Search

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation. [ABSTRACT FROM AUTHOR]

Background Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens. Methods Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART. We compared non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48 months' risk and risk differences (RD) of MACE. Results Among 37 935 ART initiators (median age, 40 years; 23% female; 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months (RD, 0.50; 95% CI, 0.14–0.99), 18 months (RD, 0.53; 95% CI, 0.11–1.06), and 24 months (RD, 0.62; 95% CI, 0.04–1.29) for PI initiators, and at 12 (RD, 0.20; 95% CI, 0.03–0.37) and 18 months (RD, 0.31; 95% CI, 0.06–0.54) for INSTI initiators; the precision of estimates was limited for longer duration of follow-up. Conclusions Among ART initiators, PI-based and INSTI-based regimens were associated with higher short-term risk of MACE compared to NNRTI-based regimens. The pattern of association between INSTIs and PIs with excess risk of MACE was similar. [ABSTRACT FROM AUTHOR]

Abstract Bictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1.

Abstract Background The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. Methods In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). Results The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. Conclusions BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. Trial registration The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Introduction Methods Results Conclusions Prevention of cardiovascular disease is a major issue in the current management of people living with HIV. Concern is growing about the metabolic impact of integrase strand transfer inhibitors (INSTIs), which could lead to an increased risk of diabetes, but the data are conflicting. This is an updated version of our previous analysis, with longer follow‐up and new molecules.We retrospectively evaluated the incidence of new‐onset diabetes in people living with HIV starting combined antiretroviral therapy with an INSTI compared with non‐nucleoside reverse transcriptase inhibitors and protease inhibitors. Data were collected from the Dat'AIDS cohort study, a collaboration of 30 HIV treatment centres in France. We used a propensity score‐based inverse probability of treatment weighting approach to adjust for baseline characteristics between the two groups (INSTI and non‐INSTI).Between 2009 and 2021, a total of 12 150 people living with HIV were included. The incidence of diabetes was higher in the INSTI group than in the non‐INSTI group (hazard ratio 1.38; 95% confidence interval 1.07–1.77; p = 0.012). Regardless of the third drug, but to a greater extent for INSTIs, we observed a peak of new‐onset diabetes in the year following initiation of combined antiretroviral therapy.The incidence of diabetes was higher in people treated with integrase inhibitors than in those receiving other third agents. This increased risk occurred both during the first year of treatment and in the longer term. [ABSTRACT FROM AUTHOR]

Introduction: Homosexual transmission has contributed greatly to the current HIV-1 epidemic in Hebei province, China. Dolutegravir (DTG) will be conditionally used as a component of free antiretroviral therapy (ART) according to manual for national free anti-AIDS treatment drugs (2023 edition) issued by China in June 2023. However, current genetic characteristics and pretreatment drug resistance (PDR) to proteinase inhibitors (PIs), reverse transcriptase inhibitors (RTs) and integrase strand transfer inhibitors (INSTIs) of HIV-1 in this population have remained unclear. Methods: Serial consecutive cross-sectional analyses for HIV- 1 infection trend, genetic characteristics, PDR and molecular transmission networks were conducted from 2018 to 2022. All of participants were HIV-1- infected MSM newly diagnosed at the HIV surveillance points (HSPs) in Hebei, China. Evidence of PDR was confirmed using the world health organization (WHO) list for surveillance of drug resistance mutations. Results: In this study, a total of 14 HIV-1 subtypes were circulating in the HSPs of Hebei province, China. CRF01_ AE (51.9%, 350/675), CRF07_BC (30.4%, 205/675), B (6.2%, 42/675) and URFs (5.8%, 39/675) were the four most predominant subtypes among MSM. And, CRF07_BC (r > 0) and URFs (r > 0) indicated an increasing trend, respectively; however, CRF01_AE (r < 0) showed a decline trend. The overall prevalence of HIV-1 PDR showed a substantial increase from 6.3% in 2018 to 7.9% in 2022. The prevalence of NNRTI-PDR was the highest (5.8%, 39/675), followed by INSTIs (2.4%, 16/675), NRTIs (0.6%, 4/675) and PIs (0.3%, 2/675). Furthermore, extensive HIV-1 strains bearing PDR were circulating in the MSM population via molecular transmission networks for major HIV-1 subtypes, especially CRF01_AE and CRF07_BC. Discussion: Our findings reflect that HIV-1 epidemic in the MSM population is complex and severe in Hebei, China. Therefore, it is urgent for us to implement more effective intervention measures to limit the further dissemination of HIV-1, especially the spread of HIV-1 INSTI-PDR strains. [ABSTRACT FROM AUTHOR]

Bictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. Methods: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). Results: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. Conclusions: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. Trial registration: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391). [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus type 2 (HIV-2) is a particular subtype of HIV, which is endemic in West Africa and is characterized by a more indolent course than HIV-1. As people living with HIV-2 (PWH-2) are at risk for the development of acquired immunodeficiency syndrome and can transmit the virus, antiretroviral therapy is usually indicated. However, the optimal treatment of HIV-2 is unknown and historically the protease inhibitors (PIs) were a regular part of therapy. Nowadays, the use of integrase strand transfer inhibitors (INSTIs) in HIV-2 is increasing but the evidence supporting this approach is limited. In this narrative review, we outline the clinical data on the use of INSTI-containing antiretroviral therapy in HIV-2. We found that in the setting of treatment-naïve PWH-2, the use of INSTIs is successful, but also noted large heterogeneity in reported outcomes and that most cohorts are small with limited follow-up time. There is a lack of studies comparing the efficacy of INSTIs to other first-line options. For treatment-experienced PWH-2, the efficacy of INSTI is highly variable. [ABSTRACT FROM AUTHOR]

