT) genes. NGS detected mutations at 1 % and 5 % frequencies and Sanger sequencing at ≥20 % frequencies. The sequences obtained from NGS and Sanger sequencing platforms were submitted to the Stanford HIV drug resistance database for subtyping, mutation identification, and interpretations. Results: Sequences from the twenty participants where the CRF02_AG was the predominant strain (16, 80 %) were analyzed. NGS detected 25 mutations in the RT and PR genes, compared to 21 mutations by Sanger sequencing. Minority DRMs were detected at the prevalence of 55.0 % with NGS against 35 % DRMs by Sanger sequencing. One of the patients had eight different HIVDR variants, with two minority variants. These mutations were directed against PI (K20I and D30DN), NNRTI (Y181C, M23LM and V108I) and NRTI (K65R, M184I, and D67N). Conclusion: The study affirms the usefulness of genomic sequencing for drug resistance testing in HIV. It further shows that Sanger sequencing alone may not be adequate to detect mutations and that NGS capacity should be developed and deployed in the Ghanaian clinical settings for patients living with HIV.

Background: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing for HIV genotypic drug resistance testing (GRT). This work evaluated the concordance among different NGS-GRT interpretation tools in a real-life setting. Methods: Routine NGS-GRT data were generated from viral RNA at 11 Italian laboratories with the AD4SEQ HIV-1 Solution v2 commercial kit. NGS results were interpreted by the SmartVir system provided by the kit and by two online tools (HyDRA Web and Stanford HIVdb). NGS-GRT was considered valid when the coverage was >100 reads (100×) at each PR/RT/IN resistance-associated position listed in the HIVdb 9.5.1 algorithm. Results: Among 629 NGS-GRT, 75.2%, 74.2%, and 70.9% were valid according to SmartVir, HyDRA Web, and HIVdb. Considering at least two interpretation tools, 463 (73.6%) NGS-GRT had a valid coverage for resistance analyses. The proportion of valid samples was affected by viremia 10% showed fair concordance among different interpretation tools. Conclusion: This Italian survey on NGS resistance testing suggests that viremia levels and HIV subtype affect NGS-GRT coverage. Within the current routine method for NGS-GRT, only mutations with frequency >10% seem reliably detected across different interpretation tools.

Detection of HIV drug resistance (HIVDR) is vital to successful anti‐retroviral therapy (ART). HIVDR testing to determine drug‐resistance mutations is routinely performed in Australia to guide ART choice in newly diagnosed people living with HIV or in cases of treatment failure. In 2022, our clinical microbiology laboratory sought to validate a next‐generation sequencing (NGS)‐based HIVDR assay to replace the previous Sanger‐sequencing (SS)‐based ViroSeq. NGS solutions for HIVDR offer higher throughput, lower costs and higher sensitivity for variant detection. We sought to validate the previously described low‐cost probe‐based NGS method (veSEQ‐HIV) for whole‐genome recovery and HIVDR‐testing in a diagnostic setting. veSEQ‐HIV displayed 100% and 98% accuracy in major and minor mutation detection, respectively, and 100% accuracy of subtyping (provided > 1000 mapped reads were obtained). Pairwise comparison exhibited low inter‐and intrarun variability across the whole‐genome (Jaccard index [J] = 0.993; J = 0.972) and the Pol gene (J = 0.999; J = 0.999), respectively. veSEQ‐HIV met all our pre‐set criteria based on WHO recommendations and successfully replaced ViroSeq in our laboratory. Scaling‐down veSEQ‐HIV to a limited batch size and sequencing on Illumina iSeq. 100, allowed easy implementation of the assay into the workflow of a small sequencing laboratory with minimal staff and equipment and the ability to meet clinically relevant test turn‐around times. As HIVDR‐testing moves from SS‐ to NGS‐based methods and new ART drugs come to market (particularly those with targets outside the Pol region), whole‐genome recovery using veSEQ‐HIV provides a robust, cost‐effective and "future‐proof" NGS method for HIVDR‐testing. [ABSTRACT FROM AUTHOR]

The presence of human immunodeficiency virus (HIV) 1 subtype A6, characterized by the L74I integrase (IN) polymorphism, is associated with confirmed virologic failure in clinical trials of long-acting cabotegravir and rilpivirine. We investigated the effect of L74I on replication capacity (RC) of recombinant viruses carrying this polymorphism in combination with various IN stand-transfer inhibitor resistance mutations. The presence of L74I conferred greater RC to recombinant viruses expressing HIV-1 A6 IN when present together with G118R, G140R, Q148H, and R263K; no significant difference in RC was observed for the Q148K or R mutants. These findings may explain, in part, the association of HIV-1 subtype A6 with virologic failure. [ABSTRACT FROM AUTHOR]

