First-line Antiretroviral Therapy Regimens 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.

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.

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.

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.

Population Effectiveness of Dolutegravir Implementation in Uganda: A Prospective Observational Cohort Study (DISCO), 48-Week Results.

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. 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. 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. 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. NCT04066036.

Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment. We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL. In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

Effect of Dolutegravir-Based First-Line Antiretroviral Therapy on Mother-to-Child Transmission of HIV Among HIV-Exposed Infants in Ethiopia: a Before-and-After Study.

Currently, Dolutegravir (DTG)-based regimens are administered to women on Option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect on reducing MTCT of human immunodeficiency virus (HIV) among HIV-exposed infants over the previously used Efavirenz (EFV)-based regimen is unknown. This study aimed to compare the effects of DTG-based and EFV-based regimens on the MTCT of HIV among HIV-exposed infants in Ethiopia. An uncontrolled before-and-after study design was conducted among 958 mother-infant pairs (479 on EFV-based and 479 on DTG-based regimens) enrolled in the prevention of mother-to-child transmission (PMTCT) care from September 2015 to February 2023. The outcome variable was the HIV infection status among the exposed infants. A log-binomial model was employed, and the proportion was computed to compare the incidence of MTCT of HIV in both groups. The risk ratio (RR) with a 95% confidence interval (CI) was calculated to assess the predictor variables. Mothers on DTG-based regimens were approximately 44% (adjusted risk ratio (aRR): 0.56; 95% CI: 0.44, 0.70) less likely to transmit HIV to their infants than those on EFV-based regimens. In addition, poor or fair adherence to antiretroviral therapy (ART) (aRR: 5.82; 95% CI: 3.41, 9.93), home delivery (aRR: 3.61; 95% CI: 2.32, 5.62), mixed feeding practice (aRR: 1.83; 95% CI: 1.45, 2.3) and not receiving antiretroviral prophylaxis (aRR: 3.26; 95% CI: 1.6, 6.64) were found to increase the risk of MTCT of HIV infection, whereas older maternal age (aRR: 0.93; 95% CI: 0.9, 0.96) was a protective factor. Mother-to-child transmission of HIV was less frequently observed in mother-infant pairs exposed to the DTG-based regimens as compared to those exposed to the EFV-based regimens. Thus, DTG-based first-line ART regimens supplementation should be sustained to achieve global and national targets for zero new infections in HIV-exposed infants.

Virological, weight, and drug resistance outcomes among patients initiating a dolutegravir-based first-line antiretroviral therapy regimen in Zimbabwe.

Dolutegravir (DTG)-based antiretroviral therapy (ART) is being scaled up in Africa. However, clinical experience with DTG and patterns of HIV drug resistance (HIVDR) are sparse in Zimbabwe. We assessed virological, weight, and HIVDR outcomes among individuals initiating on a DTG-based ART. We conducted a prospective cohort study among HIV-infected adult (≥18 years old) individuals attending care at Parirenyatwa hospital, Harare, Zimbabwe between October 2021 and April 2023. Viral load and weight were assessed at both baseline and follow-up (≥24weeks) visits. HIVDR genotyping was performed by Sanger sequencing among participants with virological failure (viral load ≥1000 copies/ml) at follow-up visit. Factors associated with weight gain were determined using logistic regression analysis on STATA 17.0. One hundred and seventy-two participants were enrolled in the study. The median [interquartile range (IQR) age was 39 (29-48)] years whilst the median (IQR) CD4 + cell count and log 10 viral load at enrolment was 175 (58-328) cells/μl and 5.41 (4.80-5.74), respectively. After a median (IQR) duration of 27 (25-30) weeks on DTG, of the 131 participants with follow-up viral load data available, 129 (98%) had viral load less than 1000 copies/ml and among the 2 (2%) participants with viral load at least 1000 copies/ml, no emergent HIVDR was detected. We observed a significant increase in weight among the participants. The average weight gain was 5.25 kgs ( P < 0.0001). Baseline CD4 + cell count at least 200 cells/μl was significantly associated with at a smaller weight gain [odds ratio (OR) = 0.26; 95% confidence interval (CI) 0.12-0.58, P = 0.001]. We found high virological suppression and an increased weight among people initiating on DTG in a resource-limited setting. Encouragingly, HIVDR to DTG remains rare.