Abstract The human immunodeficiency virus type 2 (HIV-2) is a particular subtype of HIV, which is endemic in West Africa and is characterized by a more indolent course than HIV-1. As people living with HIV-2 (PWH-2) are at risk for the development of acquired immunodeficiency syndrome and can transmit the virus, antiretroviral therapy is usually indicated. However, the optimal treatment of HIV-2 is unknown and historically the protease inhibitors (PIs) were a regular part of therapy. Nowadays, the use of integrase strand transfer inhibitors (INSTIs) in HIV-2 is increasing but the evidence supporting this approach is limited. In this narrative review, we outline the clinical data on the use of INSTI-containing antiretroviral therapy in HIV-2. We found that in the setting of treatment-naïve PWH-2, the use of INSTIs is successful, but also noted large heterogeneity in reported outcomes and that most cohorts are small with limited follow-up time. There is a lack of studies comparing the efficacy of INSTIs to other first-line options. For treatment-experienced PWH-2, the efficacy of INSTI is highly variable.

Abstract Background Dolutegravir is an integrase strand transfer inhibitor that has been recommended for use in first-line antiretroviral regimens by the World Health Organisation and is currently being rolled out globally. There has been safety concerns with dolutegravir which has caused concern about its use in the general population. Dolutegravir first-line regimens have been used in South Africa since early 2020. Therefore, the aim of the present study was to assess the efficacy, safety, and tolerability of first-line dolutegravir-based antiretrovirals amongst adults living with HIV in Durban, South Africa. Methods This was a mixed-methods study, which comprised a cross-sectional survey and longitudinal retrospective follow-up of medical records. The study was conducted between October 2020 and January 2022. Data were described using descriptive and summary statistics. Bivariate logistic regression was applied to socio-demographic and clinical variables and crude odds ratios with a 95% confidence interval was calculated. Pearson chi-square tests, paired sample T-tests, and cross-tabulations were performed on selected variables. Results A total of 461 participants were enrolled in the study. There was a significant change in immunological outcomes (p

Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior–posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain–hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH. [ABSTRACT FROM AUTHOR]

Background: Dolutegravir is an integrase strand transfer inhibitor that has been recommended for use in first-line antiretroviral regimens by the World Health Organisation and is currently being rolled out globally. There has been safety concerns with dolutegravir which has caused concern about its use in the general population. Dolutegravir first-line regimens have been used in South Africa since early 2020. Therefore, the aim of the present study was to assess the efficacy, safety, and tolerability of first-line dolutegravir-based antiretrovirals amongst adults living with HIV in Durban, South Africa. Methods: This was a mixed-methods study, which comprised a cross-sectional survey and longitudinal retrospective follow-up of medical records. The study was conducted between October 2020 and January 2022. Data were described using descriptive and summary statistics. Bivariate logistic regression was applied to socio-demographic and clinical variables and crude odds ratios with a 95% confidence interval was calculated. Pearson chi-square tests, paired sample T-tests, and cross-tabulations were performed on selected variables. Results: A total of 461 participants were enrolled in the study. There was a significant change in immunological outcomes (p < 0.001) after dolutegravir initiation. Furthermore, an assessment of laboratory parameters showed that there was a significant decrease in cholesterol (p < 0.001) and increase in creatinine (p < 0.001) levels. Increased weight was shown by 60.7% of the participants but was not associated with age, gender, CD4 counts, and previous antiretroviral usage. The study found that 43.6% of the participants experienced at least one side-effect. A total of 21.6% and 23.2% of the participants experienced neuropsychiatric and central nervous system side-effects, respectively. In the bivariate analyses, only gender was shown to be associated with side-effects, and only 1.7% of the participants discontinued the study due to side-effects. Conclusion: Our results suggest that dolutegravir is effective, safe, and well tolerated in the study population. [ABSTRACT FROM AUTHOR]

Background: People living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, the existence of PLWH that show events of low‐level viremia (LLV) between 50 and 1000 copies/mL and with different virological consequences have been observed. Moreover, some reports indicate that LLV status can lead to residual immune activation and inflammation, leading to a higher occurrence of non‐AIDS‐defining events (nADEs) and other adverse clinical outcomes. Until now, however, published data have shown controversial results that hinder understanding of this phenomenon's actual cause(s) and origin(s). Integrase strand transfer inhibitors (INSTIs)‐based therapies could lead to lower LLV over time and, therefore, more effective virological control. Objectives: This review aims to assess recent findings to provide a view of the clinical significance and management of low‐level HIV viremia in the era of INSTIs. [ABSTRACT FROM AUTHOR]

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation.

