Transmitted drug resistance (TDR) threatens the effectiveness of first-line antiretroviral therapy, yet contemporary regional data from the Aegean region of Türkiye remain limited. This study evaluated TDR prevalence, mutational profiles, and HIV-1 subtype distribution among treatment-naïve individuals. We conducted a single-center retrospective cohort study at a tertiary referral center in İzmir, Türkiye, including adults with confirmed HIV-1 infection who were antiretroviral-naïve at baseline between January 2017 and December 2024. Genotypic resistance testing was performed before treatment initiation using Sanger sequencing. Resistance mutations were interpreted with Stanford HIVdb v10.1, and TDR was defined as a penalty score of ≥ 10 for at least one drug. A total of 163 individuals were included; the mean age was 38.16 ± 12.48 years, 91.4% were male, and subtype B was the most common clade (50.3%). Overall, 29 individuals (17.8%) had at least one resistance-associated mutation. NNRTI resistance predominated (15.3%), followed by NRTI (1.8%) and PI (0.6%); no INSTI mutations were detected. HIV-1 subtype F remained independently associated with antiretroviral resistance in multivariable logistic regression (OR 31.4, 95% CI 6.10-335.1; p < 0.001). E138A was the most common NNRTI substitution (7.4%). S68G was the most frequent accessory mutation, identified in 41.7% of patients. Transmitted drug resistance remains clinically relevant in treatment-naïve individuals in the Aegean region of Türkiye and is driven predominantly by NNRTI-associated mutations. The absence of baseline INSTI resistance supports the preserved activity of contemporary INSTI-based first-line regimens, while the observed association between subtype F and resistance warrants further molecular surveillance.

The elimination of mother-to-child transmission of human immunodeficiency virus (HIV) is a key global public health priority. In Africa, virologic failure among people living with HIV continues to pose a significant public health challenge, affecting both individual well-being and community health. Maintaining viral load suppression is crucial to prevent vertical transmission of HIV and to minimize maternal morbidity and mortality. To stop the vertical transmission of HIV and lower the risk of maternal morbidity and mortality, it is important to achieve viral load suppression. Although many African countries have adopted the global 95-95-95 targets, comprehensive data on virologic suppression among pregnant and lactating mothers across the continent remains limited. The objective of this systematic review and meta-analysis was to determine the pooled estimate of virologic suppression and to examine the factors associated with it among HIV-positive pregnant and lactating women on antiretroviral therapy in Africa. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251186121). We carried out a thorough systematic review by examining PubMed, ScienceDirect, Hinari, and Google Scholar for relevant studies. Data from the studies were retrieved using an Excel sheet and analyzed with STATA version 17. The Joanna Briggs Institute appraisal tool was used to evaluate the methodological quality of studies. A random-effects model with restricted maximum likelihood (REML) was applied to determine the pooled prevalence of virologic suppression (viral load threshold ≤1000 copies/ml) among pregnant and lactating mothers in Africa. A funnel plot and the Egger's test were used to investigate publication bias. Statistical heterogeneity was assessed using the I2statistic and Cochrane's Q test. A total of 55 eligible studies, comprising 304,883 participants, were included in the quantitative meta-analysis. Accordingly, the overall prevalence of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was 80.86% (95% CI: 77.63%, 84.09%, I2 = 99.84%). In contrast, the pooled estimate for achieving an undetectable viral load was substantially lower, at 60.92% (95% CI: 52.46%, 69.39%; I2 = 99.91%). Virologic suppression was significantly associated with women's age (15-24 years) (AOR = 0.49; 95% CI: 0.32-0.77), disclosure of HIV status to a partner (AOR = 1.66; 95% CI: 1.31-2.11), first-line antiretroviral therapy regimen (AOR = 6.53; 95% CI: 1.93-22.06), and good antiretroviral drug adherence (AOR = 3.61; 95% CI: 1.18-11.02). In addition, other socio-demographic variables, higher educational level, being married/cohabitant, urban residency, healthcare utilization (time of ANC booking, time of ART initiation, duration of ART), fear of stigma, distance to health facility, shortage of health professionals, ART drug stock-out, and lack of HIV care commodities were significantly associated with virologic suppression among HIV-positive pregnant and lactating women in Africa. The pooled estimate of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was approximately 81%, below the global target of 95% virological suppression. This emphasizes the necessity of targeted strategies for younger HIV-positive women, disclosing HIV status, initiating first-line antiretroviral regimens, and promoting antiretroviral treatment adherence. Upgrading health care systems to enable regular viral load monitoring, as well as addressing socio-demographic and antiretroviral therapy-related variables, are vital steps towards attaining and sustaining VS in these groups of population, ultimately assisting in achieving elimination of MTCT of HIV.

Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. 381 children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR:6.5,14.0, 67<3 years), CD4% 20% (IQR:12, 28), BMI-for-age Z-score -0.58 (IQR:-1.48,+0.25). 189 children started DTG, 192 started SOC (91%≥3 years started efavirenz; 79%<3 years started lopinavir). 75 children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (HR=0.47, 95%CI:0.29-0.77, p=0.002). Lower BMI-for-age Z-score (HR=0.82 for each unit gain, 95%CI:0.70-0.96, p=0.01) and being at an African site (HR=2.09, 95%CI:0.82-5.31, p=0.09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children, and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4%=20, hazard ratios relative to age 10 years were 2.40 (95%CI: 1.58-3.65) at age 1 year, 1.30 (95%CI: 1.15-1.48) at age 5 years and 0.80 (95%CI: 0.72-0.89) at age 18 years. At age 1 year, hazard ratios relative to CD4%=20 were 1.39 (95%CI: 1.16-1.66) at CD4%=15, and 0.52 (95%CI: 0.36-0.75) at CD4%=30; at age 10 corresponding estimates were 1.07 (95%CI: 0.94-1.20) at CD4%=15, and 0.88 (95%CI: 0.69-1.13) at CD4%=30. Young age, low BMI-for-age and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) recommended for first-line antiretroviral therapy (ART), and for suppressed switching, in combination with a two nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone. Doravirine does not have a high barrier to resistance, and genotypic resistance testing (GRT) pre-switch is recommended. Data on its use without pre-switching GRT is limited. This retrospective cohort study presents data on doravirine use in virologically suppressed people with and without prior GRT. A retrospective single centre review of health records was conducted among prescribed doravirine-based ART at a London HIV service. Of the 582 adults included, 75% were men, 56% were of White ethnicity. The median age at baseline was 51-years (IQR: 44-58). Median time on doravirine was 127-weeks (IQR:93-175). GRT showing no doravirine resistance was available for 78% (n = 454) of individuals before switching to doravirine, of which, 2% experienced virological failure (n = 9); including two people with NNRTI and NRTI resistance. Among those without pre-switching GRT (n = 97), 1% experienced virological failure (n = 1), with NNRTI and NRTI resistance. There was no statistical significant difference in virologic suppression (viral load <50 copies/ml) rates (GRT 95% versus no-GRT 95%; p = 0.823). A similar proportion of people with (24%) and without (27%) pre-switching GRT switched away from doravirine, most commonly due to adverse effects. We did not find differences in efficacy and tolerability in people switched to doravirine-based ART with or without GRT. As expected, emergent NNRTI and NRTI resistance was common amongst those with virological failure on doravirine.

Dolutegravir (DTG), an integrase strand transfer inhibitor, is recommended as a first-line antiretroviral therapy (ART) for HIV/AIDS in international guidelines. In Japan, approved DTG-containing formulations include the single-agent DTG (Tivicay® tablets) and the fixed-dose combination of DTG, abacavir sulfate, and lamivudine (DTG/ABC/3TC, Triumeq® combination tablets). Although overseas clinical trials have demonstrated the favorable safety and effectiveness of these DTG-containing products, evidence specific to Japanese people living with HIV/AIDS (PLHIV) has remained limited. This report presents the final findings from a decade-long, prospective, post-marketing surveillance of single-agent DTG and DTG/ABC/3TC initiated in 2014. Data on the real-world clinical use of the single-agent DTG and DTG/ABC/3TC were obtained through the HIV-Related Drug Cooperative Survey, a national joint post-marketing program overseen by Japanese manufacturers of HIV therapies. Adverse drug reactions (ADRs) were captured and classified using the Medical Dictionary for Regulatory Activities. Associations between ADR incidence and potential risk factors were examined. Effectiveness was evaluated by longitudinal changes in plasma HIV RNA copy number and peripheral CD4+ cell counts. Among 2345 PLHIV included in the safety analysis, 652 patients (27.80%) reported ADRs. The most frequently reported ADRs were increased blood creatinine (4.78%), abnormal hepatic function (2.43%), and nausea (2.30%). ADR incidence was higher in participants with baseline comorbidities, those receiving concomitant medications, and ART-naïve participants, relative to their counterparts. Notably, no progressive increase in ADR incidence was observed during prolonged use > 2years. Plasma HIV RNA levels demonstrated sustained improvements from baseline in both ART-naïve and ART-experienced participants. By 12months after administration, the proportion of participants achieving plasma HIV RNA levels < 50 copies/ml was about 90% in ART-naïve participants and about 96% in ART-experienced participants. Additionally, CD4+ T cell counts also demonstrated sustained improvement from baseline in both ART-naïve and ART-experienced participants. This 10-year post-marketing surveillance confirms the long-term safety and effectiveness of single-agent DTG and DTG/ABC/3TC in Japanese PLHIV. No new safety concerns emerged over the 10-year surveillance period, further supporting their established safety profiles and reinforcing their continued role as key therapeutic options in routine clinical practice.

Prophylactic medications are commonly used to prevent tuberculosis and opportunistic infections in people living with HIV (PLWH) who are on first-line antiretroviral therapy (ART). However, their cumulative influence on cluster of differentiation 4 (CD4) responses is still a subject of ongoing investigation. A retrospective chart review was conducted utilizing secondary data derived from medical records of 500 people living with HIV (≥ 15 years) who initiated first-line ART at Jinka General Hospital in Ari Zone, South Ethiopia, between September 2019 and January 2025. CD4 response was defined as an increase of ≥ 50 cells/µL from baseline to the most recent measurement. The most recent CD4 measurement taken up to January 2025 was used for analysis. The primary outcome measure was a binary variable for CD4 response, defined as an increase of ≥ 50 cells/µL from baseline to end-line counts. Multivariable binary logistic regression was used to assess independent and interaction effects of prophylactic therapies on CD4 response. Among 500 participants, 50.2% demonstrated an improvement in CD4 count. Use of cotrimoxazole preventive therapy (CPT), isoniazid preventive therapy (IPT), and opportunistic infection (OI) medications was each independently associated with higher odds of CD4 improvement. However, interaction analysis showed that the CPT-OI combination and the triple CPT-IPT-OI regimen showed a statistically significant interaction suggesting a possible synergistic association with CD4 recovery beyond their individual additive effects. Predicted probabilities of CD4 improvement increased progressively with dual and triple prophylactic combinations compared with no prophylaxis. The combined use of prophylactic medications was significantly associated with CD4 recovery in people living with HIV on first-line ART. These findings emphasize the importance of integrated preventative strategies, particularly in resource-limited settings, and highlight the need for adherence support among individuals with limited formal education and those living in rural areas. The study's generalizability is limited, however, due to its single-center retrospective design and the use of a broad category for "OI prophylaxis" without specifying individual drugs.

