First-line Antiretroviral Therapy Research Articles

Population pharmacokinetic modeling of paired plasma-breast milk lamivudine data for estimation of infant exposure in breastfeeding mother-infant pairs.

Around 1.2 million women living with HIV give birth annually, majority of whom will breastfeed their infants while receiving antiretroviral therapy (ART). Lamivudine, a component of first-line ART regimens crosses from maternal plasma to breast milk, with measurable concentrations in some breastfed infants. Wide variability in plasma-to-breast milk transfer has been reported within- or across studies, probably due to differences in sampling framework. This work sought to characterize the milk-to-plasma transfer of lamivudine, quantify inter-patient variability and associated factors, and predict exposure of a breastfed infant. We explored data from an observational pharmacokinetic study that included 35 Ugandan mothers and their infants. Mothers received lamivudine doses of 150 mg twice daily or 300 mg once daily as part of their antiretroviral regimen. Pharmacokinetic sampling was undertaken across two visits approximately 8 weeks apart, providing 248 maternal plasma, 256 breast milk-, and 151 infant blood concentrations, measured across a 24-h sampling interval. A one-compartmental model best described the plasma disposition of lamivudine, with first-order absorption, interindividual variability on clearance and volume of distribution, and a proportional residual error model. A lag in time of plasma-to-breast milk drug accumulation was described using an effect compartment model with a milk-to-plasma ratio of 1.77. An estimated daily infant dose of 179.3 μg/kg (range: 125.8, 282.3) closely predicted the observed infant steady-state concentrations and translated into 3.34% (2.13, 7.20) and 3.35% (1.10, 7.15) of the standard daily maternal dose in visits 1 and 2, respectively. The established modeling framework can be extended to other drugs.

Global, regional, and national prevalence of HIV-1 drug resistance in treatment-naive and treatment-experienced children and adolescents: a systematic review and meta-analysis

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. 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. 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. 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. 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).

All Blood Brain Barrier Cell Types Demonstrate Capability to Influence Differential Tenofovir and Emtricitabine Metabolism and Transport in the Brain.

The blood brain barrier (BBB) represents a significant obstacle in brain drug penetration that challenges efforts in the treatment of neurological disorders. Therapeutically targeting the brain requires interactions with each BBB cell type, including endothelial cells, pericytes, and astrocytes. Yet, the relative contribution of these BBB cell types to the mechanisms that facilitate brain drug disposition is not well characterized. Here, we use first-line antiretroviral therapies, tenofovir (TFV) and emtricitabine (FTC), as models to investigate the mechanisms of drug transport and metabolism at the BBB that may influence access of the drug to the brain. We evaluated regional and cell-type-specific drug metabolism and transport mechanisms using rhesus macaques and in vitro treatment of primary human cells. We report heterogeneous distribution of TFV, FTC, and their active metabolites, which cerebrospinal fluid measures could not reflect. We found that all BBB cell types possessed functional drug-metabolizing enzymes and transporters that promoted TFV and FTC uptake and pharmacologic activation. Pericytes and astrocytes emerged as pharmacologically dynamic cells that rival hepatocytes and were uniquely susceptible to modulation by disease and treatment. Together, our findings demonstrate the importance of considering the BBB as a unique pharmacologic entity rather than viewing it as an extension of the liver, as each cell type possesses distinct drug metabolism and transport capacities that contribute to differential brain drug disposition. Further, our work highlights pharmacologically active pathways at the BBB that may regulate brain drug disposition and impact therapeutic efforts to alleviate neurologic disease.

Prevalence, rate, and predictors of virologic failure among adult HIV-Infected clients on second-line antiretroviral therapy (ART) in Tanzania (2018–2020): a retrospective cohort study

BackgroundAntiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania.ResultsWe followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count < 200 cells/mm3 during second-line ART (HR 1.89 (95% CI 1.46, 2.44), and being on ART for 13–35 months (HR 8.22 (95% CI 2.21, 30.61). Paradoxically, having a CD4 count < 200 cells/mm3 during first-line ART treatment was associated with a reduced risk of virologic failure (HR 0.77 (95% CI 0.60, 0.99).ConclusionsIn Tanzania, approximately 30% of adult clients on second-line ART experience VF at a rate of 92.71 per 1000 person-years. This high virologic failure rate underscores the urgent need for targeted interventions, such as enhancing adherence support, optimizing drug regimens, and regular viral load monitoring. These interventions will reduce the need for switching to the more costly and toxic third-line ART therapy and are also crucial for achieving the UNAIDS goal of 95% viral suppression among treated individuals by 2030.