Introduction: The impact of specific policies on HIV care has been scarcely investigated. In this study we aimed to analyze the impact of the Treatment For All policy (TFA‐2013) and the adoption of integrase strand transfer inhibitors (INSTIs‐2017) as first‐line therapy on clinical indicators of people living with HIV (PLHIV) in Brazil. Methods: We assessed the public database of Brazil's Ministry of Health and extracted data from 2009 to 2019. We investigated the impact of TFA and INSTIs with a time‐series analysis of four health indicators in PLHIV: antiretroviral treatment (ART) initiation with a CD4+ count >500/mm3; ART initiation <1 month after the first CD4+ measurement; viral load suppression (VLS); and treatment adherence. We explored trends over time by gender, age, macroregion of residency and municipal‐level social vulnerability index. Results: We included 753 316 PLHIV in 2019. Most were males (64.81%) in the 30–49 years age category (50.86%). We observed an overall improvement in all HIV clinical indicators, with notable impact of TFA on timely ART initiation and VLS, and mild impact of INSTIs on treatment adherence. Such improvements were heterogeneous, with remarkable gaps in gender, age and socioeconomic groups that have persisted over time. Indicators point to inferior outcomes among children, older adults, women and people living in socially vulnerable locations. Conclusions: Recent Brazilian public policies have had positive impacts on key HIV clinical indicators. However, our results highlight the need for specific policies to improve HIV care for children, older adults, women and socially vulnerable groups. [ABSTRACT FROM AUTHOR]

Background: Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods: A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results: The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137–0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk. Conclusion: Our findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies. [ABSTRACT FROM AUTHOR]

Aims: Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV‐1 RNA viral load (VL) during maintenance dual therapy. Methods: We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study. Results: At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow‐up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P =.015). Conclusion: A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin. [ABSTRACT FROM AUTHOR]

• Persons with HIV prescribed tenofovir alafenamide (TAF) were more likely to develop hypertensive disorders of pregnancy. • Antiretroviral therapy (ART) combinations of TAF and integrase strand transfer inhibitors (INSTI) were markedly associated with hypertensive disorders of pregnancy. • Excess gestational weight gain and diabetes were not more frequently observed in persons with HIV prescribed ART with TAF in combination with and without INSTI. We sought to determine if tenofovir alafenamide (TAF) was associated with excessive weight gain, diabetes (DM), and hypertensive disorders of pregnancy (HDP) in persons with HIV. This is a retrospective cohort study of pregnant persons with HIV prescribed antiretroviral therapy (ART) during the period of 01/01/2009 to 12/31/2020. χ 2 tests were used to compare the proportion of persons with excessive weight gain, DM, and HDP according to ART regimens. Excess total gestational weight gain was calculated using BMI and Institute of Medicine recommendations for weight gain in pregnancy. HDP included gestational hypertension and preeclampsia. Logistic regression models were used to determine predictors of excessive weight gain, DM, and HDP. We identified 189 pregnant persons prescribed ART with (30) and without TAF (1 5 9). The percentage of persons with excessive gestational weight gain was not significantly different in persons prescribed TAF (32 %) and other ART (17 %), p = 0.2. Persons prescribed TAF were more likely to have HDP (30 %) compared to other ART (9 %), p = 0.001. In the adjusted analysis, DM [aOR 6.2 (95 % CI 1.2–32.7)] and TAF exposure [aOR 3.2 (95 % CI 1.0–8.9)] were significantly associated with HDP. Despite similar gestational weight gain, persons with HIV prescribed TAF were more likely to have HDP. Further understanding of the metabolic and cardiovascular impact of ART recommended for use during pregnancy is needed. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. Objectives: We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Method: Longitudinal analysis of the Ndlovu Cohort Study including 36–48 months’ follow-up data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. Results: In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P 0.001; PLWH not on ART, BMI +1.8 kg/m2, P 0.001 and HIV-negative, BMI +1.3 kg/m2, P 0.001). Conclusion: The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality.

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS 95-95-95 target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load

Abstract Background Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among persons with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs on variation of liver steatosis and fibrosis in the ART-naïve person with HIV, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). Methods We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. Results 99 patients were included in our study. 82% were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p = 0.114). We observed a significant decrease in FIB-4 (p = 0.007) and NFS (p = 0.002). BARD score showed a significant increase (p = 0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (β= -0.08, 95% CI [-0.16 to -0.00], p = 0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. Conclusion INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the “return-to-health effect” observed with ART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in ART-naïve persons with HIV, possibly due to their effect on viral suppression.