The inability of antiretroviral medications to inhibit HIV is known as antiretroviral treatment failure. One of the greatest problems facing HIV patients receiving antiretroviral therapy is treatment failure. Updated data is crucial to assess program realities and effectiveness on ART. In this study, we aimed to determine incidence, survival, and risk factors for first-line ART failure by incorporating clinical, immunological, and virologic criteria, including primary health care. A retrospective cohort study was conducted among 579 adult patients. These patients were followed between January 1, 2016, and October 2023. Double-stage cluster sampling was used. The data were entered into Epi-Data version 3.1, then cleaned and analyzed via SPSS v.25. The Kaplan–Meier curve was used to estimate the probability of first-line ART failure. The log-rank test was used to compare the time to treatment failure. The Cox proportional hazard model was used to determine predictors of first-line ART failure. The overall incidence rate of first-line ART failure was 2.57/1000 person-months over 24,925.7 person-months of follow-up. The patients’ cumulative survival probabilities at 12 and 84 months were 100% and 76.73%, respectively. Predictor variables of first-line ART failure were male sex (AHR = 1.953; 95% CI: 1.11–3.43), disclosure of HIV infection (AHR = 0.53; 95% CI: 0.29–0.95), tuberculosis and HIV coinfections (AHR = 2.79; 95%CI: 1.33–5.87), opportunistic infections (AHR = 2.34; 95% CI: 1.23–4.28), poor/fair adherence (AHR = 3.87; 95% CI: 2.13–7.03), WHO clinical stage III/IV (AHR = 2.54; 95% CI: 1.04–6.20), and provision of CPT (AHR = 0.20; 95% CI: 0.08–0.51). The low incidence of first-line ART failure suggests effective ART implementation in the region. However, first-line ART failure was significantly linked to advanced WHO stage, poor adherence, TB/HIV coinfection, male sex, lack of cotrimoxazole prophylaxis, non-disclosure of HIV status, and opportunistic infections. These findings showed the need for early monitoring, adherence support, and comprehensive care. Not applicable.

Understanding how small molecules interact with DNA opens new avenues for designing smarter, more selective therapies. These studies not only shed light on off-target effects that could cause side effects or influence treatment outcomes but also help predict a drug’s genotoxic potential, aiding long-term safety assessments. Dolutegravir (DGV) serves as a second-generation integrase inhibitor used as a first-line antiretroviral therapy for managing human immunodeficiency virus (HIV) infection. Recent studies have positioned DGV as a prospective lead compound for repositioning antiretrovirals as cancer treatments. Building on this perspective, the introduced protocol presents a detailed approach to exploring DGV’s genomic interactions using salmon sperm DNA (SS-DNA) as a reliable genomic surrogate, employing various biophysical methods, including spectroscopic analysis, viscosity profiling, ionic strength experiments, and molecular docking. UV-Visible results indicate that DGV binds to DNA grooves with a binding constant of 103 M⁻¹, as determined by the modified Benesi–Hildebrand equation. Fluorescent displacement assays with ethidium bromide and rhodamine B confirm the groove interaction mode with SS-DNA. Potassium iodide quenching of DGV yielded comparable quenching constants of 24.99 and 23.61 M⁻¹ in the presence and absence of DNA, respectively, giving a confirmatory sign for groove binding interaction. A constant viscosity profile after the addition of DGV provides strong evidence of the groove binding mechanism, while ionic strength assays ruled out any significant electrostatic contribution. In silico molecular docking further shows DGV’s preference for GC-rich regions of SS-DNA. Thermodynamic measurements taken at various temperatures indicate that the interaction is spontaneous (∆G° = -15.0 to -25.4 kJ mol− 1) and primarily driven by hydrogen bonds and van der Waals forces (∆H° = -198.51 kJ mol− 1 and ∆S° = -573.33 J mol− 1 K− 1). Overall, this work provides a foundational framework and a pioneering step for future clinical and pharmacological research, as well as genome integrity assessments, with the ultimate goal of developing DNA-targeted drugs with higher selectivity and effectiveness.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-40136-y.