Association of first-line combination antiretroviral therapy with malaria among adult HIV-infected persons in Jos, Nigeria: a pilot cross sectional study

BackgroundMalaria and human immunodeficiency virus (HIV) infection coexist in significant numbers in some geographic areas including sub-Sahara Africa (SSA). HIV-infected patients are a World Health Organization (WHO) recognized high risk group for increased malaria morbidity. Majority of HIV-infected patients undertaking treatment in SSA are on WHO recognized first-line combination antiretroviral therapy (cART). Considering the immunity-enhancing capacity of antiretroviral therapies on people living with HIV, this study aimed to explore the association between first-line combination antiretroviral therapy (cART) with malaria parasitaemia and antigenaemia in adult HIV-infected persons and to determine the predictors of malaria antigenaemia in adult persons living with HIV.MethodsThe study was conducted at the AIDS Prevention Initiative in Nigeria (APIN) Centre, Jos University Teaching Hospital, Jos, Plateau State, from August 2018 to February 2019. Epi Info statistical tool was used to determine the sample size and power of the study. The study population consisted of three groups. The first group comprised first-line cART-experienced adult HIV-seropositive subjects, the second group comprised ARV-naïve HIV-seropositive adults and the third group comprised HIV-seronegative adults. For this pilot study, 60 persons were recruited into each group via convenience sampling. Malaria rapid diagnostic test (RDT) was performed according to manufacturer’s instruction for all the study participants using SD Bioline Malaria Ag P.f (HRP2/pLDH) (Standard Diagnostics, Hagal-Dong, Korea). All the study participants also had thick and thin blood film malaria microscopy. Data collected was processed and analyzed using the Stata statistical software version 15 (StataCorp, College Station, Texas). Chi square was used to test the association between malaria and first-line cART exposure. Univariate and multivariate analysis were also done to identify factors that were independently associated with malaria antigenaemia.ResultsA total of 180 persons participated in the study and involved 60 participants recruited in each of the three study groups. Overall, the predominant study participants were females (56.67%), traders (27.78%), secondary school leavers (43.33%) and urban dwellers (88.89%). Their mean age and standard deviation was 37.07 ± 11.53 years. Using malaria microscopy, the prevalence of malaria parasitaemia in ARV-naïve HIV-infected persons was 5% and 0% in the first-line cART-experienced HIV-infected persons as well as the HIV-negative persons. Malaria RDT result was positive in 7/60 (11.67%) of the first-line cART experienced HIV-infected participants, 6/60 (10%) of the ARV-naïve HIV-infected group and 1/60 (1.67%) of the HIV-negative group. Of the seven positive malaria RDT results in those on first-line cART, five persons were receiving zidovudine/lamivudine/nevirapine (AZT/3TC/NVP) while the remaining two were receiving tenofovir disoproxil fumarate/lamivudine/efavirenz (TDF/3TC/EFV), thus making an antigenaemia proportion of 16.67% and 6.67% respectively. Being an HIV-infected person on first-line cART (OR = 16.20, p = 0.04), having a headache (OR = 6.21, p = 0.03) and non-usage of window nets (OR = 3.74, p = 0.05) were found to be predictors of malaria antigenaemia.ConclusionMalaria parasite burden in HIV-infected persons on first-line cART is lower than that observed in ARV-naïve HIV-infected persons. Our study suggests that TDF/3TC/EFV may be associated with lower malaria antigenaemia when compared with AZT/3TC/NVP and can be considered an alternative first-line antiretroviral regimen in malaria-endemic regions.

Empowering adolescents living with perinatally-acquired HIV: tailored CD4+ count assessment for optimized care, the EDCTP READY-study.

