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Introduction: Human immunodeficiency virus HIV causes a well-known global disease, acquired immunodeficiency syndrome (AIDS), which has a high disease burden in Africa. HIV infection is known to be associated with oxidative stress, which may contribute to disease severity. However, the effect of HAART is equivocal, and requires more studies. 8-hydroxy-2-deoxyguanosine (8-OHdG), a useful biomarker to assess oxidative DNA damage in biological fluids, was therefore measured in this study., Objectives: The study measured 8-OHdG in HIV seronegative and seropositive participants and correlated it with the duration of HAART., Research Question: Does HIV infection have an effect on oxidative DNA damage? Does HAART have an effect on oxidative DNA damage? Does HAART duration have an effect on oxidative DNA damage?, Methods: This was a cross-sectional study consisting of 99 participants in 4 strata: 20 HIV seronegative, 25 HAART naïve, 26 on HAART <5 years, and 28 on HAART >5 years. Those on HAART were all on Tenofovir, Lamivudine, and Dolutegravir (TLD) combination. The questionnaires were administered, and blood samples were collected from all the participants. The serum 8-OHdG was measured with enzyme-linked immunosorbent assay in all the participants. The universal biosafety standards were strictly adhered to. The data were collected and analyzed with SPSS 2016 version., Results/discussion: The serum levels of 8-OHdG of the participants were shown below. Our findings showed higher 8-OHdG in HIV patients than the Controls and is much higher in HAART naïve when compared with those on HAART (p = 0.005). The serum 8-OHdG and HAART duration were compared and showed a statistically significant negative correlation (r = - 0.331, p= 0.014)., Conclusion: This study found that HIV infection causes oxidative DNA damage which is more in patients who have not started HAART than those on HAART. This showed that the TLD-HAART regimen reduces HIV-associated oxidative stress over time, though not completely. This finding further supports a critical role of oxidative stress in HIV infection, a protective effect of HAART, and a potential role of antioxidants that requires further research., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: People with HIV (PWH) are living longer directly related to benefits of highly effective antiretroviral therapy (ART). However, concurrent with improved longevity is the growing prevalence of metabolic comorbidities that drive morbidity and mortality among PWH. There is an increasing repertoire of treatment options for metabolic disorders. Thus, it is important for clinicians to understand the drug-drug interactions (DDIs) between ART and treatments for metabolic disorders., Areas Covered: This review will discuss DDIs between contemporary ART and agents used to treat metabolic syndrome (diabetes, dyslipidemia, obesity and hypertension). Literature review of published and unpublished data from manuscripts, conference proceedings, regulatory submissions, and drug prescribing information were conducted from the following sources: PubMed, Google, and Google Scholar through January 2024., Expert Opinion: People with HIV have a high prevalence of metabolic disorders. Most significant DDIs between ART and treatments for metabolic disorders are unidirectional with ART as perpetrators, rather than victims, such that careful selection of ART with low DDI propensity can address the concern. However, there are data gaps with DDI data for long-acting ART as well as newer oral and injectable medications for diabetes and weight loss. Nanotechnology-based drug delivery platforms hold promise to address some problematic DDIs.

Background: Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine., Methods: The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508)., Results: Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n=165) or the dual therapy arm (n=171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P=0.04). Two toxicity-related events led to discontinuation in each group., Interpretation: Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Combination antiretroviral therapy (ART) with at least three different drugs has become the standard of care for people with HIV (PWH) due to its exceptional effectiveness in viral suppression. However, many ART drugs have been reported to associate with neuropsychiatric adverse effects including depression, especially when certain genetic polymorphisms exist. Pharmacogenetics is an important consideration for administering combination ART as it may influence drug efficacy and increase risk for neuropsychiatric conditions. Large-scale longitudinal HIV databases provide researchers opportunities to investigate the pharmacogenetics of combination ART in a data-driven manner. However, with more than 30 FDA-approved ART drugs, the interplay between the large number of possible ART drug combinations and genetic polymorphisms imposes statistical modeling challenges. We develop a Bayesian approach to examine the longitudinal effects of combination ART and their interactions with genetic polymorphisms on depressive symptoms in PWH. The proposed method utilizes a Gaussian process with a composite kernel function to capture the longitudinal combination ART effects by directly incorporating individuals' treatment histories, and a Bayesian classification and regression tree to account for individual heterogeneity. Through both simulation studies and an application to a dataset from the Women's Interagency HIV Study, we demonstrate the clinical utility of the proposed approach in investigating the pharmacogenetics of combination ART and assisting physicians to make effective individualized treatment decisions that can improve health outcomes for PWH., (© The Author 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4 + cell count was 1,235 cells/mm 3 [ n = 51] at baseline, 1,690 cells/mm 3 ( n = 41) at Week 48, and 1,280 cells/mm 3 ( n = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.