Background HIV clinical practice guidelines outline broad treatment principles but offer less explicit recommendations by permutations of encountered viral resistance. We hypothesize that there is variability in antiretroviral (ARV) regimen decision making among providers when considering HIV drug resistance (HIVDR). Methods US HIV providers provided ARV regimen recommendations for case vignettes in a series of electronic surveys encompassing variations of HIVDR. Responses were characterized by drugs and classes selected and anticipated activity based on genotypic susceptibility. Heterogeneity was defined as the proportion of unique ARV regimens from total responses. Results An overall 119 providers from the United States participated. Among case vignettes with isolated M184V and viremia, 85.9% selected a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) + integrase strand transfer inhibitor (INSTI); 9.9% selected regimens with >3 ARVs. Alternatively, in scenarios of viremia with moderate to high-level NRTI resistance, >50% of providers selected an NRTI-sparing regimen, while a minority recommended 2 NRTIs + INSTI (21/123, 17%). In moderate to high-level INSTI resistance, there was response heterogeneity, with no common unifying approach to management (127 unique regimens/181 responses, 70% heterogeneity). Providers used cabotegravir/rilpivirine for treatment simplification in suppressed cases, despite a history of treatment failure (37/205, 36%). Conclusions Our national survey of US HIV providers revealed a consensus to management of HIV resistance with potential alternative options in cases with low heterogeneity. Providers selected cabotegravir/rilpivirine as a viable treatment simplification strategy in suppressed cases with a history of treatment failure. The responses to the case vignettes could be used an education tool for ARV decision making in HIVDR. [ABSTRACT FROM AUTHOR]

Background To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%–3.81%; interventional: 0.00%) and without (real-world: 0.73%–2.37%). Meta-analysis–estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00–.04], 0.03 [.01–.06], and 0.04 [.01–.07]; interventional: 0.00 [.00–.02], 0.00 [.00–.01], and 0.00 [.00–.03]) and without (real-world: 0.00 [.00–.02], 0.02 [.01–.04], and 0.02 [.00–.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I. Conclusions Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options. [ABSTRACT FROM AUTHOR]

Acquired drug resistance (ADR) is common among adolescents living with perinatal HIV (APHI) in sub-Saharan Africa (SSA). Personalized management has the potential to improve pediatric antiretroviral therapy (ART), even in the presence of long-term treatment and HIV-1 subtype diversity. We sought to evaluate the effect of HIV-1 mutational profiling on immuno-virological response and ADR among APHI. A cohort-study was conducted from 2018-2020 among 311 APHI receiving ART in Cameroon. Clinical, immunological and virological responses were measured at enrolment (T1), 6-months (T2) and 12-months (T3). Immunological failure (IF: CD4 <250 cells/mm3), VF (viremia =1,000 copies/ml), and ADR were analyzed, with P<0.05 considered significant. Mean age was 15(±3) years; male-female ratio was 1:1; median [IQR] ART-duration was 36[21-81] months. At T1, T2, and T3 respectively, adherence-level was 66.4, 58.3 and 66.5%; 14 viral clades were found, driven by CRF02_AG (58.6%); ADR-mutations favored increased switch to second-line ART (16.1, 31.2, and 41.9%, P<0.0001). From T1-T3 respectively, there were declining rates of IF (25.5, 18.9, and 9.83%, P<0.0001), VF (39.7, 39.9, and 28.2%, P=0.007), and HIVDR (96.4, 91.7, and 85.0%, P=0.099). Predictors of ADR were being on first-line ART (P=0.045), high viremia at enrolment (AOR=12.56, P=0.059), and IF (AOR=5.86, P=0.010). Of note, optimized ART guided by mutational profile (AOR=0.05, P=0.002) was protective. Moreover, full Tenofovir+Lamivudine+ Dolutegravir efficacy was predicted in 77 and 62% of APHI respectively after first- and second-line failure. Among APHI in this SSA setting, viral mutational profiling prompts the use of optimized Dolutegravir-based ART regimens, leading to improved immuno-virological response and declining ADR burdens. Thus, implementing personalized HIV medicine in this vulnerable population would substantially improve ART response and the achievement of the 95-95-95 goals in these underserved populations. [ABSTRACT FROM AUTHOR]