The elevated rate of AIDS-related mortality in Sub-Saharan Africa among adolescents living with HIV (ALHIV) is influenced by various factors, notably immunosuppression, within a framework of limited therapeutic alternatives. We aimed to enhance the management of pediatric HIV by assessing the immune response and associated factors in perinatally-infected ALHIV on antiretroviral therapy (ART) in Cameroon. A cohort study was conducted from 2018-2020 among 271 ART-experienced ALHIV in Cameroon. Sociodemographic data, immunological (CD4), and virological (plasma viral load, PVL) responses were measured at enrolment (T0), 6-months (T1), and 12-months (T2) using PIMA CD4 (Abbott/Pantech (Pty) Ltd) and Abbott Applied Biosystem platform (Real-Time PCR m2000RT) respectively. Immunological failure (IF) was defined as absolute CD4 < 250 cells/mm3, and Virological failure (VF) as PVL ≥ 1,000 copies/ml. A linear mixed-effects model with R version 4.4.1 was used to estimate both fixed and random effects, with significance set at p < 0.05. Of the 271 perinatally-infected ALHIV enrolled over three phases, females were predominant (55.7, 55.1, and 56.0%); median age was 14 (IQR: 12-17); majority of the participants were followed-up in urban areas (77.5, 74.5, and 78.6%); and the age distribution favored older adolescents (48.7, 61.2, and 58.5%). Most participants achieved clinical success (93.1, 89.7, 88.9%), predominantly on first-line ART (80.8, 66.2, and 53.0%), with good adherence (64.2, 58.9, and 64.5%). Most participants had secondary education (67.2, 70.1, and 67.5%). Median CD4+ counts fluctuated overtime, with values of 563 (IQR: 249.0-845.0), 502 (IQR: 319.0-783.5), and 628 (IQR: 427.5-817.5), respectively. Of note, being male was linked to a reduction in CD4+ count compared to females, [-200.63 (-379.32 to -21.95), p = 0.028]. Similarly, late adolescence was associated with lower CD4+ counts compared to early adolescence, [-181.08 (-301.08 to -61.09), p = 0.003]. Moreover, participants experiencing VF showed significantly lower CD4+ counts compared to those with undetectable viral loads, [-353.08 (-465.81 to -240.36), p < 0.001]. Additionally, there was a marginally significant interaction between male gender and secondary educational level, [209.78 (-6.94-426.51), p = 0.058]. Among perinatally-infected ALHIV, age, gender, educational level, and virological status are key factors influencing their immune health and treatment outcomes. Prioritizing targeted interventions and close monitoring within these subgroups is crucial for optimal management, employing holistic care strategies that consider not only medical interventions but also psychosocial support and education.

Rapid and sensitive liquid chromatographic–tandem mass spectrometric methods for the quantitation of dolutegravir in human plasma and breast milk

BackgroundDolutegravir (DTG) is part of a first-line antiretroviral therapy (ART) for HIV management in drug-naïve individuals and is recommended for the treatment of HIV during pregnancy. Robust analytical tools to quantify DTG are necessary to support clinical trials that characterize its multi-compartment drug distribution. MethodsPotassium EDTA (K2EDTA) plasma or whole breast milk was spiked with DTG and an isotopically labeled internal standard. Samples were prepared via protein precipitation prior to LC–MS/MS analysis. The assays were validated in accordance with regulatory recommendations. ResultsAnalytical measuring ranges for DTG quantitation in plasma and breast milk were 100–10,000 ng/mL and 0.500 to 1000 ng/mL, respectively. Inter-assay precision and accuracy were 2.73 % to 3.41 % and −10.6 % to −5.37 % for plasma, and 4.24 % to 12.4 % and −5.63 % to 7.49 % for breast milk, respectively. DTG was stable for three freeze–thaw cycles and for at least 72 h at room temperature in matrix (plasma or breast milk). Additionally, whole blood was stable for 24 h at room temperature and 2 h under conditions of extended heat and humidity. Matrix effects for DTG in plasma and breast milk ranged from 101 % to 108 % and 78.2 % to 99.3 %, respectively. Quantitation in remnant plasma samples yielded measurable concentrations within the primary linearity of the assay. ConclusionsMethods to quantify DTG in human plasma and breast milk have been developed and validated. These assays were designed to satisfy all criteria for implementation in clinical and clinical trial settings.