Highly effective antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) care in the past 3 decades. 30 years ago, how many would have imagined that a single-tablet daily ART regimen containing different drug classes could achieve sustained HIV-1 suppression and halt disease progression to acquired immunodeficiency syndrome (AIDS)? Despite this remarkable achievement, challenges in HIV care remain that require further innovation for ART. In this review, we focus on newly approved antiretroviral agents and those undergoing phase 2/3 clinical trials. These new antiretrovirals hold great promise to expand treatment options and fill gaps in HIV care., Competing Interests: Disclosure The authors declared no potential conflicts of interest with respect to this article. Y. Li and M. Choudhary report no competing interests related to this work. J.W. Mellors is a consultant to Gilead Sciences, has received grant support to the University of Pittsburgh from Gilead Sciences, United States, is a founder and share option holder of Infectious Disease Connect and owns shares of Galapagos, NV and MingMed, Inc, unrelated to the current work. Y. Li is supported by Rustbelt CFAR (Case Western Reserve University/University Hospitals Cleveland Medical Center and University of Pittsburgh, P30 AI036219). Y. Li is a topic editor for DynaMed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The number of options for effective antiretroviral therapy (ART) is steadily increasing. Although older regimens may achieve the goal of virologic suppression, newer options can offer advantages in safety, tolerability, and convenience. In this article, we offer guiding principles for switching ART, highlighting reasons to pursue a switch and key factors to consider when selecting a new regimen., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Genvoya, Biktarvy and Dovato are novel single-tablet antiretroviral therapy(ART). The aim of this study is to explore the therapeutic effects of these novel drugs on HIV/AIDS., Main Methods: This retrospective cohort study, conducted at a single center, included a total of 200 HIV-treated patients who transitioned to these new antiretroviral drugs from July 2021 to August 2023. Data were extracted from electronic medical records at Ditan Hospital. The Genvoya group comprised 22 patients, and all subsequent switches in this group were to Biktarvy. The primary HAART group consisted of 178 patients initially treated with a first-line triple Highly Active Antiretroviral Therapy (HAART) regimen during the same period. This group was further subdivided into HAART+Dovato, HAART+Biktarvy, and HAART+Genvoya groups based on the switching regimen. The primary outcomes focused on changes in viral load and immune efficacy, while secondary safety indicators included blood/liver function, lipid parameters, renal function, blood glucose, blood uric acid, etc. KEY FINDINGS: The viral suppression rate was 100 % after the drug change treatment, and CD4+ T cell counts increased significantly across all four groups. Over the 6-month treatment period, there were increases in creatinine (Cr), low-density lipoprotein (LDL), high-density lipoprotein (HDL), erythrocyte count, and glomerular filtration rate (eGFR). Conversely, Alanine transaminase (ALT), Aspartate aminotransferase (AST), C-reactive protein (CRP), albumin (ALB), and blood glucose (Glu) levels decreased., Significance: Genvoya, Biktarvy and Dovato are recommended for the treatment of HIV/AIDS and have a good safety profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In China, non-nucleoside reverse transcriptase inhibitors (NNRTIs) are integral to the antiretroviral therapy (ART) regimen for persons living with HIV (PWH), comprising over 80% of such treatments. To broaden treatment options and improve therapeutic effectiveness, Ainuovirine (ANV), a new NNRTI, was authorized for ART in 2021. Nevertheless, the clinical efficacy of ANV and its impact on blood biochemical markers remain somewhat underexplored. This study seeks to evaluate ANV's clinical performance in ART and its influence on relevant treatment parameters. A retrospective analysis was performed on 208 patients treated with an ANV-based regimen from July 2021 to July 2023, monitoring indicator changes from baseline to week 24. The primary endpoint was the proportion of participants achieving HIV-1 RNA levels of less than 50 copies/mL by week 24. Secondary endpoints involved assessing variations in CD4 + T cell counts and blood biochemical markers from baseline. These outcomes were also compared with data from 241 patients treated with an Efavirenz (EFV)-based regimen in the same time frame. The findings suggest that the ANV-based regimen is as effective as the EFV-based regimen in viral suppression ( p > .05) and offers superior improvements in lipid profiles, liver function, and immune system indicators, alongside fewer adverse reactions. These results affirm ANV's efficacy and safety as an antiretroviral therapy option, offering Acquired Immune Deficiency Syndrome patients a wider array of treatment possibilities and the potential for better treatment outcomes.

Background: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with human immunodeficiency virus (HIV)-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400 mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among men who have sex with men (MSM) who have been diagnosed with HIV., Methods: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV (400 mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/mL) at 48 weeks per US Food and Drug Administration Snapshot analysis., Results: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression, and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (P < .001), respectively, discontinued treatment because of adverse effects, death, or lost to follow-up. The median increase of CD4 count was 181 and 223 cells/μL (P = .020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < .001)., Conclusions: BIC/FTC/TAF was more efficacious and safer than EFV (400 mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China., Competing Interests: Potential conflicts of interest. L. D. served on the advisory boards of Gilead Sciences and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia., Methods: Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed., Results: Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/μL, CD8: 709 [547-893] cells/μL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits., Conclusion: We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Immediate start of antiretroviral treatment (ART) among non-hospitalized outpatient children living with HIV may improve or worsen clinical outcomes due to immune reconstitution., Objective: Role of immediate versus post-stabilization start of antiretroviral treatment in children and youths living with HIV on CD4 count and viral load suppression., Methods: This was a single blinded, randomized controlled trial conducted on outpatients attending a tertiary care hospital associated HIV clinic in North India. We enrolled ART-naive children and youths living with HIV aged 18 months to 21 years in a 1:1 ratio. Block randomization was done using computerized software. Children and youths living with HIV were either started with ART on diagnosis immediately within 24 h (Group A) or post stabilization at 2 weeks (Group B) as per National AIDS Control Organization (NACO) India guidelines. Both groups were comparable for baseline characteristics., Results: There was no significant difference seen in CD4 counts between two groups at 6 months follow up. CD4 count increased significantly in immediate group but not in post-stabilization group at 6 months. No significant changes/differences was seen in WHO clinical staging or anthropometry; one patient developed tuberculosis in both groups. Viral load at 6 months in both the groups did not differ significantly., Conclusion: Immediate ART in children and youths living with HIV results in significant increase in CD4 count at 6 months follow up exemplifying immunological response to ART., 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.