The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010–2020 consisting of two nucleos(‐t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non‐nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50–499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non‐adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI‐ (n = 5119; 20.9%), PI‐ (n = 8935; 36.4%), and NNRTI‐use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non‐blip VLs were RNAneg (no RV) (n = 15 326; 63.4%), 1–19 cp/mL (n = 6318; 26.1%), 20–49 cp/mL (n = 1620; 6.7%), or <50 cp/mL with an unknown RV level (n = 922; 3.8%). In 193/1658 PWH (11.6%), the RV level was RNAneg in all VLs assessed. RV 1–19 cp/mL and 20–49 cp/mL (vs. RNAneg) were significantly associated with subsequent viral blips (respective odds ratio 2.66 and 4.90 [95% confidence intervals: 1.98–3.58 and 3.41–7.04]). Zenith VL and use of PIs (vs. INSTIs/NNRTIs) were associated with higher RV and blip odds. This large cohort study showed that blips were associated with higher preceding RV. Both the anchor type and factors previously linked to the latent viral reservoir were associated with RV, suggesting blips having a multifactorial origin. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether pregnant individuals with human immunodeficiency virus (HIV) prescribed integrase strand transfer inhibitor (INSTI) antiretrovirals (ARVs) achieve viral suppression faster than individuals taking non-INSTI regimens and to determine whether there were differences in viral suppression at delivery among INSTI ARVs. Methods: This is a retrospective cohort study of pregnant individuals with HIV who delivered a live infant during the study period (January 1, 2009-December 31, 2020). Patients' ARV therapy (ART) was classified as including INSTI or non-INSTI. We compared the proportion of individuals with viral suppression at delivery by group and individual INSTI ARVs using χ² and Fisher exact tests. A log rank test was used to compare time to viral suppression on ARVs. Results: During the study period, 168 individuals delivered a live infant. Most of the patients were diagnosed as having HIV before pregnancy and had taken ARVs before conception (76%), but fewer than half had an undetectable viral load at the first antenatal visit (45%). During pregnancy, 46% were prescribed INSTI and 54% were prescribed non-INSTI ARVs. Most had an undetectable HIV RNA viral load at delivery (75% INSTI and 72% non-INSTI, P = 0.7). The time to viral suppression was similar between groups (log rank test P = 0.43). Viral suppression at delivery was similar among INSTI ARVs: raltegravir (53%), elvitegravir (88%), dolutegravir (73%), and bictegravir (88%) (P = 0.13). Conclusions: Despite recommendations to prescribe INSTI in pregnancy for rapid viral suppression, we did not find a significant difference in time to viral suppression when pregnant individuals were taking non-INSTI ARVs. We did not find that one INSTI ARV was superior for viral suppression. [ABSTRACT FROM AUTHOR]

Real-world data evaluating weight changes in people living with HIV (PLWH) following switch to integrase strand transfer inhibitor (INSTI), specifically bictegravir (BIC), are limited. This retrospective cohort study analyzed weight changes upon switching to INSTI from non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) in treatment-experienced PLWH. Adult PLWH (≥18 years) treated with NNRTI or PI (non-switch cohorts) and those switching to INSTI (switch cohorts) between January 1, 2014 and August 31, 2019 were identified using IQVIA's Ambulatory Electronic Medical Records linked to a prescription drug claims database. The associations of switching to INSTI and individual INSTI agents with having ≥5% weight gain at 12 months of follow-up were evaluated, adjusting for demographics and baseline clinical characteristics. At 12 months of follow-up, PLWH in the NNRTI–INSTI switch cohort (n = 508) were more likely to have ≥5% weight gain over 12 months compared to the NNRTI non-switch cohort (n = 614; odds ratio, OR [95% CI], 1.7 [1.2–2.4]). Switching from NNRTI to dolutegravir (DTG: OR [95% CI], 2.1 [1.4–3.0]) or BIC (2.0 [1.0–4.2]) resulted in significantly higher odds of ≥5% weight gain. PI–INSTI switch (n = 295) and non-switch (n = 228) cohorts had similar proportions of PLWH with ≥5% (21.1–23.4%) or ≥10% (7.8–7.9%) weight gain, and no significant association was found between switching from PI to INSTI and weight gain. Weight gain and related metabolic health of PLWH switching from NNRTI to DTG or BIC should be closely monitored by clinicians. Further research is needed to assess other metabolic outcomes in PLWH remaining on PI and those who switch from PI to INSTI. [ABSTRACT FROM AUTHOR]

ObjectiveDolutegravir (DTG) is now a preferred component of first-line antiretroviral therapy (ART). However, prevalence data on natural resistance to integrase inhibitors [integrase strand transfer inhibitors (INSTIs)] in circulating non-subtype B HIV-1 in sub-Saharan Africa is scarce. Our objective is to report prevalence of pre-treatment integrase polymorphisms associated with resistance to INSTIs in an ART-naive cohort with diverse HIV-1 subtypes.DesignWe retrospectively examined HIV-1 integrase sequences from Uganda.MethodsPlasma samples were derived from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, reflecting enrollment from 2002 to 2010, prior to initiation of ART. HIV-1 integrase was amplified using nested-PCR and Sanger-sequenced (HXB2 4230-5093). Stanford HIVdb v8.8 was used to infer clinically significant INSTI-associated mutations. Human leukocyte antigen (HLA) typing was performed for all study participants.ResultsPlasma samples from 511 ART-naive individuals (subtype: 48% A1, 39% D) yielded HIV-1 integrase genotyping results. Six out of 511 participants (1.2%) had any major INSTI-associated mutations. Of these, two had E138T (subtype A1), three had E138E/K (subtype D), and one had T66T/I (subtype D). No participants had mutations traditionally associated with high levels of INSTI resistance. HLA genotypes A∗02:01/05/14, B∗44:15, and C∗04:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure.ConclusionWe detected no HIV-1 polymorphisms associated with high levels of DTG resistance in Uganda in the pre-DTG era. Our results support widespread implementation of DTG but careful monitoring of patients on INSTI with virologic failure is warranted to determine if unique mutations predict failure for non-B subtypes of HIV-1.

ObjectivesEvaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.MethodsBetween 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.ResultsMean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.ConclusionsThere is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior–posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain–hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways.

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Background: Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among persons with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs on variation of liver steatosis and fibrosis in the ART-naïve person with HIV, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). Methods: We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. Results: 99 patients were included in our study. 82% were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p = 0.114). We observed a significant decrease in FIB-4 (p = 0.007) and NFS (p = 0.002). BARD score showed a significant increase (p = 0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (β= -0.08, 95% CI [-0.16 to -0.00], p = 0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. Conclusion: INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the "return-to-health effect" observed with ART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in ART-naïve persons with HIV, possibly due to their effect on viral suppression. [ABSTRACT FROM AUTHOR]

In first-line antiretroviral therapy (ART) for human immunodeficiency virus (HIV) treatment, some subgroups of patients may respond better to an efavirenz-based regimen than an integrase strand transfer inhibitor (InSTI)-based regimen, or vice versa, due to patient characteristics modifying treatment effects. Using data based on nearly 16,000 patients from the North American AIDS Cohort Collaboration on Research and Design from 2009–2016, statistical methods for precision medicine were employed to estimate an optimal treatment rule that minimizes the 5-year risk of the composite outcome of acquired immune deficiency syndrome (AIDS)-defining illnesses, serious non-AIDS events, and all-cause mortality. The treatment rules considered were functions that recommend either an efavirenz- or InSTI-based regimen conditional on baseline patient characteristics such as demographic information, laboratory results, and health history. The estimated 5-year risk under the estimated optimal treatment rule was 10.0% (95% confidence interval (CI): 8.6, 11.3), corresponding to an absolute risk reduction of 2.3% (95% CI: 0.9, 3.8) when compared with recommending an efavirenz-based regimen for all patients and 2.6% (95% CI: 1.0, 4.2) when compared with recommending an InSTI-based regimen for all. Tailoring ART to individual patient characteristics may reduce 5-year risk of the composite outcome compared with assigning all patients the same drug regimen. [ABSTRACT FROM AUTHOR]

Integrase strand transfer inhibitors (INSTIs), including raltegravir (RAL), dolutegravir (DTG), elvitegravir (EVG), bictegravir (BIC), and cabotegravir (CAB), are increasingly used, given excellent data on their efficacy, effectiveness, and tolerability profile in adults, while data in children are accumulating. To review the most recent evidence on the efficacy, effectiveness, safety, and resistance of INSTIs in children, a quick narrative review of the available literature data was performed using the MEDLINE/PubMed and Scopus databases, including only English-language studies, published between 2009 and 2022. Six studies (259 children) on RAL use, 17 studies (3,448 children) on DTG, 2 studies (73 children) on EVG, and 1 study (102 children) on BIC were retrieved. Results on efficacy and effectiveness were close to those reported in adult studies, suggesting similarities between children and adult population. Resistance to RAL was detected in four studies, ranging between 5.0% to 35.3% of participants. In four studies resistance to DTG occurred in 12.4% to 22% of children. Adverse events to RAL have been uncommon reported. In studies on EVG, 8% to 74% of children developed uveitis, nausea, or abdominal pain. In DTG studies, the proportion of weight gain ranged from 10% to 87%, and neuropsychiatric effects ranged 1% to 16% of participants. One BIC study reported adverse events >10% of participants. The evidence supports high efficacy and low toxicity of INSTIs in pediatric and adolescent populations. [ABSTRACT FROM AUTHOR]

BackgroundIntegrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for human immunodeficiency virus (HIV) management. Although studies have suggested associations between INSTIs and weight gain, women living with HIV (WLHIV) have been underrepresented in research. We evaluated the effect of switching or adding INSTIs among WLHIV.MethodsWomen enrolled in the Women's Interagency HIV Study (WIHS) from 2006-2017 who switched to or added an INSTI to ART (SWAD group) were compared to women on non-INSTI ART (STAY group). Body weight, body mass index (BMI), percentage body fat (PBF), and waist, hip, arm, and thigh circumferences were measured 6-12 months before and 6-18 months after the INSTI switch/add in SWAD participants, with comparable measurement time points in STAY participants. Linear regression models compared changes over time by SWAD/STAY group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen.ResultsWe followed 1118 women (234 SWAD and 884 STAY) for a mean of 2.0 years (+/- 0.1 standard deviation [SD]; mean age 48.8 years, SD +/- 8.8); 61% were Black. On average, compared to the STAY group, the SWAD group experienced mean greater increases of 2.1 kg in body weight, 0.8 kg/m2 in BMI, 1.4% in PBF, and 2.0, 1.9, 0.6, and 1.0 cm in waist, hip, arm, and thigh circumference, respectively (all P values < .05). No differences in magnitudes of these changes were observed by INSTI type.ConclusionsIn WLHIV, a switch to INSTI was associated with significant increases in body weight, body circumferences, and fat percentages, compared to non-INSTI ART. The metabolic and other health effects of these changes deserve further investigation.

BackgroundGuidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTIs) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States.SettingWe examined 2 groups of PLWH at 8 clinics who initiated ART regimens (August 1, 2013-March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced.MethodsThe outcome in this longitudinal cohort study was VF, defined as a viral load of ≥400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models.ResultsAmong 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The hazard ratios for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95% CI: 0.2 to 0.6) among previously treatment-naive PLWH and was 0.60 (95% CI: 0.4 to 0.8) among treatment-experienced PLWH.ConclusionsThe proportion of previously treatment-naive PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naive and treatment-experienced PLWH.

No abstract available.

Summary: Background: The integrase strand transfer inhibitor (INSTI) dolutegravir is recommended in World Health Organization guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy (ART) in Johannesburg, South Africa. Methods: We conducted a prospective cohort study of adults (≥16 years) of black African ancestry with HIV who initiated ART between January 2010–December 2020. Patients were propensity score-matched 1:1 (unexposed i.e. remaining on efavirenz: exposed i.e. switched from efavirenz to dolutegravir) on sex, age, months on ART, first ART regimen, haemoglobin, body mass index (BMI), blood pressure, viral load and CD4 count. We used linear regression to assess the effect of switching from efavirenz to dolutegravir on weight change and hypertension 12 months after exposure. Findings: We matched 794 patients switching to dolutegravir to 794 remaining on efavirenz. Exposed patients had a higher mean change in weight (1.78 kg; 95% confidence interval (CI):1.04,2.52 kg) from start of follow-up to 12 months vs. unexposed. We also found a 14.2 percentage point increase (95% CI: 10.6,17.7) in the risk of hypertension in those exposed to dolutegravir vs those that remained on efavirenz. Interpretation: In a real-world population, patients gained more weight and were at higher risk of hypertension after switching from efavirenz to dolutegravir than those remaining on efavirenz. Longer follow-up is needed, however, to determine if INSTI-associated weight gain is associated with changes in non-communicable disease risk over the long-term, or whether weight gain is sustained, as seen in clinical trials. Funding: This study has been made possible by the generous support of the American People and the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID), under the terms of cooperative agreement cooperative Agreement 72067419CA00004. In addition to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1K01MH105320-01A1.

Background Integrase strand transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH). Less is known about the risk of other metabolic outcomes such as diabetes mellitus and hyperglycemia. Methods IBM® MarketScan® databases for commercially and Medicaid-insured adults were used to identify PWH newly initiating antiretroviral therapy (ART). The primary outcome was a composite of new-onset diabetes mellitus/hyperglycemia in the 6 months following ART initiation and was identified using International Classification of Disease, Ninth revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis and procedure codes and Current Procedural Terminology, 4th Edition (CPT-4) codes. To examine the relationship between INSTI use and the composite outcome, we estimated the risk using Cox proportional hazards models with calendar time-specific standardized mortality ratio weights. Results Of 42 382 PWH who initiated ART between 1 July 2007 and 30 June 2018, 22 762 (54%) were treated with INSTI-based regimens. Mean age was 38 years, 74% were male, and 19% were Medicaid insured. PWH on INSTIs were 31% more likely to develop new-onset diabetes mellitus/hyperglycemia (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15–1.48]) compared with those who initiated non–INSTI-based regimens. When examined individually, the highest risk was associated with elvitegravir (HR, 1.54; 95% CI, 1.32–1.97; P <.001) and the lowest risk with raltegravir (HR, 1.19; 95% CI, 1.03–1.37; P =.02). Conclusions INSTI use was associated with increased risk of new-onset diabetes mellitus/hyperglycemia in the 6 months following ART initiation. [ABSTRACT FROM AUTHOR]

Integrase strand transfer inhibitor (INSTI)-containing regimens in HIV-1- infected patients have experienced a global increase. Recently, WHO has emphasized the need to fast-track the transition to dolutegravir (DTG)- based antiretroviral (ARV) treatments. However, continued surveillance of INSTI resistance is recommended. In this study, clinical, epidemiological, and virological features associated with INSTI resistance diagnosed in Spain were analyzed. Samples collected between 2008 and 2021 from HIV-1-infected patients were analyzed in integrase, protease, and reverse transcriptase using Sanger population sequencing. ARV drug resistance was evaluated with the Stanford University HIVdb program. Among 2,696 patients, 174 (6.5%) had INSTI resistance, all of them to first-generation INSTIs, and 71 (2.6%) had also resistance to second-generation INSTIs. Of these, only 5 individuals were exposed to DTG as the only INSTI, in whom resistance development was associated with poor treatment adherence and/or resistance to other ARV classes. Of newly HIV-1-diagnosed individuals, 0.92% harbored INSTI-resistant viruses, with low prevalences maintained along time, and only one had low-level resistance to DTG. Persons who inject drugs, age over 39 years, resistance to other ARV classes, and longer time from diagnosis were associated with INSTI resistance (p < 0.001). Non-subtype B INSTI-resistant viruses lacked the Q148H + G140S resistance pathway and showed lower INSTI resistance levels than subtype B viruses. In conclusion, INSTI resistance is uncommon and associated with long-term infections, older age and additional resistance to other ARV drug classes, and is rare in newly diagnosed HIV-1 infections. Our results also support the preferential use of DTG-containing regimens in first-line treatments, although surveillance of INSTI resistance is encouraged. [ABSTRACT FROM AUTHOR]