DORA: 48-week weight and metabolic changes in Black women with HIV, in a phase IIIb switch study from dolutegravir- or efavirenz- to doravirine-based first-line antiretroviral therapy.

Treatment-related weight gain and metabolic complications with antiretroviral integrase-based regimens, especially among Black women, suggest the need for alternative options. We conducted a 48-week, open-label, single-arm, single-centre, phase IIIb switch study to evaluate the tolerability, safety and efficacy of switching from stable efavirenz- or dolutegravir-based antiretroviral therapy to doravirine/lamivudine/tenofovir disoproxil fumarate in Black women. The 101 participants enrolled (median age 35 years; interquartile range 31-40) were on efavirenz (n = 46; mean duration on therapy 1.7 years) or dolutegravir-based (n = 55; mean duration 1.5 years) antiretrovirals at screening. Retention at 48 weeks was 92/101 participants, and viral suppression was >90% throughout the study, with a single case of doravirine resistance (106 M, V108I and H221Y mutations). The mean weight percentage change at week 48 was 4.7% (95% confidence interval [CI] 3.0-6.5; p < 0.001), and the adjusted mean change was 2.7 kg (95% CI 1.50-3.98; p < 0.001); for efavirenz, the percentage change was 5.0% (95% CI 2.9-7.1; p < 0.001), and the adjusted weight gain was 3.5 kg (95% CI 1.93-5.13); for dolutegravir, the percentage change was 4.5% (95% CI 1.8-7.3; p < 0.001), and the adjusted weight gain was 2.1 kg (95% CI 0.26-3.90). Statistically significant decreases in lipid panel percent mean to week 48 included: total cholesterol -8.4% (95% CI -11.3 to -5.5; p < 0.001), triglycerides -10.4% (95% CI -16.4 to -4.4; p < 0.001) and high-density lipoprotein -14.8% (95% CI -18.5 to -11.2%; p < 0.001), with minor differences when disaggregating the mean percent change in lipids between previous efavirenz/dolutegravir regimens. Adverse events due to doravirine were few and mild. Our findings suggest that a switch to doravirine from efavirenz or dolutegravir is safe and effective in Black women, with significant improvement in lipid profiles, but does not arrest progressive weight gain.

HIV-1 residual risk and pre-treatment drug resistance among blood donors: A sentinel surveillance from Gabon.

Surveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon. A sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance. Five HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02_AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02_AG, P = 0.3 and Recombinants, P = 0.5). This sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors.

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

Identification and simultaneous quantification of potential genotoxic impurities in first-line HIV drug dolutegravir sodium using fast ultrasonication-assisted extraction method coupled with GC–MS and in-silico toxicity assessment

Dolutegravir (DLG) has become a distinctive first-line antiretroviral therapy for the treatment of HIV in most countries due to its affordability, high efficacy, and low drug-drug interactions. However, the evaluation of genotoxic impurities (GTIs) in DLG and their toxicity assessment has not been explored thoroughly. Thus, in this study, a simple, fast, and selective analytical methodology was developed for the identification and determination of 7 GTIs in the comprehensive, explicit route of synthesis for the dolutegravir sodium (DLG-Na) drug. A facile, fast ultrasonication-assisted liquid–liquid extraction procedure was adapted to isolate the GTIs in DLG-Na and then analyzed using the gas chromatography (GC)-electron impact (EI)/mass spectrometer (MS) quantification (using selective ion monitoring mode) technique. This EI-GC/MS method was validated as per the current requirements of ICH Q2 (R1) guidelines. Under optimal method conditions, excellent linearities were achieved with R between 0.9959 and 0.9995, and high sensitivity was obtained in terms of detection limits (LOD) between 0.15 to 0.63 µg/g, and quantification limits (LOQ) between 0.45 to 1.66 µg/g for the seven GTIs in DLG. The obtained recoveries ranged from 98.2 to 104.3 % at LOQ, 15 µg/g, and 18 µg/g concentration levels (maximum daily dose of 100 mg). This developed and validated method is rapid, easy to adopt, specific, sensitive, and accurate in estimating the seven GTIs in a relatively complex sodium matrix of the DLG-Na drug moiety. As a method application, two different manufactured samples of DLG-Na drug substances were analyzed for the fate of the GTIs and drug safety for the intended dosage applications. Moreover, an in-silico QSAR toxicity prediction assessment was carried out to prove scientifically the potential GTI nature of each impurity from the alerting functional groups.