IntroductionSince July 2019, the WHO has recommended dolutegravir (DTG)-based regimens as preferred first-line antiretroviral therapy (ART) for adults and adolescents living with HIV (DTG-for-All), a reversal of a 2018 safety alert on use of DTG-based regimens by women of reproductive age (WRA). We examined sex and age disparities in DTG uptake before and after DTG-for-All in the International epidemiology Databases to Evaluate AIDS.MethodsWe included patients ≥16 years on or initiating treatment between January 2017 and July 2021 in 14 low- and middle-income countries where initial guidelines on DTG-based regimens for first-line ART either restricted use by WRA or had no such restrictions. We estimated the cumulative incidence of DTG uptake (CI-DTG) by sex and age group (aged 16–49 years vs 50+ years), stratified by patient, clinic and setting characteristics.ResultsAmong 177 706 patients on ART during the study period, 51% were females aged 16–49 years, with 25% males aged 16–49 and 13% and 11%, respectively, females and males aged 50+. At the time of DTG-for-All, overall CI-DTG was 29.6% (95% CI 29.4% to 29.8%); it was lower among females aged 16–49 (16.2%; 95% CI 16.0% to 16.5%) than males (41.1%; 95% CI 40.6% to 41.5%), with no sex disparities among patients aged 50+ (females: 46.0%; males: 47.0%). While DTG uptake subsequently increased among all groups, by July 2021, it remained substantially lower among females 16–49 (66.4%; 95% CI 66.1% to 66.7%), compared with males 16–49 and older females and males (75.8% to 77.5%). Concentrated in countries where initial guidelines on DTG restricted use by WRA, disparities in DTG uptake persisted at all health system levels and in both low-income and lower-middle-income countries.ConclusionsWhile sex-age differentials in DTG uptake narrowed after WHO’s DTG-for-All recommendation, lingering disparities in uptake underscore the difficulty of policy de-implementation when new evidence emerges.

Treatment failure of antiretroviral therapy (ART) has become an increasingly global health issue. In Ethiopia, prior studies on ART failure rates have focused primarily on adults in hospital settings with varying definitions of treatment failure, leaving pediatric data scarce. Thus, this study aimed to determine the incidence rate of treatment failure and its predictors among children enrolled in first-line ART in Jimma, Ethiopia. A retrospective cohort study was conducted at health facilities in Jimma, Ethiopia. A total of 312 children who were enrolled in first-line ART from January 2015 to December 2024 were selected via systematic random sampling. The data were retrieved by reviewing the child’s medical records and analyzed using Stata software. We utilized a multivariable Cox regression model to identify predictors of treatment failure and adjusted hazards ratio (AHR) with 95% confidence intervals (CI) to measure the associations. A p-value < 0.05 was used to declare statistically significant associations. The proportion of pediatric first-line ART failure in this study was 15.71% (95% CI: 11.57, 19.85), with an overall incidence density of 2.07 per 1,000 person-months (95% CI: 1.56, 2.74). The predictors significantly associated with ART failure were underweight (AHR = 3.95, 95% CI: 1.63, 9.57), anemia (AHR = 3.01, 95% CI: 1.51, 6.01), delayed ART initiation (AHR = 3.46, 95% CI: 1.32, 9.06), fair or poor adherence (AHR = 11.36, 95% CI: 5.22, 24.73), and advanced HIV disease (AHR = 2.49, 95% CI: 1.34, 4.66). Conversely, caregivers with positive serostatus (AHR = 0.191, 95% CI: 0.078, 0.46) and children aged 10–14 years (AHR = 0.064, 95% CI: 0.023, 0.17) had a significantly reduced risk of failure compared with their counterparts. First-line ART failure among children remains high, rendering achieving the nation’s HIV-free generation target difficult. To improve pediatric HIV outcomes in Ethiopia, future interventions should focus on rapid ART initiation, adherence counseling, nutritional support, and early anemia screening and management.