• The prevalence of PDR and resistance mutations to INSTIs is currently low. • ADR to 2nd-generation INSTIs showed an increasing and then decreasing time trend. • CAB had the highest resistance among 2nd-generation INSTIs. Assessing the prevalence of resistance and drug resistance mutations (DRMs) in HIV/AIDS patients towards integrase strand transfer inhibitors (INSTIs), particularly the 2nd-generation INSTIs, provides evidence for rational clinical drug use. A systematic search was conducted on five databases to identify relevant literature reporting original data on INSTIs resistance. Meta-analyses, cumulative meta-analyses, subgroup analyses and meta-regression analyses were performed using selected models based on the results of heterogeneity tests. A total of 81 studies were included in this analysis. The prevalence of pre-treatment drug resistance (PDR) to 1st-generation INSTIs and 2nd-generation INSTIs were 0.41% (95% CI: 0.19%–0.70%) and 0.04% (95% CI: 0.00%–0.13%), respectively; and the prevalence of acquired drug resistance (ADR) were 7.60% (95% CI: 3.54%–12.92%) and 4.93% (95% CI: 1.78%–9.36%), respectively, and ADR showed an increasing and then decreasing time trend. The results of subgroup analyses showed differences in ADR to 2nd-generation INSTIs between regions and economic levels, with the highest ADR of 12.83% (95% CI: 3.24%–27.17%) in the European region. DRMs varied among HIV patients and reduced drug sensitivity to varying degrees. The prevalence of PDR and DRMs in 2nd-generation INSTIs is currently low, but as the use of DTG-based ART expands, population-level drug resistance monitoring and individual-level genetic testing should be strengthened in order to maximise treatment efficacy. Additionally, attention should be paid to ADR to INSTIs to provide personalised treatments for HIV-infected patients. [Display omitted] [ABSTRACT FROM AUTHOR]

More than fifteen million women with the human immunodeficiency virus type-1 (HIV-1) infection are of childbearing age world-wide. Due to improved and affordable access to antiretroviral therapy (ART), the number of in utero antiretroviral drug (ARV)-exposed children has exceeded a million and continues to grow. While most recommended ART taken during pregnancy suppresses mother to child viral transmission, the knowledge of drug safety linked to fetal neurodevelopment remains an area of active investigation. For example, few studies have suggested that ARV use can be associated with neural tube defects (NTDs) and most notably with the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG). After risk benefit assessments, the World Health Organization (WHO) made recommendations for DTG usage as a first and second-line preferred treatment for infected populations including pregnant women and those of childbearing age. Nonetheless, long-term safety concerns remain for fetal health. This has led to a number of recent studies underscoring the need for biomarkers to elucidate potential mechanisms underlying long-term neurodevelopmental adverse events. With this goal in mind, we now report the inhibition of matrix metalloproteinases (MMPs) activities by INSTIs as an ARV class effect. Balanced MMPs activities play a crucial role in fetal neurodevelopment. Inhibition of MMPs activities by INSTIs during neurodevelopment could be a potential mechanism for adverse events. Thus, comprehensive molecular docking testing of the INSTIs, DTG, bictegravir (BIC), and cabotegravir (CAB), against twenty-three human MMPs showed broad-spectrum inhibition. With a metal chelating chemical property, each of the INSTI were shown to bind Zn++ at the MMP’s catalytic domain leading to MMP inhibition but to variable binding energies. These results were validated in myeloid cell culture experiments demonstrating MMP-2 and 9 inhibitions by DTG, BIC and CAB and even at higher degree than doxycycline (DOX). Altogether, these data provide a potential mechanism for how INSTIs could affect fetal neurodevelopment.

Dolutegravir (DTG) is a preferred drug for initial treatment of human immunodeficiency virus type 1 infection. We present next-generation sequencing analysis of integrase genotypes during a period of virologic failure in a treatment-naive man who initiated tenofovir disoproxil fumarate/emtricitabine plus DTG.

Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use. Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort. Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed. Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7–2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106–124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160–188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04–1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18–2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00–0.99/1000 PYFU). Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs.

Abstract Background Potential drug–drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus (HIV; PLWH). Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs). Methods This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface. Results Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, P

Integrase strand transfer inhibitor (INSTI)-containing regimens in HIV-1-infected patients have experienced a global increase. Recently, WHO has emphasized the need to fast-track the transition to dolutegravir (DTG)-based antiretroviral (ARV) treatments. However, continued surveillance of INSTI resistance is recommended. In this study, clinical, epidemiological, and virological features associated with INSTI resistance diagnosed in Spain were analyzed. Samples collected between 2008 and 2021 from HIV-1-infected patients were analyzed in integrase, protease, and reverse transcriptase using Sanger population sequencing. ARV drug resistance was evaluated with the Stanford University HIVdb program. Among 2,696 patients, 174 (6.5%) had INSTI resistance, all of them to first-generation INSTIs, and 71 (2.6%) had also resistance to second-generation INSTIs. Of these, only 5 individuals were exposed to DTG as the only INSTI, in whom resistance development was associated with poor treatment adherence and/or resistance to other ARV classes. Of newly HIV-1-diagnosed individuals, 0.92% harbored INSTI-resistant viruses, with low prevalences maintained along time, and only one had low-level resistance to DTG. Persons who inject drugs, age over 39 years, resistance to other ARV classes, and longer time from diagnosis were associated with INSTI resistance (p