Optimizing HIV care: Insights from CD4 count, viral load, and demographic factors in a tertiary care centre of South Gujarat

PurposeDespite advancements in prevention, diagnosis, and treatment, HIV/AIDS remains a critical health concern, particularly in India. This study contributes valuable insights into HIV management strategies. This prospective and retrospective longitudinal observational study aimed to analyze the trends in CD4 cell count and viral load suppression among adult People Living with HIV (PLHIV) undergoing antiretroviral therapy (ART) and evaluate the influence of demographic factors and ART adherence on these parameters at the ART Centre of New Civil Hospital, Surat, India. Materials & methodsAdult PLHIV registered and initiated on ART between June 2017 and May 2018 at ART-NCH, Surat with Continuous follow-up until 2023 were included in the study. Data was collected and Statistical analysis was performed using Microsoft Excel and SPSS software. Other factors were evaluated for their influence on treatment outcomes. ResultsA longitudinally analyzed data from 365 adult PLHIV receiving ART with continuous follow-up until 2023 revealed significant trends, with CD4 counts increasing from 425 (1st month) to 612.67 (24th month), indicating improving immune function. Individuals on first-line ART regimens had significantly higher odds (OR: 3.5, 95 % CI: 1.1–11.3) of achieving CD4 counts ≥350 compared to those on second-line regimens. Adherence to treatment (OR: 1.98, 95 % CI: 1.1–3.4) also increased the odds of attaining CD4 counts ≥350. Viral load suppression was achieved in 353 out of 365 participants. ConclusionThis study highlights the need for tailored interventions to optimize immune recovery and viral load suppression among PLHIV. Recommendations include targeted intervention to improve long-term health outcomes.

Retinal Vessel Functional Responses in South Africans Living With and Without HIV: The EndoAfrica-NWU Study.

The effects of HIV and antiretroviral therapy (ART) on microvascular function are poorly explored. We compared retinal vessel functional responses to flicker light-induced provocation (FLIP) in people living with HIV (PLWH) and people living without HIV (PLWoutH). We included 115 PLWH and 51 PLWoutH with a median age of 41 years. Treated PLWH received similar first-line fixed-dose combination ART. Clinical characteristics and retinal vessels functional responses to FLIP were compared in (a) PLWH and PLWoutH; and (b) PLWH groups stratified by the median of (i) CD4-count (511 cells/mm3), (ii) viral load (50 copies/mL), and (iii) ART duration (57.6 months). PLWH were older, smoked more, and had a lower prevalence of hypertension than PLWoutH (p < 0.05). Almost 64% of PLWH were infected for more than 5 years. Retinal vessel responses to FLIP were similar between PLWH and PLWoutH after taking confounders into account. In addition, PLWH subgroups stratified according to immuno-virological status by CD4-count, viral load, and ART duration showed no differences in retinal vessel responses to FLIP. Living with HIV and receiving ART were not associated with altered microvascular function as assessed with dynamic retinal vessel analysis in a South African case-control study.

Determinants of High HIV Infection Prevalence in Vijayapura, Bagalkot, and Belagavi Districts in Karnataka, India.