Evaluating Antiretroviral Therapy Service Delivery Models Through Lot Quality Assurance Sampling in Central Uganda.

This study evaluated the effectiveness and responsiveness of differentiated Human Immunodeficiency Virus (HIV)/Acquired Immuno-Deficiency Syndrome (AIDS) service delivery models (DSDMs) implemented to enhance antiretroviral therapy (ART) access and outcomes for patients while addressing Tuberculosis (TB)-HIV integration, focusing on four of the five DSDMs currently implemented in Uganda. A descriptive cross-sectional survey was conducted in eight districts of central Uganda using Lot Quality Assurance Sampling approach from 7th to 23rd March 2023. We randomly sampled 2668 patients who have been on ART for at least 1 year in a Facility-Based Individual Management (FBIM) model or in a non-FBIM DSDM for at least one year. Data were collected through patient interviews and review of records in ART and DSDM registers as well as ART cards. We analyzed the data in proportions, comparing the selected ART outcome and responsiveness indicators between Community Client Led ART Distribution (CCLAD), Community Drugs Distribution Point (CDDP) and Fast-Track Drug Refill (FTDR) DSDMs with the standard care (FBIM) model. The ART outcome variables include patients retained in the 1st line of the ART regimen, patients in World Health Organization clinical stage 1 during the last facility visit, patients who had no CD4 request during the past 12 months, viral load suppression, ART adherence, and patients who reported that they did not experience HIV/AIDS-related symptoms in the past 6 months. The variables on TB care include screening for TB using the intensified case finding form and patients tested positive for TB. Responsiveness variables include the perceived; travel time for ART refill, travel distance for ART refill, convenience and flexibility during ART refill, cost of travel for ART refill, fear of being seen at ART refill point, waiting time before service, adequacy of service time, crowding and risk of infections, social support, ability to address ART treatment challenges, HIV status disclosure and barriers to access. Non-overlap in 95% confidence interval in indicator proportion between non-FBIM DSDM and FBIM means a statistically significant difference in proportion, or otherwise non-significant. Higher proportions of ART patients in the CCLAD and CDDP DSDMs adhered to ART, had suppressed viral load, and a lower TB prevalence than those in FBIM model. Additionally, more CCLAD and CDDP clients reported shorter travel time and distance to access ART than their counterparts in the FBIM model. Compared to FBIM model, higher proportions of those in CCLAD and CDDP also reported flexibility in ART refill scheduling, reduced transport costs, fewer privacy concerns, less HIV/AIDS-related stigma, shorter waiting times, more efficient services, decreased congestion at ART pickup sites, enhanced peer support, improved problem-solving assistance, and increased HIV status disclosure. The FTDR model outperformed FBIM in proportions with fewer requests for CD4 testing, viral load suppression, as well as proportions of clients who reported; shorter travel time, lower transportation cost, decreased privacy concerns, shorter waiting time, and efficient service provision. Compared to both CDDP and FTDR, the FBIM had a higher proportion of clients remain on the first-line ART regimen. Community-based DSDMs show responsiveness to clients' needs without compromising the effectiveness of ART care for patients. Although FTDR also demonstrates high effectiveness and responsiveness for clients on ART, there is potential for further improvement. Planners and implementers of ART programs should consider both demand- and supply-side innovations to sustain the continuation of DSDMs.

Low prevalence of archived integrase strand transfer inhibitors resistance associated mutations in Botswana before the roll out of dolutegravir based first line antiretroviral therapy.