Objective: To investigate the association of age at antiretroviral therapy (ART) initiation with CD4 +  : CD8 + T-cell ratio in virally suppressed people with HIV on long-term ART, and to characterize potential CD4 +  : CD8 + ratio recovery in this population by age., Design: A longitudinal study of people attending an HIV clinic at the Royal Free Hospital NHS Trust, London, who initiated ART between 2001 and 2015, and achieved and maintained HIV-1 viral suppression (viral load <1,000 copies/ml). The association of age group at ART initiation with CD4 +  : CD8 + ratio at 5 and 10 years was assessed., Methods: Multivariable linear regression was used to investigate the relationship between age at ART initiation and log CD4 +  : CD8 + ratio, adjusting for demographic factors (gender/HIV transmission route, ethnicity), baseline CD4 + count and calendar year., Results: The sample included 1859 people aged 20-78 (75% men, 56% white ethnicity). Overall, median CD4 +  : CD8 + T-cell ratio increased from 0.24 at baseline to 0.77 at year 5 and 0.88 at year 10. Ratios increased among all age groups in unadjusted and adjusted models but increased less among older ages (baseline ages 60-69 and 70-79). Median ratios at year 5 were 0.85, 0.80, 0.72, 0.76, 0.6, and 0.44, respectively, among people aged 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years at baseline., Conclusion: In a virally suppressed London population, age had a substantial impact on CD4 +  : CD8 + ratio recovery, especially for those starting ART after age 60 years. Results may indicate the level of CD4 +  : CD8 + ratio recovery possible in an HIV-positive, virally suppressed, aging population., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. This study included newly diagnosed HIV adults from Tianjin, China, between 2016 and 2022. Our primary outcome was loss to follow-up (LTFU) at 12 months after enrollment. The secondary outcome was 12-month virological failure. The association between rapid ART and LTFU, as well as virological failure, was assessed via Cox regression and logistic regression. A total of 896 (19.1%) of 4688 participants received ART ≤7 days postdiagnosis. The rate of rapid ART has increased from 7.5% in 2016 to 33.3% by 2022. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed group. The rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU [adjusted hazard ratio: 0.65, 95% confidence intervals (CI): 0.44-0.96] and virological failure (adjusted odds ratio: 0.35, 95% CI: 0.12-0.80). The real-world data indicated that rapid ART is practicable and beneficial for Chinese people with HIV, providing evidence for its widespread implementation and scaling up.

Objective: The objective of the study was to determine the effect of probiotics and of probiotic-fermented foods on CD4 T-cell count, viral load, anaemia and body mass index (BMI) among people living with HIV (PLHIV)., Methods: In this article, we systematically reviewed the evidence on the influence of probiotic supplementation on CD4 lymphocyte count, viral load and anaemia among PLHIV on highly active antiretroviral therapy (HAART) and those who were HAART-naive. Medical literature databases identified randomised trials and pre-post studies of probiotic supplementation and HIV-related outcomes, and random effects meta-analysis was conducted., Results: The preponderance of the evidence suggests that probiotic supplementation only improved CD4 lymphocyte count modestly, with quantitatively greater impact among individuals who were HAART-naive compared to HAART-experienced individuals. Probiotic supplementation improved CD4 lymphocyte count by 53 cells/mm 3 (95% CI: 22 to 85) from 18 studies. Probiotic supplementation however reduced haemoglobin concentration by -2.1 g/L (95% CI: -4.0 to -0.2). Although viral load remain unchanged in HAART-experienced participants following probiotic supplementation, HAART-naïve participants saw a decrease in viral load. There were too few studies on the impact of probiotic supplementation on viral load (N = 1)., Conclusion: Probiotic supplementation resulted in a modest increase in CD4 lymphocyte count among HAART-naive individuals with no significant change observed among HAART-experienced ones. Viral load and haemoglobin concentration also remained unchanged following probiotic supplementation. Further rigorous and well-powered studies may evaluate the effect of probiotic supplementation on important clinical outcomes among PLHIV on HAART., (© 2023 John Wiley & Sons Ltd.)

HIV epidemics still exist as a major global public health burden, especially in middle- and low-income countries. Given the lack of approved vaccines, antiretroviral therapy (ART) remains the primary approach to reduce the mortality and morbidity linked to this disease. Effective treatment for HIV-1 requires the simultaneous administration of multiple drugs. However, the virus can show resistance to antiretroviral drugs, resulting in treatment failure. Therefore, this study focused on assessing the prevalence of mutations within the Indian HIV-positive population. After assessing the data, we intended to identify the most effective highly active ART (HAART) regimens for individuals with drug-resistant variants. Furthermore, our analysis revealed a spectrum of HIV mutations, with varying effects on protein stability. The significance of this analysis lies in its potential to optimize HAART selection for HIV-positive individuals by accounting for both prevalence and stability-altering mutations. By considering mutation effects on protein stability, we can modify treatment regimens, increasing the likelihood of therapy success and diminishing the risk of resistance. Moreover, this study contributes to the broader field of drug repurposing, offering insights into the rational design of antiretroviral therapies., (Copyright: © 2024 Permanyer.)