Introduction India has the second-highest number ofpeople living withhuman immunodeficiency virus (PLHIV). Despite the national decline in the prevalence of the human immunodeficiency virus (HIV) from 2000 to 2021, regional variations persist, particularly in the northeastern and southern states. High-risk populations, including female sex workers (FSW), men who have sex with men (MSM), and injecting drug users (IDU), significantly contribute to these dynamics. This study focuses on high-prevalence districts in Karnataka. Objectives This study aims to identify socioeconomic and behavioral factors associated with high HIV prevalence in high-burden districts of South Indian states. Methodology A cross-sectional study was conducted using data from Integrated Counseling and Testing Centers (ICTCs) and Designated STI/RTI (sexually transmitted infections/reproductive tract infections) Clinics (DSRCs) across 24 centers in the three districts. The centers were determined using a simple random sampling method. Data from 2501 HIV-positive individuals were analyzed, focusing on demographics, risk behaviors, and treatment history. Results Males constituted the majority of HIV cases, accounting for 448 (56.0%) in Vijayapura, 334 (51.4%) in Bagalkot, and 644 (61.1%) in Belagavi districts, with a significant portion referred by government hospitals. High HIV prevalence was linked to adults aged 25-49 years of age; the number of people with HIV was high among daily wage workersand individuals with multiple sexual partners compared to married and educated people. Newly diagnosed discordant couples ranged from 129 (12.2%) in Belagavito 133 (18.4%) in Vijayapuradistricts. Most patients were on first-line antiretroviral therapy (ART), with loss to follow-up attributed to system negligence and poor compliance. Conclusion Key determinants of high HIV prevalence include gender, age, marital status, socioeconomic status, and sexual behavior. Effective interventions require targeted education, improved healthcare services, robust surveillance, and strengthened collaboration among stakeholders.

Brief communication: The rate of switching from first-line to second-line antiretroviral therapy among people living with HIV in Aden City, Yemen

BackgroundEffective management of antiretroviral therapy (ART) is crucial in combating the global HIV pandemic. This study, the first of its kind in Yemen, investigates the rate and determinants of switching from first-line to second-line ART among people living with HIV (PLWH) in Aden City, Yemen.MethodsA retrospective cohort study was conducted using data from PLWH who started first-line ART at Al-Wahda Hospital from 2007 to May 2022. PLWH in prevention of mother-to-child transmission (PMTCT) programs, those already on second-line ART at enrollment, and those with less than 3 months of follow-up were excluded. Cumulative incidence curves and multivariable proportional hazards models were used to identify factors associated with switching, considering death and loss to follow-up as competing risks. Analyses were carried out using IBM SPSS version 26.ResultsOut of 149 PLWH, 18 (12.1%) switched to second-line ART with a cumulative incidence rate of 1.8 per 100 person-years. Significant factors for switching included being older than 33 years (HR: 1.45, 95% CI: 1.12–1.89), having WHO stage 3 disease (HR: 1.58, 95% CI: 1.21–2.06), and being on a TDF-FTC-EFV-based first-line regimen (HR: 1.35, 95% CI: 1.03–1.77). This switching rate is consistent with rates observed in other resource-limited settings, indicating it is neither exceptionally high nor low compared to similar contexts​.ConclusionsThe study highlights key factors associated with switching to second-line ART in Yemen, emphasizing the need for targeted interventions and continuous monitoring to enhance treatment outcomes. These findings are consistent with regional data from other resource-limited settings.

HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, Angola

The surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.

Efficacy of first-line ART regimens based on tenofovir in HIV-infected patients with pre-existing A62V mutation in reverse transcriptase.

The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 ‒ patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 ‒ patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.

Attrition from care and its predictors among women exposed to dolutegravir- and efavirenz-based first-line antiretroviral therapy in Ethiopia: a before-and-after study.

The effect of dolutegravir (DTG)-based regimens on reducing attrition from care among women enrolled in the prevention of mother-to-child transmission (PMTCT) care program is unknown. Therefore, this study aimed to compare the incidence of attrition among women exposed to DTG-based with those exposed to efavirenz (EFV)-based first-line antiretroviral therapy (ART) in Ethiopia. An uncontrolled before-and-after study was conducted involving 932 women (with 466 on EFV-based and 466 on DTG-based regimens) who were enrolled in the PMTCT care program from September 2015 to February 2023. The outcome variable was attrition (i.e., maternal death or loss to follow-up before their infants' final HIV status was determined). A Kaplan-Meier estimator was employed to estimate the probability of attrition. The Cox proportional hazards regression model was fitted to identify predictor variables. The adjusted hazard ratio (aHR) with the corresponding 95% confidence interval (CI) was calculated to examine the risk difference in the comparison groups. The cumulative incidence of attrition among women was 5.2% (3.0% for those placed in the DTG-based regimen arm and 7.3% for those placed in the EFV-based regimen arm). Women on DTG-based regimens had a 57% (aHR: 0.43; 95% CI: 0.23-0.80) lower risk of attrition from care compared to those on EFV-based regimens. Women who delivered their infants at home (aHR: 2.35; 95% CI: 1.14-4.85), had poor/fair adherence (aHR: 3.23; 95% CI: 1.62-6.45), had unsuppressed/unknown viral load status (aHR: 2.61; 95% CI: 1.42-4.79), and did not disclose their status to partners (aHR: 2.56; 95% CI: 1.34-4.92) had a higher risk of attrition from PMTCT care compared to their counterparts. The cumulative incidence of attrition among women receiving PMTCT care is optimal. In addition, the risk of attrition among women receiving DTG-based regimens is lower than that among women receiving EFV-based regimens. Thus, DTG-based first-line ART regimen supplementation should be sustained to achieve a national retention target of 95% and above.