According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15–49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71–85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31–72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72–18.10%), and to NNRTIs in 44.26% (95% CI: 31.55–57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acquisition of HIV primary drug resistant (PDR) infection can lead to poor virologic and clinical outcomes in individuals and hampers public health efforts in epidemic control. Monitoring PDR in HIV-positive blood donors can be used to inform nationwide trends in the spread of drug-resistant HIV strains. METHODS: We conducted a cross-sectional study using genetic sequence analysis to assess HIV pol sequences, PDR, and risk factors for infection using audio computer-assisted structured interviews in four large blood centers in Brazil from 2007 to 2017. RESULTS: Of 716 HIV-positive blood donors, 504 (70.4%) were successfully sequenced. HIV clade B (73.2%) was the most prevalent subtype, followed by a mix of non-B (21.2%) sub-types. A twofold increase (from 4% to 8%) in recombinants prevalence was observed during the study period. Sixty-four (12.7%) presented PDR. Overall, HIV PDR prevalence remained stable during the study period. Drug resistance mutations for non-nucleoside reverse transcriptase inhibitors were found in 39 (7.7%) donors, while for nucleoside reverse transcriptase inhibitors were found in 26 (5.1%), and for protease inhibitors in 24 (4.8%) of HIV-infected donors. We did not find statistically significant differences in demographics, behavioural risk factors, or HIV genotypes when comparing volunteers with and without PDR. CONCLUSION: The HIV PDR rate among donors remained stable during the study period. HIV-positive blood donors can be an informative population to monitor primary HIV resistance and ultimately may help to increase the knowledge and awareness of HIV risk factors and PDR.

In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region. [ABSTRACT FROM AUTHOR]

Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log10 VL were 39 (29–48) years and 5.41 (4.80–5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25–30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: We investigated whether deep sequencing of archived HIV DNA of antiretroviral-naive persons with acute/early HIV infection could identify transmitted drug resistance mutations (DRM), per the IAS drug resistance algorithm, which are not detected by routine bulk (consensus) sequencing. Methods: Deep sequencing of HIV DNA from peripheral blood mononuclear cells and consensus sequencing from concurrent blood plasma (BP) was performed from antiretroviral (ART)-naive adults with recent infection. We compared the prevalence of low-frequency (2%–20%) and high-frequency (>20%) nonnucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) DRM. Results: Overall, 190 individuals were included, 72 (37.9%) with acute, 20 (10.5%) with very early, and 98 (51.6%) with recent HIV infection. Although all DRM detected in plasma appeared in archived proviral DNA, 9 high-frequency mutations were only detected in HIV DNA. These included 3 NRTI mutations, 4 NNRTI mutations, 1 PI mutation, and 1 H221Y (associated rilpivirine resistance) mutation. When considering DRM <20%, 11 NNRTI, 7 NRTI, 6 PI, and 3 F227L (associated doravirine resistance) mutations were found exclusively in HIV DNA. Interestingly, although 2 high-frequency M184V appeared in both DNA and RNA, low-frequency M184I were exclusive to HIV DNA (n = 6). No participants experienced virologic failure after initiating ART during the median 25.39 ± 3.13 months of follow-up on treatment. Conclusion: Although most high-frequency DRMs were consistently detected in HIV RNA and HIV DNA, the presence of low-frequency DRM in proviral DNA may be relevant for clinicians because these mutations could become dominant under drug selection pressure. [ABSTRACT FROM AUTHOR]

BACKGROUND:In low HIV prevalence settings, understanding the transmission dynamics and the impact of drug resistance are critical to curb down the epidemic. This study aims to explore the prevalence and dynamic of transmission of HIV drug resistance mutations (DRM) among key populations in Haiti. SETTINGS:Eligible participants (naïve, treated) were selected from 7 key-populations friendly healthcare centers in Port-au-Prince Haiti, from September 2018 to July 2019. METHODS:A total of 119 HIV-1 pol sequences were analyzed from men having sex with men (MSM), female sex workers (FSW) and their sexual partners. Screening for HIV DRM was performed using the Stanford University Drug Resistance Database. Phylogenetic and network analyses using HIV-TRACE software were performed to infer putative relationships and shared DRM. RESULTS:Of the 119 participants 62.2% were male (74/119), and 75.7% of them (56/74) reported MSM as main risk factor. The overall DRM prevalence was 58.8% (70/119). DRM was observed in 37.5% of MSM (21/56), 82.2% of FSWs (37/45) and 66.7% (12/18) among FSW clients. In a multivariate model, age and FSW were significant predictors for DRM (p=0.001). Transmission network analysis found 24/119 (20.2%) genetically linked individuals forming 8 clusters. Clustering participants were mostly MSM (15/24; 62.5%). Five clusters (62.5%) had shared DRM and K103N and M184V were the main shared mutations. CONCLUSION:High prevalence of HIV DRM was observed among MSM, FSW and their clients in Port-au-Prince Haiti. Network analysis revealed frequent DRM transmission among genetically linked individuals, highlighting the need for appropriate interventions to limit HIV transmission in these high-risk populations.