We estimate the effectiveness of antiretroviral therapy (ART) among individuals receiving HIV care in Rio de Janeiro, Brazil. Adults (18y+) initiating ART between Jan/2008 and Dec/2018 (follow-up through Dec/2020) were included. First-line ART (two nucleoside reverse transcriptase inhibitors plus one antiretroviral from another class) was categorized into four categories: non-nucleoside reverse transcriptase inhibitor/NNRTI-based, protease inhibitor/PI-based, integrase strand transfer inhibitor/INSTI-based, and single-tablet regimen (STR, Tenofovir 300mg + Lamivudine 300mg + Efavirenz 600mg). Effectiveness (viral load ≤50 copies/µL) was evaluated at 6(3-9) and 12(9-15) months from ART initiation. Bayesian logistic regression models were used to quantify the association between exposure and outcomes while accounting for missing data. Overall, 1863(57%), 652(19.9%), 412(12.6%), and 342(10.5%) individuals used, respectively, NNRTI-based, PI-based, INSTI-based regimens, and STR. Compared to NNRTIs, the odds of viral suppression with INSTI-based regimens was 76% higher (adjusted OR:1.76, 95%CI:1.23-2.51) at six months but no higher at 12 months. Older age, higher education, CD4 count ≥500 cells/mm 3 and viral load <100,000 copies/µL at ART initiation increased the odds of viral suppression. Viral suppression at six months was the strongest predictor of viral suppression at 12 months. These results highlight population groups that could benefit from close monitoring during the first year of ART.

Background: 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., Objective: 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., Study Design: 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., Results: 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., Conclusion: 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., (Published by Elsevier Inc.)

Background: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system., Methods: A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48., Results: Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10)., Conclusions: This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight., Competing Interests: Potential conflicts of interest. S. L. L. reports a research grant from Merck & Co to the University at Buffalo (UB) with a subcontract from UB to the author's university. E. S. D. reports grants or contracts from Gilead Sciences, Merck, and ViiV Healthcare and consulting fees from Gilead Sciences, Merck, ViiV Healthcare, and Theratechnologies. P. W. H. reports a research grant to institution from Gilead Sciences; donation of drug for NIH-sponsored trial from Merck; consulting fees to author from ViiV Healthcare and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead Sciences and ViiV Healthcare; and participation on a data and safety monitoring board (DSMB) or advisory board with Longeveron. C. M. M. reports grants from NIH/NINDS paid to institution; royalties from Wolters Kluwer to author; consulting fees to author for review of patient charts for law firms; payment for course directorship and continuing medical education lectures at the American Academy of Neurology annual meeting and payment or honoraria for manuscript writing for Medlink Neurology; and a paid role on editorial boards for Medlink Neurology, Frontiers in Neurology. T. B. C. reports grants or contracts from NIH, consulting fees from ViiV Healthcare, and payment to institution for expert testimony from Sidley Austin, LLP. Q. M. reports consulting fees paid to author from Change Healthcare and a role as Toxicology Division chair-elect for the American Society for Pharmacology and Experimental Therapeutics. S. Sw. reports grants or contracts from Gilead Sciences for retrospective chart review (not related to this project) and Real World PrEP data and from Janssen Therapeutics for an HIV vaccine study; consulting fees to author from ViiV Healthcare, Gilead Sciences, and Moderna; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ViiV Healthcare and Gilead Sciences. B. J. C. M. reports research support from Astra Zeneca. G. D. M. reports participation on a DSMB or advisory board. T. M. reports stock or stock options and other financial or nonfinancial interests from Science 37 (recent employer). A. L. G. reports contract testing to institution from Abbott, Cepheid, Novavax, Pfizer, Janssen Therapeutics, and Hologic and research support from the Bill & Melinda Gates Foundation and Gilead Sciences, outside of the described work. B. H. reports stock or stock options as an employee of ViiV Healthcare. S. Sp. reports grants from the NIH (from NIMH, NINDS, and NIDA), honorarium from the IAS-USA for lectures, and honorarium from academic institutions for grand rounds and other invited talks. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine the characteristics of people with HIV (PWH) who prefer remaining on daily oral antiretroviral therapy (ART), rather than switching to long-acting ART (LA-ART)., Design: Building upon a discrete choice experiment (DCE), we examined characteristics of individuals who always selected their current daily oral tablet regimen over either of two hypothetical LA-ART options presented in a series of 17 choice tasks., Methods: We used LASSO to select sociodemographic, HIV-related, and other health-related predictors of preferring current therapy over LA-ART, and logistic regression to measure the associations with those characteristics., Results: Among 700 PWH in Washington State and Atlanta, Georgia, 11% of participants ( n  = 74) chose their current daily treatment over LA-ART in all DCE choice tasks. We found that people with lower educational attainment, good adherence, more aversion to injections, and who participated from Atlanta to be more likely to prefer their current daily regimen over LA-ART., Conclusions: Gaps in ART uptake and adherence remain, and emerging LA-ART treatments show promise to address these challenges and help a larger portion of PWH to achieve viral suppression, but preferences for these new treatments are understudied. Our results show that certain drawbacks of LA-ART may help to maintain demand for daily oral tablets, especially for PWH with certain characteristics. Some of these characteristics (lower educational attainment and Atlanta participation) were also associated with a lack of viral suppression. Future research should focus on overcoming barriers that impact preferences for LA-ART among those patients who could benefit most from this innovation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Protocol adherence may influence measured treatment effectiveness in randomized controlled trials. Using data from a multicenter trial (Europe and the Americas, 2002-2009) of children with human immunodeficiency virus type 1 who had been randomized to receive initial protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral therapy regimens, we generated time-to-event intention-to-treat (ITT) estimates of treatment effectiveness, applied inverse-probability-of-censoring weights to generate per-protocol efficacy estimates, and compared shifts from ITT to per-protocol estimates across and within treatment arms. In ITT analyses, 263 participants experienced 4-year treatment failure probabilities of 41.3% for PIs and 39.5% for NNRTIs (risk difference = 1.8% (95% confidence interval (CI): -10.1, 13.7); hazard ratio = 1.09 (95% CI: 0.74, 1.60)). In per-protocol analyses, failure probabilities were 35.6% for PIs and 29.2% for NNRTIs (risk difference = 6.4% (95% CI: -6.7, 19.4); hazard ratio = 1.30 (95% CI: 0.80, 2.12)). Within-arm shifts in failure probabilities from ITT to per-protocol analyses were 5.7% for PIs and 10.3% for NNRTIs. Protocol nonadherence was nondifferential across arms, suggesting that possibly better NNRTI efficacy may have been masked by differences in within-arm shifts deriving from differential regimen forgiveness, residual confounding, or chance. A per-protocol approach using inverse-probability-of-censoring weights facilitated evaluation of relationships among adherence, efficacy, and forgiveness applicable to pediatric oral antiretroviral regimens., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: G. D. received honoraria as consultant, lecturer, or advisory board member from Gilead, ViiV Healthcare, Janssens and MSD. All other authors declare no conflict of interests. No funding was obtained for this study.