Objective: To describe weight changes with integrase strand transfer inhibitor (INSTI) therapy. Data Sources: A literature search was performed (through December 15, 2021) using the PubMed and CINAHL databases using the search terms: "integrase inhibitors," "integrase strand transfer inhibitors," and "weight." Study Selection and Data Extraction: Studies were included that provided relevant information on weight or body mass index (BMI) changes on INSTI therapy. Controlled or observational studies comparing different INSTI therapies or compared INSTI therapy to another class of antiretroviral therapy were included. Data Synthesis: Forty-three articles met criteria for inclusion, and data are presented. Although some trials have observed similar weight gains between INSTI, protease inhibitor, and non-nucleoside inhibitor therapies, the increase appears to be greater with INSTI therapy, particularly during initiation of therapy. Risk factors for weight gain with INSTI therapy include female gender, lower CD4 count, and combined use of tenofovir alafenamide. Within the INSTI class, dolutegravir and bictegravir appear to have the greatest propensity for weight gain. Relevance to Patient Care and Clinical Practice: INSTI-based therapies are the preferred initial management of HIV infection. Discerning the factors contributing to weight changes on INSTI therapy and risks of associated healthrelated outcomes is important to both the management of weight gain and HIV medical management. Conclusions: Within the INSTI class, dolutegravir and bictegravir may be associated with the greatest risk for weight gain particularly when combined with tenofovir alafenamide. Further research is needed to determine mechanisms for observed weight changes and any contributions to clinically significant metabolic and cardiovascular adverse outcomes associated with INSTI therapy. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) regimens containing integrase strand transfer inhibitors (INSTIs) are the recommended treatment for human immunodeficiency virus type 1 (HIV-1)-infected patients in the most recent guidelines in China. In this study, we investigated INSTI resistance mutations in newly diagnosed therapy-naive HIV-positive patients in Baoding City, Hebei Province (China) to provide guidance for implementing routine INSTIassociated HIV-1 genotypic resistance testing. Plasma samples were collected from HIV-1-infected patients without treatment at Baoding People's Hospital from January 2020 to December 2021. The part of HIV-1 pol gene encoding integrase was amplified, sequenced, and analyzed for INSTI resistance. Clinical data including demographic data, CD4+ T cell counts, HIVRNA loads, and resistance mutations were collected. Treatment-naïve HIV-1 patients (n = 131) were enrolled. We identified ten genotypes, and the predominant genotype was CRF01_AE in 67 patients (51.15%), CRF07_ BC in 39 patients (29.77%), subtype B in 11 patients (8.40%), and other subtypes (CRF68_01B, 3.82%; CRF55_01B, 1.53%, CRF80_0107, 1.53%; URFs 1.53%; and CRF103_01B, CRF59_01B, and CRF65_cpx, 1.4% each). Four major (E138A, R263k, G140S, and S147G) and three accessory (H51Y, Q146QL, and S153F) INSTI-resistance mutations were observed (genotype CRF01_AE, three patients; genotype B, one patient; and genotype CRF07_BC, one patient), resulting in different degrees of resistance to the following five INSTIs: raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. The overall resistance rate was 3.82% (5/131). All INSTI-resistant strains were crossresistant. The primary INSTI drug resistance rate among newly diagnosed HIV-infected patients in Baoding was low, but monitoring and research on HIV INSTI resistance should be strengthened in Baoding because INSTI-based regimen prescriptions are anticipated to increase in the near future. [ABSTRACT FROM AUTHOR]

Background: This study explores the relationship between different ART therapy based on NRTIs, and inflammatory markers, along with fasting blood glucose levels in treatment-naïve people living with HIV (PLWH)., Methods: We retrospectively analyzed the variations in fasting blood glucose and inflammatory markers and their relationship with different ART regimens in 497 treatment-naïve PLWH at the ART clinic of Zhongnan Hospital of Wuhan University from June 2018 to March 2022., Results: From baseline to 24 months, fasting blood glucose, systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV) and lymphocyte-to-monocyte ratio (LMR) in PLWH receiving ART increased, while neutrophillymphocyte ratio (NLR) decreased ( p < .05). In the NNRTIs group, fasting blood glucose, SII, PIV and LMR were higher than before ( p < .05). In the INSTIs group, fasting blood glucose and LMR increased ( p < .05), while NLR was lower ( p < .05). Compared to the INSTIs, fasting blood glucose in the NNRTIs group was higher at 12 and 24 months ( p < .05). At 24 months, both NLR and SII were higher in the NNRTIs group than in the INSTIs group ( p < .05)., Conclusions: Despite the virus suppression, fasting blood glucose and certain inflammatory markers in PLWH can gradually increase. Compared to NNRTIs, the INSTIs regimen was associated with favorable alterations in the levels of glucose and inflammatory markers., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS "95-95-95" target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (=18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)--M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)--K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTIbased antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana. [ABSTRACT FROM AUTHOR]