BACKGROUND:In low HIV prevalence settings, understanding the transmission dynamics and the impact of drug resistance are critical to curb down the epidemic. This study aims to explore the prevalence and dynamic of transmission of HIV drug resistance mutations (DRM) among key populations in Haiti. SETTINGS:Eligible participants (naïve, treated) were selected from 7 key-populations friendly healthcare centers in Port-au-Prince Haiti, from September 2018 to July 2019. METHODS:A total of 119 HIV-1 pol sequences were analyzed from men having sex with men (MSM), female sex workers (FSW) and their sexual partners. Screening for HIV DRM was performed using the Stanford University Drug Resistance Database. Phylogenetic and network analyses using HIV-TRACE software were performed to infer putative relationships and shared DRM. RESULTS:Of the 119 participants 62.2% were male (74/119), and 75.7% of them (56/74) reported MSM as main risk factor. The overall DRM prevalence was 58.8% (70/119). DRM was observed in 37.5% of MSM (21/56), 82.2% of FSWs (37/45) and 66.7% (12/18) among FSW clients. In a multivariate model, age and FSW were significant predictors for DRM (p=0.001). Transmission network analysis found 24/119 (20.2%) genetically linked individuals forming 8 clusters. Clustering participants were mostly MSM (15/24; 62.5%). Five clusters (62.5%) had shared DRM and K103N and M184V were the main shared mutations. CONCLUSION:High prevalence of HIV DRM was observed among MSM, FSW and their clients in Port-au-Prince Haiti. Network analysis revealed frequent DRM transmission among genetically linked individuals, highlighting the need for appropriate interventions to limit HIV transmission in these high-risk populations.

BACKGROUND:Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. METHODS:We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. RESULTS:Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. CONCLUSIONS:DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

Abstract Background We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum. Methods This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes. Results Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size. Conclusions There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study.

ABSTRACT: Objectives: The aim of this study was to assess the efficacy of dolutegravir plus lamivudine (DTG+3TC) in a large set of virologically suppressed HIV-1 infected individuals with or without past M184V mutation. Methods: This observational study included individuals who switched to DTG+3TC with ≥1 genotype before switch. Survival analysis was used to evaluate the role of past M184V on virological rebound (VR) or blips after DTG+3TC switch. Results: A total of 712 individuals followed in several clinical centres in France, Italy and Spain were analysed. Past M184V was present in 60 (8.4%) individuals. By 3 years after switch, the overall probability of VR and blips was 6.7% and 6.9%, respectively, without any statistical significance according to the presence/absence of past M184V. A significantly higher probability of VR was found in individuals harbouring M184V before DTG+3TC with a duration of virological suppression (Ts) ≤.3.5 years compared to others (M184V+Ts ≤.3.5 years: 22.7%; M184M+Ts ≤.3.5 years: 9.0%; M184V+Ts >3.5 years: 7.8%; M184M+Ts >3.5 years: 4.9%; P = 0.007). This finding was not confirmed in multivariable models adjusting for behavioural and demographic variables. Genotypic resistance test after VR under DTG+3TC was available for 8/39 individuals; one poorly adherent individual developed M184V. No resistance to INIs was found. Conclusion: In this retrospective observational study, the probability of VR and blips in patients switching to DTG+3TC was very low after 3 years of treatment regardless M184V. The effect of a short duration of previous virological suppression in individuals with M184V remains troubling and needs ad hoc clinical trials to be confirmed.

Introduction. As is currently known, the epidemic process in the Kaliningrad Region was mainly associated with the spread of the recombinant form of HIV-1 (CRF03_AB); however, regular HIV importations from other countries and continents has created favorable conditions for emergence and spread of various recombinant forms of the virus. The most complete information on the diversity of recombinant forms in the region is also necessary to understand the structure of drug resistance (DR). The aim of the study was to explore the HIV-1 genetic diversity in the Kaliningrad Region. Materials and methods. We studied 162 blood plasma samples obtained from patients from the Kaliningrad Region, both with confirmed virological failure of antiretroviral therapy (ART) and with newly diagnosed HIV infection. For reverse transcription and amplification of HIV genome fragments, diagnostic AmpliSense HIVResist-Seq. Results and discussion. The various recombinants between subtypes A and B (74%) were predominant in study group: recombinant was between CRF03_AB and subtype A (33.95%) and CRF03_AB-like (13.58%) were the most common. Among the pure subtypes of the virus, subtype A6 (16.67%). The circulation of subtypes B (3.70%) and G (1.23%) was also noted. Ninety-six patients (59.26%) were identified with at least one mutation associated with antiretroviral (ARV) drug resistance. Conclusion. The observed diversity of subtypes and recombinant forms of the virus implies that the new recombinants are actively emerging in the studied region, both between existing recombinant forms and pure subtypes, as well as between pure subtypes.

In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region.