Background & Objective: Human Immunodeficiency Virus (HIV) remains one of the world's most serious health challenges. The development of therapeutic regimens has significantly increased survival and reduced HIV-associated morbidities in HIV-infected individuals. However, some people living with HIV may not respond as expected, resulting in treatment failure. The objective of this study is to identify and characterize, by immunological (T-cell CD4) and virological (viral load) parameters, HIV infected patients with therapeutic failure in Morocco., Methods: Prospective cross-sectional studies were conducted over a 5-years period (between January 2015 and December 2019) at the referral center of Ibn Zohr Hospital, Marrakech, Morocco. A total, of 1088 HIV-infected patients diagnosed by the rapid test (Immunochromatography) in addition to Western Blot analysis, was recruited. All patients were under the antiretroviral therapy (ART) for at least six months and followed every six months. Sociodemographic, clinical, and biological data as well as information on patient adherence were collected., Results: Out of 1088 patients, 92.46% were under treatment based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) including 26.20% first line first intention and 66.26% first line second intention, and 7.54% of patients on a protease inhibitor (PI) therapy. Regarding the immunological and virological status, 76% of HIV-infected patients had a CD4 count > 200 cells/µl and 24% had a CD4 count < 200 cells / µl, while 69.5% had an undetectable viral load and 30.05% had a detectable viral load (including 11.86% with viral load < 1000 copies / ml and 18.20% viral load > 1000 copies / ml) (P-values < 0.05)., Conclusion: In our study, we showed a therapeutic failure rate of 18.2% in HIV-infected patients under treatment in Marrakech region. These failures were mainly related to poor adherence and low CD4+ rates at the initiation of treatment. We concluded that immunological monitoring alone is insufficient to predict virological suppression and therapeutic success. Consequently, we recommend the HIV plasma viral load test be accessible as a routine exam., Competing Interests: The authors declare no conflict of interest., (© 2023 Echchakery M et al.)

Background: Pretreatment HIV drug resistance (PHDR) has emerged after scaling-up access to antiretroviral therapy (ART). This study aimed to compare long-term virological and immunological outcomes between HIV-positive individuals with and without PHDR., Methods: An observational cohort study was conducted in HIV-positive individuals who had a genotypic resistance test performed prior to ART initiation., Results: Of 335 participants, 39 were in the PHDR group and 296 were in the control group. ART regimen in PHDR group was adjusted at 6-10 weeks after ART initiation when results of baseline genotypic resistance test were available. Proportions of participants with undetectable viral load were significantly lower in PHDR group at 6 and 12 months (46.2% vs 79.4% ( p < .001) and 74.4% vs 90.5% ( p = .003), respectively). These virological responses became similar between two groups ( p > .05) from 18 through 60 months. Mean change of CD4 counts of PHDR group was significantly lower only at 6 months (+59 vs + 81 cells/mm 3 ( p = .012); these immunological responses were similar between two groups from 12 through 60 months., Conclusion: Early virological response was lower in HIV-positive participants with PHDR compared to participants without PHDR. Subsequent adjustment of ART according to pretreatment genotypic resistance has contributed to the long-term virological and immunological success that is similar to participants without PHDR.

Suboptimal adherence to antiretroviral therapy (ART) in people with HIV, even during sustained viral suppression, is associated with persistent inflammation, immune activation, and coagulopathy. Persistently low CD4-CD8 Ratio has been also associated with residual inflammation, is a good predictor of increased risk of death and more widely available than inflammatory biomarkers. We tested the hypothesis that the CD4-CD8 Ratio is associated with ART adherence during periods of complete viral suppression. We used the Medication Possession Ratio based in pharmacy registries as measure of adherence and time-varying, routine care CD4 and CD8 measurements as outcome. We used a linear mixed model for longitudinal data, including fixed effects for sex, age, education, date of ART initiation, AIDS-related conditions, and baseline CD4 to model the outcome. In 988 adults with a median follow-up of 4.13 years, higher ART adherence was independently associated with a modest increase in CD4-CD8. For each increasing percentage point in adherence, the CD4-CD8 Ratio increased 0.000857 (95% confidence interval [CI] -0.000494 to 0.002209, p  = .213731) in the first year after achieving viral suppression; 0.001057 (95% CI 0.000262-0.001853, p  = .009160) in years 1 to 3; 0.000323 (95% CI -0.000448 to 0.001095, p  = .411441) in years 3 to 5; and 0.000850 (95% CI 0.000272-0.001429, p  = .003946) 5-10 years after achieving viral suppression. The magnitude of the effect of adherence over CD4-CD8 Ratios varied over time and by baseline CD4 count, with increasing adherence having a larger effect early after ART initiation in people with higher baseline CD4 (>500 cells/μL) and in later years in people with lower baseline CD4 count (≥200 cells/μL). Our findings expand on previous evidence suggesting that the benefits of optimal adherence to modern ART regimens goes beyond maintaining viral suppression. These results highlight the importance of including objective measurements of adherence as part of routine care, even in patients with complete HIV suppression over long-term follow-up.