ODYSSEY trial showed superior efficacy of dolutegravir-based antiretroviral therapy (ART) versus then-current, non-dolutegravir standard of care over 96 weeks in children and adolescents living with HIV. The aim of this ancillary analysis was to compare anthropometric and body composition outcomes, including weight, height, BMI-for-age Z score, weight-for-age and height-for-age Z scores (<14 kg), mid-upper-arm circumference (MUAC), waist circumference, hip circumference, and body fat percentage, as well as metabolic outcomes (lipids and glucose), between dolutegravir and standard of care over approximately 5 years of follow-up. In this open-label, randomised, non-inferiority trial, children (aged ≥4 weeks and <18 years), weighing 3 kg or more, starting first-line ART (ODYSSEY-A) or switching to second-line ART (ODYSSEY-B) were enrolled in 29 centres in Germany, Portugal, South Africa, Spain, Thailand, Uganda, Zimbabwe, and the UK in two cohorts (children weighing ≥14 kg and children weighing <14 kg). Treatment effects (dolutegravir vs standard of care) were estimated on randomised allocation, accounting for treatment switches (substantial in standard of care arm during extended follow-up) through censoring and inverse-probability-of-censoring-weights. Changes in continuous outcomes were compared using linear mixed models, accounting for correlated slope and baseline value. Proportions of participants with unfavourable outcomes were compared using logistic mixed models. ODYSSEY is registered with ClinicalTrials.gov, NCT02259127, EUDRACT, 2014-002632-14, and ISRCTN, ISRCTN91737921. Between Sept 20, 2016, and Aug 26, 2019, 792 children were randomly assigned (392 to dolutegravir and 400 to standard of care). Of 707 children in the 14 kg or more cohort, 311 received first-line ART (ODYSSEY-A; 145 [92%] of 157 received efavirenz-based ART as standard of care) and 396 received second-line ART (ODYSSEY-B; 195 [98%] of 200 received boosted protease inhibitors as standard of care). Of 85 children in the less than 14 kg cohort, 72 received first-line ART (32 [74%] of 43 received lopinavir-ritonavir as first-line or second-line standard of care). Median follow-up on randomised allocation was 287 weeks (IQR 240-311) on dolutegravir-based ART and 205 weeks (168-240) on standard of care in the 14 kg or more cohort, and 220 weeks (208-232) on dolutegravir-based ART and 144 weeks (127-192) on standard of care in the less than 14 kg cohort. In the 14 kg or more cohort, 345 (49%) were female and 362 (51%) were male, 623 (88%) were Black African, median enrolment age was 12·2 years (IQR 9·1 to 14·9), weight 30·7 kg (23·4 to 43·0), and BMI-for-age Z score -0·6 (-1·4 to 0·1); 35 (5%) were overweight and six (1%) were obese. At week 240, adjusted mean differences (dolutegravir minus standard of care) were 1·0 kg for weight (95% CI -0·2 to 2·2; p=0·095) and 0·4 cm for MUAC (0·0 to 0·8; p=0·030), driven by differences in first-line participants, where higher increases were also observed in height, waist circumference, and hip circumference. Increases in BMI-for-age Z score, body fat percentage, and cross-sectional waist-to-height ratio were similar on dolutegravir-based ART and standard of care. Total cholesterol (-15·3 mg/dL [-21·0 to -9·5]; p<0·0001), triglycerides (-14·4 mg/dL [-25·2 to -3·6]; p=0·0089), and glucose (-4·4 mg/dL [-6·8 to -1·9]; p=0·0004) were lower with dolutegravir than standard of care. In the less than 14 kg cohort, 44 (52%) were female and 41 (48%) were male, 83 (98%) were Black African, median enrolment age was 1·4 years (IQR 0·6 to 2·0), weight 8·1 kg (5·4-10·0) and BMI-for-age Z score -0·8 (-1·9 to 0·2); three (4%) were overweight and none obese. Changes in weight, weight-for-age, BMI-for-age and height-for-age Z scores by 192 weeks were similar on dolutegravir and standard of care; there were small differences in MUAC (0·6 cm [-0·1 to 1·3]; p=0·070) and height (-2·5 cm [-4·5 to -0·5]; p=0·016). No significant differences in lipid biomarkers were observed; glucose decreased with standard of care but not with dolutegravir. Over approximately 5 years, indices defining excessive weight gain and central adiposity were similar with dolutegravir and other anchor drugs, and lipid and glycaemia profiles with dolutegravir were reassuring, providing supporting evidence for dolutegravir-based ART as the preferred treatment in children and adolescents. Fondazione Penta ETS, ViiV Healthcare, and UK Medical Research Council.

Few studies have compared body composition changes in children living with HIV receiving integrase inhibitors or boosted protease inhibitors. Children switching to second-line antiretroviral therapy were randomized to dolutegravir (DTG), darunavir/ritonavir (DRV/r), atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r), and to tenofovir alafenamide (TAF) or standard of care (abacavir or zidovudine) using a factorial design. Body composition was measured using bioelectric impedance analysis over 96 weeks. Associations between baseline characteristics and changes in fat mass, fat-free mass, muscle mass and body fat percentage were estimated using robust regression with multivariable fractional polynomial selection (exit P = 0.05). Eight hundred forty-one participants were included in the analysis. Females compared with males had greater fat accrual (+4.66% body fat, +1.32 kg fat mass; both P < 0.001). Compared with LPV/r, ATV/r and DTG exposures were associated with higher fat-free mass [+0.85 kg (95% confidence interval: 0.43-1.27) and +0.79 kg (0.37-1.21) respectively] and muscle mass [+0.82 kg (0.41-1.23) and +0.82 kg (0.42-1.22), respectively] (all P < 0.001). TAF and DRV/r exposures were associated with higher fat mass [+0.32 kg (0.12-0.52) P = 0.002; +0.33 kg (0.04-0.61) P = 0.025, respectively]. Prior nevirapine exposure was also associated with greater fat accrual [+0.36 kg (0.13-0.58) vs. efavirenz, P = 0.002]. Baseline CD4 and viral load, time on first-line antiretroviral therapy, and site were also associated with composition changes. DTG and ATV/r were associated with greater gains in fat-free mass and muscle mass than LPV/r, while DRV/r, TAF and prior nevirapine exposure were associated with fat mass accrual. Fat gain may initially reflect return to health but sustained increases may have metabolic implications. These findings suggest the need to monitor fat compartments with long-term exposure.