We evaluated the prevalence of archived proviral drug resistance mutations (DRMs) associated with resistance to integrase strand transfer inhibitors (INSTIs) shortly before Botswana transitioned in 2016 to using dolutegravir (DTG)-based antiretroviral treatment in first-line regimens. We used the Stanford University HIV drug resistance database to analyze INSTI-resistance associated mutations (RAMs) in a large representative population-based cohort of adults recruited in 30 geographically dispersed communities as part of the Botswana Combination Prevention Project (BCPP) cohort from 2013 to 2018. A total of 5,144 HIV-1 proviral DNA sequences were included in our analysis; 1,281 sequences were from antiretroviral therapy (ART)-naïve individuals and 3,863 sequences were from non-nucleoside reverse transcriptase inhibitor (NNRTI) ART-experienced individuals. None of the sequences were from DTG-ART experienced participants. The overall prevalence of major INSTIs DRMs was 1.11% (95% CI 0.82-1.39%). The prevalence of INSTI DRMs in ART-naïve individuals was 1.64% (21/1,281) and 0.93% (36/3,863) in ART-experienced individuals. Major INSTI-RAMs detected in ART-naïve individuals were E138K (2/1,281; 0.16%), G140R (8/1,281;0.62%), E92G (2/1,281;0.16%), R263K (5/1,281; 0.4%), N155H (1/1,281; 0.08%), P145S (1/1,281;0.008%). Among the ART-experienced individuals, major INSTI RAMs detected were E138K (4/3,863; 0.10%), G140R (25/3,863;0.65%), G118R (2/3,863, 0.05%), R263K (4/3,863, 0.10%), T66I (1/3,863;0.03%), E138K + G140R (1/3,863, 0.03%|), G140R + R263K (1/3,863, 0.03%). High-level resistance to cabotegravir (CAB), elvitegravir (EVG), and raltegravir (RAL) was detected in 0.70, 0.16 and 0.06% of the individuals, respectively. Notably, bictegravir (BIC) and dolutegravir (DTG) showed no high-level resistance. The overall prevalence of archived INSTI RAMs in Botswana was low prior to transitioning to first-line DTG-based ART regimens, and did not differ between ART-naïve and ART-experienced individuals. Ongoing surveillance of INSTI DRMs in Botswana will allow for re-assessment of INSTI resistance risk following nationwide DTG rollout.

Levels and Predictors of Unsuppressed Viremia among People Living with HIV on ART in an Urban Population of North-Central Nigeria: A Retrospective Cross-sectional Study

Achieving viral suppression is crucial for the effective management of HIV. We investigated the prevalence and predictors of unsuppressed viremia among adults living with HIV (PLHIV) on antiretroviral therapy (ART) in the urban city of Jos, Plateau State, North-central Nigeria. A cross-sectional study was conducted with 2,748 PLHIV, comprising 1,902 females (69.2%) and 846 males (30.8%). The majority (71.0%) were aged 36-55 years. Most participants (88.1%) were on the first-line ART regimen tenofovir disoproxil fumarate-lamivudine-dolutegravir (TDF+3TC+DTG), with 6.0% on second-line regimens. The prevalence of unsuppressed viremia (viral load &gt;1,000 copies/mL) was assessed, and predictors were identified using chi-square tests and logistic regression analyses. Overall prevalence of unsuppressed viremia was 4.0% (110 participants), with higher proportions among males (5.6%) compared to females (3.3%) and among those aged 18-35 years (7.9%) compared to other age groups. PLHIV on first-line TDF+3TC+DTG ART had the lowest level of unsuppressed viremia (2.6%). Chi-square tests revealed significant associations between unsuppressed viremia and gender (χ2=7.67, p=0.01), age group (χ2=13.19, p=0.01), and ART regimen (χ2=110.97, p=0.0001). Multivariate logistic regression identified males (AOR=1.69; 95% CI: 1.12-2.56), younger age groups (18-35 years: AOR=12.96; 95% CI: 2.12-79.09 and 36-45 years: AOR=12.84; 95% CI: 3.70-44.64), and non-TDF+3TC+DTG regimens as significant predictors of unsuppressed viremia. The study highlights the effectiveness of the TDF+3TC+DTG regimen and the need for targeted interventions to address disparities in viral suppression, particularly among males and younger individuals. These findings are crucial for optimizing HIV treatment strategies and improving health outcomes for PLHIV in urban areas of low-and-middle-income countries.

Predictors of Viral Suppression among Adults Living with HIV/AIDS in Nigeria: A Retrospective Chart Review.