ABSTRACT: Objectives: We evaluated virological response and resistance profiles in individuals who were virologically suppressed who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in real life. Methods: Survival analysis was used to assess probability of virological rebound (VR). Cumulative major resistance mutations (MRM) and cumulative genotypic susceptibility score (cGSS) were evaluated before the switch. Results: Overall, 283 individuals virologically suppressed for a median (interquartile [IQR]) time of 7 (3–9) y were analyzed. Of these, 20.8% were in first-line treatment, 13.1% were highly treatment-experienced (HTE), and 8.5% had experienced previous integrase inhibitor (INI)-failures. Before the switch, nucleotide reverse transcriptase inhibitor NRTI MRM prevalence was 29% (M184V:13.8%; any thymidine analogue mutation: 14.1%; K65R: 0.7%; K70E 0.4%); only three (2.1%) individuals showed INI major resistance mutations (Y143C/H/R [n = 1]; Y143C [n = 1]; N155H [n = 1]), and 82.0% of individuals received fully active B/F/TAF. Ninety-six wk after switch, the probability of VR was 5%, with only 12 events of VR at a median (IQR) viremia level of 284 (187–980) copies/mL, mainly transient. No significant associations between virological outcomes and genotypic susceptibility to B/F/TAF were observed. People who experienced previous INI failures showed a significantly higher adjusted hazard ratio (AHR [95% CI]) to experience VR under B/F/TAF (3.9 [1.1–13.4], P = 0.031). This AHR increased in people who experienced INI failures and received partially active B/F/TAF (5.5 [1.4–21.1], P = 0.013). Conclusion: Within 96 wk, a switch to B/F/TAF in individuals who were virologically suppressed ensured a very high rate of virological control in a clinical setting. Previous resistance alone did not affect B/F/TAF response. However, people who had previous INI failures were more prone to losing virological control under B/F/TAF.

The most common HIV-1 subtype in South Africa is subtype C, and detection of other subtypes is rare. We report the first known case of HIV-1 subtype CRF18_cpx identified in KwaZulu-Natal, South Africa, the epicenter of the HIV epidemic, through HIV drug resistance genotyping.The 31-year-old female patient was initiated on fixed dose combination (tenofovir, emtricitabine, efavirenz) in 2017, with failure to achieve virologic suppression. Change to second-line antiretroviral therapy (tenofovir, emtricitabine and ritonavir-boosted lopinavir) was made in 2018. Adherence was impacted by lopinavir-induced diarrhoea. In 2020, she was switched to zidovudine, lamivudine and ritonavir-boosted atazanavir. Virologic failure persisted, and HIV drug resistance genotyping in April 2021 showed multidrug resistance. Third-line regimen (tenofovir, lamivudine, dolutegravir and ritonavir-boosted darunavir) was commenced in May 2021 and virologic suppression was achieved.Co-incidentally we discovered from the HIV drug resistance sequence report that the patient was infected with HIV-1 subtype CRF18_cpx. Analysis of the HIV sequence using REGA HIV-1 Subtyping Tool confirmed sequence subtype assignment as HIV-1 CRF 18_cpx (bootstrap confidence = 90%). Subtyping was also confirmed with the COMET HIV-1 tool, HIV BLAST tool and phylogenetic analysis.Based on our incidental finding, CRF18_cpx may be circulating locally as the patient had no travel history. Introduction of non-subtype C and recombinant viruses are expected to have increased in South Africa due to increased travel. This highlights the need to characterize subtype diversity in South Africa, particularly in KwaZulu-Natal, as HIV subtype can influence pathogenesis, treatment response, drug resistance and efforts towards vaccine development.

Background: We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum. Methods: This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes. Results: Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size. Conclusions: There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study. [ABSTRACT FROM AUTHOR]

Background: Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype. Materials and methods: The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype. Results: A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs (8.4 in 100 patient-years follow-up, PYFU) and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33; p = 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27; p = 0.001), after adjusting for age, gender, baseline CD4 count and HIV-RNA, concurrent AIDS-defining event and months since HIV diagnosis. Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B (aHR 3.35; p = 0.011), C (aHR 8.10; p = 0.005), CRF02-AG (aHR 5.59; p = 0.006) and G (aHR 13.90; p < 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24; p = 0.035) and CRF01-AE (versus B; aHR 10.65; p = 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF. Conclusions: In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 (HIV-1) is characterized by a large degree of genetic variability because of high rates of recombination and mutation, sizable population sizes, and rapid replication. Therefore, this study investigated HIV-1 subtype distribution and the appearance of drug resistance mutations (DRMs) in viruses that are prevalent in Makassar, South Sulawesi, Indonesia. The HIV-1 pol, env, and gag genes were amplified from 63 infected individuals and sequenced for a subtyping analysis. CRF01_AE was identified as the predominant HIV-1 circulating recombinant form (CRF) in Makassar, South Sulawesi, Indonesia. Subtype B and recombinant viruses containing CRF01_AE, CRF02_AG, and/or subtype B gene fragments were also detected. Several major DRMs against non-nucleoside reverse transcriptase inhibitors were found among antiretroviral therapy (ART)-experienced subjects, whereas ART-naive subjects did not possess any transmitted drug resistance. The prevalence of DRMs was very high among ART-experienced subjects; therefore, further surveillance is required in this region. [ABSTRACT FROM AUTHOR]