Objective: Despite improved access to antiretroviral therapy (ART) for people with HIV (PWH), HIV continues to contribute considerably to morbidity and mortality. Increasingly, advanced HIV disease (AHD) is found among PWH who are ART-experienced., Design: Using a multi-state model we examined associations between engagement with care and AHD on ART in South Africa., Methods: Using data from IeDEA Southern Africa, we included PWH from South Africa, initiating ART from 2004 to 2017 aged more than 5 years with a CD4+ cell count at ART start and at least one subsequent measure. We defined a gap as no visit for at least 18 months. Five states were defined: 'AHD on ART' (CD4+ cell count <200 cells/μl), 'Clinically Stable on ART' (CD4+ cell count ≥200 or if no CD4+ cell count, viral load <1000 copies/ml), 'Early Gap' (commencing ≤18 months from ART start), 'Late Gap' (commencing >18 months from ART start) and 'Death'., Results: Among 32 452 PWH, men and those aged 15-25 years were more likely to progress to unfavourable states. Later years of ART start were associated with a lower probability of transitioning from AHD to clinically stable, increasing the risk of death following AHD. In stratified analyses, those starting ART with AHD in later years were more likely to re-engage in care with AHD following a gap and to die following AHD on ART., Conclusion: In more recent years, those with AHD on ART were more likely to die, and AHD at re-engagement in care increased. To further reduce HIV-related mortality, efforts to address the challenges facing these more vulnerable patients are needed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The study investigated the durability of switched therapy and factors associated with the viral rebound among patients on second-line antiretroviral therapy (ART) in Uganda., Design: A retrospective dynamic cohort of adults initiated on second-line ART after virological failure to first-line ART., Methods: Patients on second-line treatment for at least 6 months between 2007 and 2017 were included. Patients were followed, until they experienced a viral rebound (viral load ≥200 copies/ml). Cumulative probability of viral rebounds and factors associated with viral rebound were determined using Kaplan-Meier methods and Cox proportional hazard models., Results: One thousand, one hundred and one participants were enrolled of which 64% were women, the median age was 37 years [interquartile range (IQR) 31-43]. The preswitch median CD4 + cell count and viral load were 128 cells/μl (IQR 58-244) and 45 978 copies/ml (IQR 13 827-139 583), respectively. During the 4190.37 person-years, the incidence rate of viral rebound was 83.29 [95% confidence interval (CI) 74.99-92.49] per 1000 person-years. The probability of viral rebound at 5 and 10 years was 0.29 (95% CI 0.26-0.32) and 0.62 (95% CI 0.55-0.69), respectively. The median rebound-free survival was 8.7 years. Young adults (18-24 years) [adjusted hazard ratio (aHR) 2.49, 95% CI 1.32-4.67], preswitch viral load at least 100 000 copies/ml (aHR 1.53, 95% CI 1.22-1.92), and atazanavir/ritonavir (ATV/r)-based second-line (aHR 1.73, 95% CI 1.29-2.32) were associated with an increased risk of viral rebound., Conclusion: Switched therapies are durable for 8 years after failure of recommended regimens. A high preswitch viral load, ATV/r-based regimens, and young adulthood are risk factors for viral rebound, which underscores the need for more durable regimens and differentiated care services., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Human Immunodeficiency Virus infection leads to the impairment of immune system function. Even long-term antiretroviral therapy uncommonly leads to the normalization of CD4 count and CD4:CD8 ratio. The aim of this study was to evaluate possible clinical biomarkers which may be related to CD4 and CD4:CD8 ratio recovery among HIV-infected patients with long-term antiretroviral therapy. The study included 68 HIV-infected patients undergoing sustained antiretroviral treatment for a minimum of 5 years. Clinical biomarkers such as age, gender, advancement of HIV infection, coinfections, comorbidities and applied ART regimens were analyzed in relation to the rates of CD4 and CD4:CD8 increase and normalization rates. The results showed that higher rates of CD4 normalization are associated with younger age ( p = 0.034), higher CD4 count ( p = 0.034) and starting the therapy during acute HIV infection ( p = 0.012). Higher rates of CD4:CD8 ratio normalization are correlated with higher CD4 cell count ( p = 0.022), high HIV viral load ( p = 0.006) and acute HIV infection ( p = 0.013). We did not observe statistically significant differences in CD4 recovery depending on gender, HCV/HBV coinfections, comorbidities and opportunistic infections. The obtained results advocate for current recommendations of introducing antiretroviral therapy as soon as possible, preferably during acute HIV infection, since it increases the chances of sufficient immune reconstruction.