Over 1.6 million Nigerians have succumbed to the ravaging scourge of the acquired immunodeficiency syndrome (AIDS) epidemic since its discovery. Viral suppression (VS) then becomes a critical cost-effective human immunodeficiency virus (HIV) prevention strategy. We assessed the prevalence and predictors of VS. This retrospective case file review was conducted among adults (aged ≥18 years) living with HIV/AIDS who accessed care at a tertiary health facility in Northwestern Nigeria between January and December 2021. One thousand one hundred and twenty HIV/AIDS-eligible patients accessed care during the study. Their age ranged between 20 and 70 years with a mean of 43.83 ± 10.83 (95% confidence interval [CI]: 43.19-44.46). The patients were mostly female (728; 65.0), residing in urban areas (680; 60.7%), self-employed (440; 39.3%), married (712; 63.6%), receiving antiretroviral therapy (ART) for at most 14 years (916; 81.8%), on first-line ART regimen (812; 72.5%), in HIV clinical stage 1 (964; 86.1%), and with a baseline CD4 count of 199 cells/µl (453; 40.4%). The prevalence of VS of 64.3% (720/1120) was recorded in the study. The predictors of VS were disclosure of HIV status (odds ratio [OR] =2.4; 95% CI = 1.503-3.832), absence of opportunistic infections (OR = 2.6; 95% CI = 1.242-5.406), receiving ART for 15-29 years (OR = 2.1; 95% CI = 1.398-3.292), first-line ART regimen (OR = 3.7; 95% CI = 2.618-5.115), and adequate adherence (OR = 4.7; 95% CI = 3.324-6.766). VS was suboptimal among the study cohort with adequate adherence being its strongest predictor.

Characterization and outcomes of difficult-to-treat patients starting modern first-line ART regimens: Data from the ICONA cohort

ObjectivesTreatment failures to modern antiretroviral therapy (ART) raise concerns, as they could reduce future options. Evaluations of occurrence of multiple failures to modern ART are missing and their significance in the long run is unclear. MethodsPeople with HIV (PWH) in the ICONA cohort who started a modern first-line ART were defined as ‘difficult to treat’ (DTT) if they experienced ≥1 among: i) ≥2 VF (2 viral loads, VL>200 copies/mL or 1 VL>1000 copies/mL) with or without ART change; ii) ≥2 treatment discontinuations (TD) due to toxicity/intolerance/failure; iii) ≥1 VF followed by ART change plus ≥1 TD due to toxicity/intolerance/failure. A subgroup of the DTT participants were matched to PWH that, after the same time, were non-DTT. Treatment response, analysing VF, TD, treatment failure, AIDS/death, and SNAE (Serious non-AIDS event)/death, were compared. Survival analysis by KM curves and Cox regression models were employed. ResultsAmong 8061 PWH, 320 (4%) became DTT. Estimates of becoming DTT was 6.5% (95% CI: 5.8–7.4%) by 6 years. DTT PWH were significantly older, with a higher prevalence of AIDS and lower CD4+ at nadir than the non-DTT. In the prospective analysis, DTT demonstrated a higher unadjusted risk for all the outcomes. Once controlled for confounders, significant associations were confirmed for VF (aHR 2.23, 1.33–3.73), treatment failure (aHR 1.70, 1.03–2.78), and SNAE/death (aHR 2.79, 1.18–6.61). ConclusionA total of 6.5% of PWH satisfied our definition of DTT by 6 years from ART starting. This appears to be a more fragile group who may have higher risk of failure.

Burden of Anemia among Human Immunodeficiency Virus-Positive Adults on Highly Active Antiretroviral Therapy at Hawassa University Compressive Specialized Hospital, Hawassa, Ethiopia.

Anemia is the most common hematologic abnormality associated with human immunodeficiency virus (HIV)-infected patients and affects 60% to 80% of patients in late-stage disease. It has a considerable impact on the progression of HIV to advanced stages. This study aimed at assessing the burden of anemia in adult HIV-infected patients who are on highly active antiretroviral therapy (HAART) and have follow-up at Hawassa University Comprehensive Specialized Hospital (HUCSH) Antiretroviral therapy (ART) clinic. A hospital-based retrospective study was conducted among HIV-positive adults on HAART at Hawassa University Compressive Specialized Hospital. The systematic sampling method was used to choose a total of 244 study participants. Data on demographic characteristics, related factors of anemia, latest hemoglobin, CD4, and ART regimens were collected using a structured data abstraction format. The data were cleaned and analyzed using SPSS version 21.0 after being manually checked for completeness. Multivariable logistic regression was carried out to detect elements associated with anemia. A P value of <0.05 was used as a cutoff point to announce statistical significance. The records of 244 patients were examined in total. Anemia was present in 29.9% (95% CI 23.8-35.2) among adult HIV patients. Female sex (AOR: 2.576, 95% (CI: 1.295-5.127)), having tuberculosis (TB) (AOR: 4.873, 95% (CI: 1.534-15.484)), taking a zidovudine (ZDV)-containing ART regimen (AOR: 5.216, 95% (CI: 1.239-21.962)), having clinical WHO stage IV and III diseases (AOR: 3.077, 95% CI (1.244-7.612)), having body mass index (BMI) <18.5 kg/m2 (AOR: 2.391, 95% (CI: 1.138-5.023)), and taking cotrimoxazole prophylaxis (AOR: 3.860 95% (CI: 1.097-13.576)) were substantially linked to the development of anemia among adult HIV patients. Conclusion and Recommendation. This study showed that anemia is still a problem among HIV patients on HAART. The burden of anemia was found to be high among patients with advanced WHO clinical stages, having a BMI less than 18.5 kg/m2, TB/HIV coinfection, being on AZT-based ART regimens, and taking cotrimoxazole preventive therapy (CPT). Consequently, it is suggested that early preventative interventions, such as serial hemoglobin follow-up, iron supplementation, and education about dietary consumption, be undertaken targeting the aforementioned groups. In addition, the preferred first-line ART regimen as per the latest national and WHO guidelines is recommended, especially for the above groups.

Use of integrase inhibitors vs protease inhibitors is associated with improved HIV viral suppression

Current guidelines for antiretroviral therapy in pregnancy include the use of a dual-nucleoside reverse transcriptase inhibitor with either an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, although there is no designation of which is the preferred option. This study aimed to compare viral suppression at delivery among patients on dual-nucleoside reverse transcriptase inhibitors combined with either an integrase strand transfer inhibitor or a protease inhibitor. A hypothesis was made that the incidence of viral suppression is higher with the use of a dual-nucleoside reverse transcriptase inhibitor backbone combined with an integrase strand transfer inhibitor than with the use of a dual-nucleoside reverse transcriptase inhibitor backbone combined with a protease inhibitor. This study was an observational study of pregnant patients living with HIV who received prenatal care and delivered after 20 weeks of gestation at an urban safety net hospital. All pregnant patients with HIV were referred to a centralized clinic for HIV counseling, medication management, and prenatal care. Antiretroviral therapy was continued or initiated according to protocols based on national guidance. Among patients on a dual-nucleoside reverse transcriptase inhibitor backbone combined with integrase strand transfer inhibitor vs protease inhibitor at delivery, we compared the demographics and HIV disease characteristics, including year of diagnosis, viral load, and antiretroviral therapy class. The outcome of interest was viral suppression at delivery, defined as a viral load of <50 copies/mL. From January 2011 to December 2021, 604 patients on dual-nucleoside reverse transcriptase inhibitor met the inclusion criteria, including 411 patients (68%) on protease inhibitor and 193 patients (32%) on integrase strand transfer inhibitor at delivery. Demographic distribution was similar, and prenatal care was initiated at 12 weeks of gestation. Among the integrase strand transfer inhibitor group, 101 (17%) were on antiretroviral therapy at initiation of prenatal care compared with 169 (28%) in the protease inhibitor group. At delivery, the frequency of viral load suppression was higher among those on an integrase strand transfer inhibitor (147/193 [76%]) than among those on a protease inhibitor (275/411 [67%]) (odds ratio, 1.59; 95% confidence interval, 1.08-2.33). Among those with a detectable virus, quantitative viral load was not different. During the study period, the use of a protease inhibitor decreased, whereas the use of an integrase strand transfer inhibitor increased. Among pregnant patients living with HIV, viral suppression was more common among those on a dual-nucleoside reverse transcriptase inhibitor backbone combined with integrase strand transfer inhibitor than among those on a dual-nucleoside reverse transcriptase inhibitor backbone protease inhibitor at delivery. Our results support the use of dual-nucleoside reverse transcriptase inhibitor with integrase strand transfer inhibitor as a first-line antiretroviral therapy regimen in pregnancy.