Background: Molecular epidemiological approaches provide opportunities to characterize HIV transmission dynamics. We analyzed HIV sequences and virus load (VL) results obtained during routine clinical care, and individual's zip-code location to determine utility of this approach. Methods: HIV-1 pol sequences aligned using ClustalW were subtyped using REGA. A maximum likelihood (ML) tree was generated using IQTree. Transmission clusters with ≤3% genetic distance (GD) and ≥90% bootstrap support were identified using ClusterPicker. We conducted Bayesian analysis using BEAST to confirm transmission clusters. The proportion of nucleotides with ambiguity ≤0.5% was considered indicative of early infection. Descriptive statistics were applied to characterize clusters and group comparisons were performed using chi-square or t-test. Results: Among 2775 adults with data from 2014–2015, 2589 (93%) had subtype B HIV-1, mean age was 44 years (SD 12.7), 66.4% were male, and 25% had nucleotide ambiguity ≤0.5. There were 456 individuals in 193 clusters: 149 dyads, 32 triads, and 12 groups with ≥ four individuals per cluster. More commonly in clusters were males than females, 349 (76.5%) vs. 107 (23.5%), p < 0.0001; younger individuals, 35.3 years (SD 12.1) vs. 44.7 (SD 12.3), p < 0.0001; and those with early HIV-1 infection by nucleotide ambiguity, 202/456 (44.3%) vs. 442/2133 (20.7%), p < 0.0001. Members of 43/193 (22.3%) of clusters included individuals in different jurisdictions. Clusters ≥ four individuals were similarly found using BEAST. HIV-1 viral load (VL) ≥3.0 log10 c/mL was most common among individuals in clusters ≥ four, 18/21, (85.7%) compared to 137/208 (65.8%) in clusters sized 2–3, and 927/1169 (79.3%) who were not in a cluster (p < 0.0001). Discussion: HIV sequence data obtained for HIV clinical management provide insights into regional transmission dynamics. Our findings demonstrate the additional utility of HIV-1 VL data in combination with phylogenetic inferences as an enhanced contact tracing tool to direct HIV treatment and prevention services. Trans-jurisdictional approaches are needed to optimize efforts to end the HIV epidemic. [ABSTRACT FROM AUTHOR]

Abstract Background Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. Methods We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China’s national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7–50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. Results Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50–999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts

In vitro passage experiments are crucial to the development of antiretroviral (ARV) drugs. We created an online database containing data from 102 published studies in which HIV-1 or HIV-2 was cultured with increasing concentrations of the FDA-approved nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), integrase strand transfer inhibitors (INSTIs), protease inhibitors (PIs), capsid inhibitor (CAI) lenacapavir, and nucleoside RT translocation inhibitor (NRTTI) islatravir. We summarized the mutations selected in the subset of passage experiments with NRTIs lamivudine (3TC), emtricitabine (FTC), abacavir (ABC), tenofovir (TFV), and zidovudine (AZT), NNRTIs doravirine (DOR), efavirenz (EFV), and rilpivirine (RPV), INSTIs bictegravir (BIC), cabotegravir (CAB), and dolutegravir (DTG), and PIs atazanavir (ATV), darunavir (DRV), and lopinavir (LPV). Mutations selected in vitro were compared with those selected in persons receiving the same ARV. Twenty-seven studies described 89 experiments of wildtype isolates passaged with 3TC, FTC, ABC, TFV, or AZT; sixteen studies described 89 experiments passaged with EFV, RPV, or DOR; eleven studies described 76 experiments passaged with the INSTIs BIC, CAB, or DTG; six studies described 33 experiments passaged with ATV, LPV, or DRV. With several exceptions, mutations selected in two or more experiments were among the most common mutations selected in persons receiving the same ARV. We created a database of published ARV in vitro selection experiments. Mutations emerging from these experiments generally predict those observed in persons receiving the same ARV. However, there are notable differences in mutation frequencies between in vitro and in vivo settings. • An online database containing in vitro selection experiments of HIV drug resistance mutations from 102 studies. • HIV-1 or HIV-2 was cultured with 14 FDA-approved ARVs. • Mutations selected in vitro were compared with those selected in persons received same antiretrovirals. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation. Recent Findings: The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. Summary: As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention. [ABSTRACT FROM AUTHOR]