BackgroundHypertension is a major health concern in Sub-Saharan Africa (SSA). People living with human immunodeficiency virus (PLHIV) face unique risks for cardiometabolic disorders. However, the factors associated with hypertension among PLHIV have been understudied in SSA. This study examines the prevalence and determinants of hypertension among PLHIV in Ghana.MethodsA total of 440 PLHIV aged 18 years and older receiving antiretroviral therapy (ART) for a minimum of six months were recruited in this hospital-based cross-sectional study. Variables assessed included blood pressure, alcohol consumption, type of antiretroviral therapy (ART) medication, duration of exposure to ART, smoking history, age, sex, level of education, and exercise. Binary logistic regression was used to determine the factors associated with hypertension.ResultsThe overall prevalence of hypertension was 33%. People living with HIV who were on second-line ART had a lower risk of hypertension compared to those on first-line ART (OR = 0.379; 95% CI: 0.169–0.846; p = 0.018). Similarly, participants with high muscle mass (OR = 0.177; 95% CI: 0.064–0.487; p < 0.01) and those with very high muscle mass (OR = 0.220; 95% CI: 0.051–0.943; p = 0.041) had a lower risk of hypertension compared to those with low muscle mass. In contrast, participants who were obese had approximately four times greater odds of hypertension compared to those with underweight (OR = 4.046; 95% CI: 1.018–16.083; p = 0.047). Additionally, participants with medium IDDS (OR = 1.968; 95% CI: 1.150–3.369; p = 0.014) and high IDDS (OR = 2.348; 95% CI: 1.078–5.115; p = 0.032) had about twice the risk of hypertension compared to those with low IDDS.ConclusionThis study found a high prevalence of hypertension among PLHIV. Second-line ART may reduce the risk of hypertension, while higher muscle mass may have a protective effect. Further research is needed to better understand the impact of dietary diversity and specific dietary components on hypertension in this population.

Increasing evidence suggests that dolutegravir (DTG), endorsed by the WHO since 2018 for first-line antiretroviral therapy (ART), is associated with significant weight gain and potentially also with cardiometabolic disorders. In an effort to expand therapeutic options for people living with HIV (PLHIV), the EvaLuating the non-inferiority of DORAvirine vs DOlutegravir trial aims to compare the virologic efficacy of doravirine (DOR) and DTG-based regimens and to assess their safety, including a focus on cardiometabolic effects. This is an international, phase III, multicentre, open-label, non-inferiority, randomised trial that will enrol 610 ART-naïve PLHIV (HIV RNA≥1000 copies/mL at screening) across six countries (Brazil, Cameroon, France, Côte d'Ivoire, Mozambique and Thailand) spanning four continents. Key inclusion criteria include age ≥18 years, confirmed HIV-1 infection with plasma RNA levels ≥1000 copies/mL, indication for ART initiation and no prior ART exposure. Participants will be randomised in a 1:1 ratio to receive either DOR 100 mg once daily in combination with tenofovir disoproxil fumarate (TDF) (300 mg daily) plus lamivudine (3TC) (300 mg daily) or DTG (50 mg daily) in combination with TDF (300 mg once daily) plus either emtricitabine (FTC) (200 mg daily) or 3TC (300 mg daily). Randomisation will be stratified by screening HIV-1 RNA load (≤100 000 or >100 000 copies/mL) and by country. The primary outcome is virological efficacy, defined as the proportion of participants achieving HIV-1 RNA <50 copies/mL at week 48 on the assigned treatment (FDA Snapshot algorithm). Secondary outcomes include cardiometabolic safety endpoints (ie, weight gain, insulin resistance, hypertension, diabetes, waist and hip circumferences, waist-to-hip ratio, fasting glycaemia, insulin and fasting serum lipids), along with mental health, quality of life, virological and immunological parameters. Final data collection is expected by July 2028. Primary outcome results (week 48) are expected in early 2028. The project was submitted to and approved by national ethics committees and pharmaceutical regulatory authorities in all participating countries: Brazil (CEP INI FIOCRUZ (21.040-900)/CEP HGNI (26.030-380)); Cameroon (CNERSH (2024/09/1717/CE/CNERSH/SP)/Ministry of Public Health (D30-1464/AAR/MINSANTE/SG/DROS/CRC); Côte d'Ivoire: (CNESVS (0018224/MSHPCMU/CNESVS-km)/AIRP (1329/AIRP/DISMP/Om/kbaag); France (CTIS CPP/ANSM (2023-508626-10-00)); Mozambique (CNBS (20/CNBS/25)/ANARME (4635/380/ANARME)); Thailand: (IHRP (08/1944)/Thai FDA: ongoing on 19 January 2026). The trial received authorisation from the French National Commission for Data Protection and Liberties (CNIL) under approval number 924 302. Written informed consent is obtained from all participants prior to any study-specific procedures and trial enrolment, in accordance with the Declaration of Helsinki and applicable national regulations. Study findings will be disseminated through publication in peer-reviewed journals and presentations at national and international scientific conferences. Results will also be communicated to policymakers, healthcare professionals, community stakeholders and study participants through appropriate dissemination activities, including policy briefs, stakeholder meetings and lay summaries on dedicated and easily accessible platforms. NCT06203132; EU-CT, 2023-508626-10-00.