Objectives: To determine the factors associated with poor outcomes among people living with HIV (PLHIV) started on anti- retroviral therapy before and after implementation of "Test and treat" program in 18 facilities in Coastal Kenya., Methods: A retrospective cohort study design was used to study PLHIV aged > 15 years and started on ART in the periods of April to August 2016, and April to August 2017, then followed up for 24 months. Primary outcome was retention defined as being alive and on ARVs after 24 months. Death and loss to follow-up were considered as poor outcomes. Kaplan-Meier survival methods were used to describe time to primary outcome. Cox proportional regression analysis was used to determine factors associated with poor outcomes., Results: 86 patients (470 before test and treat, and 316 after test and treat cohorts) were enrolled. Overall, the median [IQR] age was 39.3 [32.5-47.5] years and 539 (69%) were female. After 24 months, retention rates for the before (68%) and after (64%) test and start groups were similar (absolute difference: -4.0%, 95%CI: -11-3.1, P = 0.27). There were 240(31%, 95%CI 27 to 34%) PLHIV with poor outcomes, 102 (32%) and 138 (29%) occurred among the test and treat group, and delayed treatment patients respectively. In multivariable regression model, test and treat had no significant effect on risk of poor outcomes (aHR = 1.17, 95%CI 0.89-1.54). Increasing age (aHR = 0.98, 95%CI 0.97-0.99), formal employment (aHR = 0.42, 95%CI 0.23-0.76) and not being employed (aHR = 0.53, 95%CI 0.34-0.81) were negatively associated with poor outcomes. The risk of poor outcomes was higher among males compared to female patients (aHR = 1.37, 95%CI 1.03-1.82) and among divorced/separated patients compared to the married (aHR = 1.44, 95%CI 1.04-1.99)., Conclusion: Retention patterns for the "test and treat" cohort were comparable to those who started ART before "test and treat". Patients who are males, young, divorced/separated, with poor socio-economic status had higher risks for poor clinical outcomes. Interventions targeting PLHIV who are young, male and economically disadvantaged provide an opportunity to improve the long-term outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: While combination antiretroviral therapy (cART) has dramatically increased the life expectancy of people with HIV (PWH), nearly 50% develop HIV-associated neurocognitive disorders. This may be due to previously uncontrolled HIV viral replication, immune activation maintained by residual viral replication or activation from other sources, or cART-associated neurotoxicity. The aim of this study was to determine the effect of cART on cognition and neuroimaging biomarkers in PWH before and after initiation of cART compared with that in HIV-negative controls (HCs) and HIV elite controllers (ECs) who remain untreated., Methods: We recruited 3 groups of participants from the University of Rochester, McGovern Medical School, and SUNY Upstate Medical University: (1) ART treatment-naive PWH; (2) age-matched HCs; and (3) ECs. Participants underwent brain MRI and clinical and neuropsychological assessments at baseline, 1 year, and 2 years. PWH were also assessed 12 weeks after initiating cART. Volumetric analysis and fractal dimensionality (FD) were calculated for cortical and subcortical regions. Mixed effect regressions examined the effect of group and imaging variables on cognition., Results: We enrolled 47 PWH, 58 HCs, and 10 ECs. At baseline, PWH had worse cognition and lower cortical volumes than HCs. Cognition improved after initiation of cART and remained stable over time. Greater cortical thickness was associated with better cognition at baseline; greater FD of parietal, temporal, and occipital lobes was associated with better cognition at baseline and longitudinally. At baseline, ECs had worse cognition, lower cortical thickness, and lower FD in all 4 lobes and caudate than PWH and HCs. Greater cortical thickness, hippocampal volumes, and FD of frontal, temporal, and occipital lobes were associated with better cognition longitudinally., Discussion: Initiation of cART in PWH is associated with improvement in brain structure and cognition. However, significant differences persist over time when compared with HCs. Similar trends in ECs suggest that results are due to HIV infection rather than treatment. Stronger associations between cognition and FD suggest this imaging metric may be a more sensitive marker of neuronal injury than cortical thickness and volumetric measures., (© 2022 American Academy of Neurology.)

Background: Human immunodeficiency virus (HIV) contributes significantly to morbidity and mortality in South Africa. Pneumonia and opportunistic infections remain a major cause for hospital admission among those living with HIV, even in the era of the widespread availability of antiretroviral therapy., Methods: In this retrospective cohort study, the records of patients admitted with HIV and severe pneumonia, requiring high care/intensive care admission, during a period of 12 months (February 2018 to January 2019) were reviewed. Demographic details, antiretroviral use, HIV viral load, CD4 count, sputum culture results and radiological imaging of patients were recorded. Data was analysed to determine variables associated with mortality., Results: One hundred and seventeen patient records were reviewed for this study. The patients were young (mean age 38.3 years), had advanced disease with low CD4 counts (mean 120.2 cells/mm 3 ) and high HIV viral loads (mean 594,973.7 copies/mL). Only 36.9% (42/117) were on highly active antiretroviral therapy (HAART) on presentation to the hospital. Mycobacterium tuberculosis (M. tuberculosis) was found to be the cause for pneumonia in 35% (41/117), whilst Pneumocystis jirovecii (P. jirovecii) was found in 21.4% (25/117). Bacterial pneumonia was the cause in 17.1% (20/117) of patients while no specific aetiology was found in 26.6% (31/117) of patients in the cohort. Mortality among the cohort studied was high (40.1%) and the average length of stay in hospital in excess of two weeks. The need for ICU admission, ventilation and CMV viremia was associated with increased mortality. Chest X-ray findings did not correlate with the aetiology of pneumonia, but multiple B-lines on lung ultrasound correlated with P. jirovecii as an aetiology and there was a signal that pleural effusion with fibrin stranding predicts tuberculosis., Conclusions: Patients studied presented with advanced HIV and were often naïve to antiretroviral therapy. Mortality in this cohort of young patients was high, which emphasis the need for earlier diagnosis and treatment of HIV at a primary care level. Lung ultrasound may have clinical utility in the management of patients with HIV and pneumonia, particularly to diagnose P. jirovecii as an aetiology., (© 2022. The Author(s).)