Background: Resistance to antiretrovirals against human immunodeficiency virus (HIV) poses a threat to zero transmission of HIV by 2030. Few studies have been conducted on HIV drug resistance (HIVDR) mutations targeting adolescents. We determined the prevalence, pattern of HIVDR mutations, and factors associated with unsuppressed HIV viral load among adolescents on antiretroviral therapy (ART)., Methods: From March to June 2020, we conducted a cross-sectional study at the Infectious Disease Clinic in Dar es Salaam, Tanzania. HIV-1 viral load was tested using m2000rt Real-Time HIV-1 assay. A sample with a viral load equal or more than 1,000 copies/ml was tested for HIVDR mutations. We determined the factors associated with unsuppressed viral load using logistic regression. A p -value less than 0.05 was considered significant., Results: We enrolled 131 participants with a median age (interquartile range) of 15 (13-18) years. Of all, 24(18.3%) had a viral load above 1000 copies/ml. HIVDR mutations were found in 19/24(68.4%). Mutation to protease inhibitors, nucleotide reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were 1(5.2%), 9(47.4%), and 11(57.9%), respectively. Non-antiretroviral therapy and orphanages were independently associated with unsuppressed viral load., Conclusion: The prevalence of HIVDR and unsuppressed HIV viral load among adolescents are relatively high. The use of non-antiretroviral therapy and orphanage influenced the persistence of high viral load. Strategies for surveillance of HIVDR early warning signs should be devised among adolescents.

Due to a limited range of effective treatment options, highly treatment-experienced (HTE) people with HIV (PWH) still struggle to maintain virological suppression and obtain an adequate immunological recovery. To increase the likelihood of virologic success, HTE PWH require an individualized treatment regimen based on cumulative genotypic resistance testing (GRT) data, potential drug-drug interactions, and adherence. From the PRESTIGIO Registry, we present a case of a 28-year-old man with vertically transmitted HIV-1 infection, on therapy with an ibalizumab-including regimen and desiring a treatment simplification. In January 2024, the patient was started on a lenacapavir-containing regimen along with optimized background therapy in an attempt to maintain sustained virological suppression, simplify antiretroviral regimen, and potentially increase CD4+ T-cell count. At six months follow-up evaluation, virological suppression was confirmed, and an increase in CD4+ T-cell count of 60 cells/μL was observed. Close follow-up of this patient is ongoing.

Objective: HIV drug resistance (HIVDR) has become a threat to the elimination of the AIDS epidemic due to the global scale-up of antiretroviral therapy (ART) for HIV-infected individuals. This study aims to investigate the epidemiological dynamics and molecular characterization of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hangzhou, a developed region in China., Methods: An epidemiological survey combined with a molecular transmission network and Bayesian analysis was conducted. A total of 3,596 individuals with newly confirmed HIV infections (from 2020 to 2023) and 164 individuals with ART failure (from 2021 to 2023) were included. The molecular transmission network was used to identify key drug-resistant transmission clusters, while the Bayesian analysis was utilized to trace the origins and spread of these clusters., Results: The overall prevalence of PDR was found to be 8.4% (303/3596). Among these cases, PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) accounted for 4.7% (170/3596), significantly higher than the resistance observed for protease inhibitors (PIs; 2.8%, p  < 0.001) and nucleoside reverse transcriptase inhibitors (NRTIs; 1.4%, p  < 0.001). Multivariate logistic regression analysis revealed a significantly higher PDR value among individuals infected with the CRF07&#95;BC subtype compared to those with the CRF08&#95;BC subtype (aOR = 0.56, 95% CI = 0.359-0.859, p  = 0.008). The molecular transmission network analysis identified the transmission of the drug resistance mutation (DRM) Q58E within the clusters of the CRF07&#95;BC subtype. The Bayesian analysis suggested that these clusters were introduced into Hangzhou from Shenzhen between 2005 and 2012. Furthermore, the study highlighted 50.6% (83/164) prevalence of ADR among individuals experiencing ART failure. The combined molecular network analysis of virological failure and newly confirmed HIV infections indicated the transmission of the K103N mutation between these groups., Conclusion: In conclusion, targeted interventions may be necessary for specific subtypes and transmission clusters to control the spread of drug-resistant HIV. Continuous monitoring of resistance patterns is critical to inform treatment strategies and optimize ART regimens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Sun, Zhang, Luo, Wu, Ye, Xu and Chen.)