Introduction of pediatric-friendly dolutegravir (DTG) formulations to treat children living with HIV (CLHIV) has presented new opportunities to improve viral suppression; however, there are limited data on emerging patterns of HIV drug resistance (HIVDR) in this population. We identified CLHIV aged 0-15 years experiencing virologic failure on first-line antiretroviral therapy in Uganda between January 2021 and November 2021 from the Central Public Health Laboratory database. Remnant viral load samples were tested for HIVDR using Sanger sequencing. Drug resistance mutations (DRMs) were identified, and antiretroviral susceptibility was interpreted using the Stanford University HIVDR Database algorithms. The prevalence of DRMs and HIVDR is summarized using descriptive statistics, and associations with demographic and clinical factors were determined using χ 2 tests. Among 333 successfully genotyped patient samples, 122 (36.6%) CLHIV were on a DTG-based regimen and 136 (40.8%) on a lopinavir-based regimen. Among all CLHIV, 271 (81.4%) had DRMs and 262 (78.7%) had any intermediate-to-high level HIVDR [including DTG (1.8%), lopinavir (9.6%), abacavir (ABC) (25.5%), and zidovudine (19.2%)]. Among CLHIV on a DTG-based regimen, 6.6% had any integrase inhibitor DRMs and 4.1% had intermediate-to-high resistance to DTG. Children on DTG-based regimens were less likely to have DRMs ( P = 0.007) or HIVDR ( P = 0.02) compared with all other regimens. CLHIV on DTG-based regimens with an ABC backbone were no more likely to have DRMs ( P = 0.9) or HIVDR ( P = 0.5) compared with those with a backbone not containing ABC. Low rates of DTG resistance among Ugandan CLHIV failing first-line DTG-based antiretroviral therapy regimens underscore the durability of DTG. Lack of difference in ABC resistance across all regimens supports maintaining an ABC backbone for CLHIV <30 kg when transitioning to a DTG-based regimen despite virologic failure.

BackgroundVirologic failure in children is a significant public health concern in sub-Saharan Africa. This study aims to assess the incidence rate of virologic failure and its predictors among children undergoing first-line antiretroviral therapy (ART) in Ethiopia.MethodsA multicenter retrospective follow-up study was conducted in HIV-infected children on first-line ART from January 1, 2013, to December 31, 2022, in Ethiopia. A simple random sampling method was employed to select the sample. Data entry was performed using EpiData, and analysis was conducted using STATA version 14. Kaplan-Meier curves and log-rank tests were utilized for survival analysis.ResultAmong 537 HIV-infected children followed over the study period, 12.29% developed virologic failure, yielding an incidence rate of 17 per 10 000 person-month observations (95% confidence interval [CI]: 13.4, 21.7). Factors independently associated with an increased risk of virologic failure included poor ART adherence (adjusted hazard ratio [AHR] = 2.63; 95% CI: 1.38, 4.97), advanced World Health Organization (WHO) Treatment (T) stages III and IV (AHR = 2.71; 95% CI: 1.15, 6.37), no history of regimen change (AHR = 5.88; 95% CI: 3.23, 10.71), and age at ART initiation above 10 years (AHR = 2.97; 95% CI: 1.30, 6.78). In contrast, having a caregiver younger than 40 years was associated with a significantly lower risk of virologic failure (AHR = 0.42; 95% CI: 0.25, 0.72). These findings emphasize the importance of monitoring adherence, providing closer follow-up for children in advanced treatment stages, and considering caregiver-related factors to reduce virologic failure.ConclusionsVirologic failure among HIV-infected children on first-line ART in Northwest Ethiopia was a relatively low incidence. Interventions targeting poor adherence, children with advanced WHO Treatment (T) stage, older age at ART initiation, and those with no history of regimen change are essential. Additionally, caregiver characteristics, such as age below 40 years, play a protective role and should be considered when designing adherence support and monitoring strategies to further reduce the risk of virologic failure.

Our study assesses human immunodeficiency virus (HIV) drug resistance (HIVDR) in patients failing first-line (1L) antiretroviral therapy (ART) with dual nucleoside analog reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens in India. In this cross-sectional study, consecutive HIV-1-infected patients aged 13 years or older, failing 1L ART after at least 12 months exposure, underwent HIV genotyping and drug resistance testing (DRT) using the ViroSeq™ HIV-1 Genotyping System and the Stanford HIV-1 Database, with HIVDR classification based on a penalty score of ≥30. Among 115 eligible participants, 110 underwent DRT, revealing efavirenz (EFV) or nevirapine (NVP) resistance rates of 85.3% (n = 93/109) and 87.2% (n = 95/109), respectively, and substantial cross-resistance to rilpivirine (RPV) (37.6%, n = 41/109), etravirine (ETV) (30.3%, n = 33/109), and doravirine (DOR) (60.5%, n = 66/109). The cohort was categorized into 3 groups based on their previous ARV drug exposure: group A (36.4%, n = 40) with prior TA exposure (AZT or d4T) but no TFV exposure; group B (19.1%, n = 21) with prior nonconcomitant exposure to both TAs and TFV; and group C (44.5%, n = 49), exposed to TFV only. Despite group B's 1L ART regimen failure with TFV, the prevalence of AZT resistance was similar (difference in proportions, ∇P: 14.6%, p = 0.277) between group A [57.5% (n = 23/40)] and group B [42.9% (n = 9/21)]. TFV resistance was comparable (∇P: 0.8%, p = 0.947) between group A (32.5%, n = 13/40) and group B (33.3%, n = 7/21), despite group A's lack of TFV exposure, and was also similar to the TFV-only-exposed group (group C: 38.8%, n = 19/49). Regarding distinct DRM patterns, the prevalence of K65R DRM was higher (∇P: 22.4%, p = 0.060) among TFV-only-exposed patients (group C: 36.7%, n = 18/49) compared with PLH exposed to both TAs and TFV (group B: 14.3%, n = 3/21), whereas multiple TAMs occurred at similar rates (∇P: 12.1%, p = 0.367) among TA-exposed patients [group A: 55.0% (n = 22/40) vs group B: 42.9% (n = 9/21)]. The research provides insights into the complexities of HIVDR, emphasizing the interplay of resistance patterns and the role of drug exposure history, especially in the context of resistance to TFV and second-generation NNRTIs. Ensuring adequate drug exposure history in patients can prevent poor outcomes in PLH being treated with ART due to resistance. Resistance profiling is especially relevant following first-line ART failure.