Burden and predictors of anxiety disorder among HIV patients on ART in Nairobi Kenya

Anxiety disorders are prevalent among people living with Human Immunodeficiency Virus (HIV) globally, but data on the prevalence and factors associated with this mental illness are limited among HIV patients on antiretroviral therapy (ART) in Kenya. This study determined the prevalence and correlates of anxiety disorder among HIV patients receiving care and treatment at the Comprehensive Care Clinic (CCC) in Mbagathi Hospital in Nairobi, Kenya. This was a cross-sectional study where 205 eligible and consenting participants were systematically enrolled. The Beck Anxiety Inventory (BAI) Questionnaire was used to assess anxiety levels, with a score of 8 or more indicating moderate to severe anxiety. Structured questionnaires were used to collect information on factors associated with anxiety disorder. Descriptive statistics and logistic regression models were used to analyze data. Of the enrolled 205 patients, 122 (59.5%) were female. The median age and household size were 49 years (Interquartile range IQR 39–54) and 3 people (IQR 2–3) respectively. A large proportion of the participants, 169 (82.4%) were on the first-line ART regimen and the median duration on ART was 13 years (IQR 7–18). Nearly a third of the participants 60 (29.3%) had anxiety disorder. Male participants (adjusted odds ratio—aOR 0.33; 95% confidence interval—CI 0.13–0.78) were less likely to have anxiety disorder. Self-employment (aOR 5.57; 95% CI 2.17–20.06), larger households (aOR 1.48; 95%CI 1.11–2.03) and no history of tuberculosis infection (aOR 2.9; 95% CI; 1.29–6.96) were factors associated with having anxiety disorder. Among PLHIV receiving ART in Nairobi County, Kenya, there is a considerable burden of anxiety disorder which was associated with gender, occupation, household population size and history of tuberculosis infection.

Neurocognitive profile in HIV subjects on INSTI-regimen- one year follow up: Is there room for optimism?

The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of HIV-related neurocognitive disorders. Integrase strand transferase inhibitors (INSTI) are recommended and preferred first-line ART for the treatment of HIV-1 infection in ART-naïve subjects. This type of therapy regimen is expected to have higher CNS penetration, which may bring more cognitive stability or even make significant cognitive improvement in people with HIV. The study aimed to follow up on neurocognitive performance in HIV subjects on two types of INSTI therapy regimens at two-time points, one year apart. The study sample consisted of 61 ART naïve male participants, of which 32 were prescribed raltegravir (RAL) and 29 dolutegravir (DTG). There was no significant difference between subsamples according to the main sociodemographic (age, education level) and clinical characteristics (duration of therapy, nadir CD4 cells level, CD4 cells count, CD8 cells, CD4/CD8 ratio). For neurocognitive assessment, six measures were used: general cognitive ability (MoCA test), verbal fluency (total sum score for phonemic and category fluency), verbal working memory (digit span forward), cognitive capacity (digit span backwards), sustained attention (Color Trail Test 1), and divided attention (Color Trail Test 2). In both therapy groups (RAL and DTG), there was no significant decrease in neurocognitive achievement on all used measures over a one-year follow-up in both therapy groups. A statistically significant interactive effect of time and type of therapy was found on the measure of divided attention-DTG group showed slight improvement, whereas RAL group showed slight decrease in performance. During the one-year follow-up of persons on INSTI-based regimen, no significant changes in cognitive achievement were recorded, which suggests that the existing therapy can have a potentially positive effect on the maintenance of neurocognitive achievement.