Background: Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level., Methods: We systematically searched PubMed, Embase, and Web of Science for studies reporting HIVDR in treatment-naive and treatment-experienced children and adolescents from inception to June 28, 2024. Eligible studies reported at least ten successfully genotyped cases. We excluded studies where drug resistance was not reported separately for children and adults or for treatment-naive and treatment-experienced populations. The methodological quality of eligible studies was assessed, and random-effect models were used for meta-analysis to determine the pooled overall and regimen-specific prevalence of one or more HIVDR mutations in these populations globally, regionally, or at the country level. This study is registered with PROSPERO under the number CRD42023424483., Findings: Of 2282 records identified, 136 studies (28,539 HIV-1-infected children from 52 countries) were included for analysis. The overall prevalence of HIVDR is 26.31% (95% CI, 20.76-32.25) among treatment-naive children and 74.16% (95% CI, 67.74-80.13) among treatment-experienced children (p < 0.0001). HIVDR varied widely across subregion with the highest prevalence in Southern Africa (37.80% [95% CI, 26.24-50.08]) and lowest in South America (11.79% [95% CI, 4.91-20.84]) for treatment-naive children while highest in Asia (80.85% [95% CI, 63.76-93.55]) and lowest in Europe (54.39% [95% CI, 28.61-79.03]) for treatment-experienced children. The proportion of viral failure (VF) presented positive correlation with DR prevalence for treatment-experienced children, which increased from 61.23% (95% CI, 47.98-73.72) in proportion of VF <50%-81.17% (95% CI, 71.57-89.28) in proportion of 100%. Meta-regression analysis for both groups showed that only age (naive: p = 0.0005; treated: p < 0.0001) was the sources of heterogeneity. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistances were the most seen mutations among the treatment-naive group, with the HIVDR prevalence more than 10% in Southern Africa, Western and Central Africa, Eastern Africa, Asia, and North America. Both nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI resistances were commonly seen among the treatment-experienced group, varying from 36.33% (95% CI, 11.96-64.93) in North America to 77.54% (95% CI, 62.70-89.58) in South America for NRTI and from 39.98% (95% CI, 13.47-69.97) in Europe to 68.86 (95% CI, 43.91-89.17) in Asia for NNRTI, respectively., Interpretation: This study underscores the significant burden of HIVDR among children and adolescents worldwide, particularly pronounced in sub-Saharan Africa and low-income countries. It emphasizes the critical importance of surveillance in all HIV-1-infected children and advocates for the adoption of dolutegravir (DTG) or other optimal formulations as first-line ART in settings where NNRTI resistance exceeds the WHO's 10% threshold. DTG's high resistance barrier, potent antiviral efficacy, and favorable safety profile makes it a superior choice for managing drug-resistant HIV-1, surpassing traditional antiretroviral therapies., Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality (No. JCYJ20220531102202005) and the Natural Science Foundation of Guangdong Province (No. 2024A1515012118)., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).)

Abstract Introduction The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance. Methods We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country. Results The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9–7.1) in Mozambique and 25.3% (17.9–33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2–14) in Eswatini to 64% (26–85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0–0.11) but high in Namibia (0.48; 0.16–10.17), Eswatini (0.64; 0.23–11.8) and South Africa (1.21; 0.83–9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance. Conclusions This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART.

We report two cases of dolutegravir (DTG) resistance in highly treatment experienced patients. Monitoring for treatment failure and adherence support is important in highly treatment experienced patients taking DTG. What this study adds: Dolutegravir is the mainstay of HIV treatment programmes and emergence of drug resistance to DTG is of public health relevance.

According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15–49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71–85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31–72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72–18.10%), and to NNRTIs in 44.26% (95% CI: 31.55–57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection.

Dolutegravir (DTG) use in combination with tenofovir and lamivudine (TLD) is scaling up in Africa. However, HIV drug resistance (HIVDR) data to DTG remain scarce in Zimbabwe. We assessed the prevalence and genetic mechanisms of DTG resistance in people living with HIV initiating on TLD. A prospective cohort study was conducted between October 2021 and April 2023 among antiretroviral therapy (ART) naïve adults (≥18 years) attending care at an HIV clinic in Zimbabwe. Pre-treatment drug resistance (PDR) was assessed prior to TLD initiation and viral load (VL) outcome and acquired drug resistance (ADR) to TLD were described after 24 weeks follow-up. In total, 172 participants were enrolled in the study. The median (IQR) age and log10 VL were 39 (29–48) years and 5.41 (4.80–5.74) copies/mL, respectively. At baseline, no PDR to DTG was found. However, as previously reported, PDR to non-nucleotide reverse transcriptase inhibitor (NNRTI) was high (15%) whilst PDR to NRTI was low (4%). After a median duration of 27 (25–30) weeks on TLD, virological suppression (VL < 1000 copies/mL) was 98% and among the 2 participants with VL ≥ 1000 copies/mL, no ADR was found. HIVDR to DTG is rare among ART naïve individuals. DTG is more likely to address the problems of HIVDR in Africa.