Most first-line antiretroviral therapy (ART) regimes in Sub-Saharan Africa contain tenofovir disoproxil fumarate (TDF) which has a nephrotoxic potential. Baseline renal function assessment is not feasible in many settings and therefore not required prior to starting ART according to Malawian guidelines. We assessed renal function over 36 months in people living with HIV (PLHIV) starting TDF-based ART at Lighthouse Clinic, Lilongwe, Malawi. Data on demographics, medical history, laboratory values, WHO stage, and anthropometric measures were collected at study entry and during visits at 1, 3, 6 months, and every 6 months until month 36. The main outcome of the study was renal function, defined by the estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI equation. Descriptive statistics and multivariable linear regression analysis were performed. A baseline creatinine value was available for 1,430 PLHIV (57% female, mean age ± SD 36.0 ± 9.3 years). Of these, 443 PLHIV (62% female) were observed until month 36. Factors associated with changes in eGFR over time included baseline log-transformed eGFR (coefficient = −0.787; p < 0.001), MAP at baseline, and initial WHO clinical HIV stage. The overall trend in eGFR categories indicated a shift towards lower classes. In this large cohort of PLHIV, TDF did not result in a decline in eGFR. Indeed, an unexpected trend of improved renal function was observed. Even though findings need to be interpreted with caution due to considerable attrition, our results suggest TDF can be administered safely in resource-limited settings where ART decisions are frequently made without pre-treatment renal assessment.

Dolutegravir/lamivudine (DTG/3TC), used as a two-drug regimen (2DR), has demonstrated non-inferiority to traditional three-drug regimens (3DRs) in treatment-naive people with HIV (PWH), with sustained virological efficacy, favorable tolerability, and a good safety profile. However, its implementation in routine clinical practice raises several questions, particularly in populations underrepresented in registration trials. This review critically appraises current evidence supporting DTG/3TC as first-line antiretroviral therapy, drawing from randomized clinical trials and real-world studies. Available data indicate that DTG/3TC maintains high virological suppression rates even in individuals with high baseline viral load (&amp;gt;500,000 copies/mL), with no emergent resistance. Evidence from test-and-treat settings suggests comparable efficacy to triple therapy, provided that hepatitis B coinfection and transmitted resistance are adequately excluded. Preliminary data in late presenters and those with advanced disease support its effectiveness, although confirmatory trials are warranted. Beyond viro-immunological outcomes, DTG/3TC appears equivalent to triple regimens in reducing viral reservoirs, immune activation, and systemic inflammation. Evidence in women living with HIV, including during pregnancy, remains limited but reassuring, with no major safety concerns identified. Overall, the body of clinical and real-world evidence supports DTG/3TC as a simplified and durable first-line regimen for most treatment-naive PWH. Ongoing research should further define its role in acute infection, advanced HIV disease, and specific subpopulations such as women and individuals from regions with high prevalence of non-B subtypes.

BackgroundPediatric human immunodeficiency virus (HIV) remains a significant public health challenge, with an estimated 1.5 million children living with HIV globally. In addition, first-line antiretroviral therapy (ART) treatment failure has remained high, as studies and reports showed. Furthermore, time to treatment failure and its predictors on first-line ART among HIV-infected children are less researched in the study area after the test-and-treat strategy is implemented. Hence, this study was conducted to assess time to treatment failure and its predictors among children receiving first-line antiretroviral therapy in Tigray Region public general hospitals, North Ethiopia, 2024.MethodsA hospital-based retrospective cohort study was conducted among children who started ART from January 2014 to March 2020 and from February 2023 to August 2023 in Tigray Region public general hospitals. Epi Data version 3.1 and Stata version 14 were used for data entry and analysis, respectively. Kaplan-Meier and log-rank tests were computed. Bivariable analysis variables with p-value < 0.2 were taken to multivariable Cox regression analysis to identify predictors. Finally, 95% CI and p-value <0.05 were considered for statistical significance.ResultsFrom 410 records of children, 55 (13.4%) (95% CI, 10.43–17.08) had treatment failure, with an incidence rate of 3.3 (95% CI, 2.6–4.3) per 1000 child-month observation. The median time to treatment failure was greater than or equal to 75 months. Poor adherence (AHR = 3.6, 95% CI: 1.7–7.5), baseline CD4 count <200 cells/mm3 (AHR = 3.8, 95% CI: 1.8–8.4), baseline CD4 count 201–350 cells/mm3 (AHR = 2.7, 95% CI: 1.2–6.2), and initial Nevirapine-based regimen (AHR = 4, 95% CI: 1.8–8.8) were predictors of time to treatment failure.Conclusion and recommendationThe incidence of treatment failure among children receiving first-line ART was found to be high according to the UNAIDS virological suppression targets. Poor adherence, baseline CD4 count, and initial NVP-based regimen were predictors of time to treatment failure of ART. Hence, all children on ART should be closely monitored, mainly on these identified predictors.