How Hypertension Rates and HIV Treatment Outcomes Compare between Older Females and Males Enrolled in an HIV Treatment Program in Southern Nigeria: A Retrospective Analysis.

Studies show that treatment outcomes may vary among persons living with HIV. To fast-track the attainment of epidemic control across gender and age groups, the Accelerating Control of the HIV Epidemic (ACE-5) Project implemented in Akwa Ibom and Cross Rivers States, Nigeria, examined the hypertension rates and treatment outcomes of older adults living with HIV. The demographic and treatment characteristics of males and females ≥ 50 years living with HIV, who initiated antiretroviral therapy (ART) as of September 2021, were abstracted from medical records across 154 health facilities and community sites in Akwa Ibom and Cross River states, Nigeria. We compared these characteristics by sex using the chi-square test. The log-rank test was used to compare differences in their retention (i.e., being on treatment) and viral suppression (VS) rates [<1000 copies/Ml] in September 2022. Of the 16,420 older adults living with HIV (10.8% of the treatment cohort) at the time of the study, 53.8%, and 99.5% were on a first-line ART regimen. Among the 3585 with baseline CD4 documented (21.8% of the cohort), the median [IQR] CD4 count was 496 [286-699] cells/mm3, with more males having lower baseline CD4 than females [13.4% of males vs. 10.2% of females, p-value = 0.004]. In total, 59.9% received treatment at out-of-facility locations, with more males receiving treatment in this setting than females [65.7% vs. 54.8% p-value < 0.001]. Of those in whom blood pressure was assessed (65.9% of the treatment cohort), 9.6% were hypertensive, with males being less likely to be hypertensive [8.0% vs. 11.1% p-value < 0.001] than females. Overall, retention as of September 2022 was 96.4%, while VS was 99.0% and did not differ significantly by sex [retention: p = 0.901; VS: p = 0.056]. VS was slightly but not significantly higher among females than males (98.8% versus 99.2%; Aor = 0.79, 95%CI = 0.58-1.10, p = 0.17). Although older males and females living with HIV had similar treatment outcomes, hypertension screening was suboptimal and could impact long-term morbidity and mortality. Our study emphasizes the need to integrate noncommunicable disease screening and the management of hypertension in the care of older persons living with HIV.

Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1.

Antiretroviral therapy (ART) effectiveness is compromised by the emergence of HIV drug resistance mutations (DRM) and can lead to the failure of ART. Apart from intrinsic viral factors, non-compliance with drugs and/or the use of sub-optimum therapy can lead to the emergence of DRMs. In Pakistan HIV currently exists as a concentrated epidemic, however, ART coverage is very low, and drug adherence is poor. ART is selected assuming without baseline genotyping. Pakistan has recently seen a rise in treatment failures, but the country's actual burden of DRM is still unknown. In this study, we perform the genetic and drug resistance analysis of the pol gene from Pakistani HIV-positive ART-naïve and ART-experienced individuals. In this study, HIV-1 pol was sequenced from 146 HIV-1 positive individuals, divided into ART-naïve (n = 37) and ART-experienced (n = 109). The sequences were also used to determine HIV-1 subtypes, the prevalence of DRM, and pol genetic variability. DRM analysis identified numerous DRMs against reverse transcriptase inhibitors in both ART-naïve and ART-experienced groups, including a few that are classified as rare. Additionally, the ART-experienced group showed mutations associated with resistance to protease inhibitors. Genetic analysis showed negative selection pressure in both groups, but a higher rate of evolution in the ART-naïve group. High prevalence of DRMs, especially against previous first-line treatment in ART- naïve and the accumulation of DRMs in ART-experienced groups is concerning and warrants that a more extensive DRM survey be carried out to inform first-line and second-line ART regimen recommendations.