Background: Hepatotoxicity due to highly active antiretroviral therapy (HAART) has gained prominent attention since it can be affected by many factors. The aim of this study was to determine the prevalence of hepatotoxicity and related risk factors of severe hepatotoxicity following HAART initiation., Methods: A total of 100 drug-naive patients aged between 18 and 61 years were recruited. They were put on Tenofovir/Lamivudine/Efavirenz [TDF/3TC/EFV] (64), Zidovudine/ Lamivudine/Efavirenz [AZT/3TC/EFV] (22), and Zidovudine/Lamivudine/Nevirapine AZT/3TC/NVP (14) and monitored for 6months and blood samples drawn.Alanine aminotransferases (ALT), aspartate aminotransferases (AST), and alkaline phosphatase (ALP) wereanalyzed by enzymatic methods and used to classify levels of hepatotoxicity., Results: A total of 37(37%) and 49(49%) patients presented with hepatotoxicity while 15% and 28% had severe hepatotoxicity at 4 and 24 weeks respectively. Serum levels of all enzymes increased significantly (p = 0.001) with increased treatment duration. Univariate analysis revealed that the risk factor of developing severe hepatotoxicity was significantly greater in patients < 30years (p = 0.02), males(p = 0.04), low BMI (p = 0.02), low monthly income (p = 0.01) earners, and patients on AZT + 3TC + NVP regimen (p = 0.01). While multivariate analysis at p < 0.09 showed that age 30-40 years, low BMI, low monthly income, and the use of AZT + 3TC + NVP regimen were independent risk factors., Conclusions: Low BMI, age group of 30-40years, low monthly income, and the use of AZT + 3TC + NVP regimen identified as risk factors for the development of severe hepatotoxicity should be considered as an important strategy by clinicians in preventing the hepatotoxicity., (© 2022. The Author(s).)

Background: While increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial., Methods: We selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, and A5257 who had achieved viral suppression at year 2. We examined the effect of CD8+ T cell counts and CD4/CD8 at year 2 on the probability of AIDS and serious non-AIDS events in years 3-7. We used inverse probability weighting methods to address informative censoring, combined with multivariable logistic regression models., Findings: We analyzed 5133 participants with a median age of 38 years; 959 (19%) were female, pre-ART median CD4 counts were 249 (Q1-Q3 91-372) cell/µL. Compared to participants with CD8 counts between 500/µL and 1499/µL, those with >1500/µL had a higher risk of clinical events during years 3-7 (aOR 1.75; 95%CI 1.33-2.32). CD4/CD8 ratio was not predictive of greater risk of events through year 7. Additional analyses revealed consistent CD8 count effect sizes for the risk of AIDS events and noninfectious non-AIDS events, but opposite effects for the risk of severe infections, which were more frequent among individuals with CD8 counts <500/µL (aOR 1.70; 95%CI 1.09-2.65)., Interpretation: The results of this analysis with pooled data from clinical trials support the value of the CD8 count as a predictor of clinical progression. People with very high CD8 counts during suppressive ART might benefit from closer monitoring and may be a target population for novel interventions., Funding: This research was supported by NIH/NIAID awards UM1 AI068634, UM1 AI068636, and UM1 AI106701 and Carlos III Health Institute and FEDER funds (BA21/00017 and BA21/00022)., Competing Interests: Declaration of interests Dr. Serrano-Villar reports grants from MSD, grants and personal fees from Gilead, non-financial support from ViiV, outside the submitted work; Dr. Hunt reports grants and personal fees from Gilead, non-financial support from Merck, personal fees from Viiv, personal fees from Biotron, outside the submitted work; Dr. Moreno reports grants, personal fees and non-financial support from Gilead Sciences, personal fees from Janssen Pharmaceuticals, grants, personal fees and non-financial support from Viiv Healthcare, grants, personal fees and non-financial support from MSD, outside the submitted work; Dr. Bosch reports grants from NIH/NIAID, during the conduct of the study; grants from NIH/NIAID, outside the submitted work., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4 + T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4 + T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4 + T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders ( p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits ( p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels ( p < 0.01), and low circulating RBP4 concentrations were related to a low CD4 + T-cell gain ( p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4 + T cells at 144 weeks ( p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.

Objective: The main objective of this study was to describe the perceived quality of life (QoL) in patients living with AIDS (PLWA) and their chosen coping strategies in a cohort of individuals managed with HAART., Methods: This is a prospective cohort study conducted at the Medication Dispensing Unit of a university hospital (MDU-UH) located in southeastern Brazil. Study population comprised HIV/AIDS patients starting antiretroviral treatment at MDU. The final sample comprised 99 participants. Patients were followed up for 24 months from their recruitment. We used a face-to-face questionnaire to determine sociodemographic and behavioural variables. Quality of life (QoL) and coping strategies (CS) were measured through validated instruments., Results: Regarding the QoL dimensions, the general perception of QoL among these participants was considered good. Regarding CS, the adherent patients scored higher than the nonadherents., Conclusions: The present study revealed that the perceived QoL can be maintained in individuals treated for HIV/AIDS. There is an association between high score of coping strategies and adherence to HAART., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Patricia de Oliveira França et al.)

Purpose: The incomplete immune reconstitution is a complex phenomenon among human immunodeficiency virus (HIV)-infected patients despite the fact that they have achieved persistent viral suppression under the combined antiretroviral therapy. This study aims to screen and verify the immunological characteristics and underlying mechanisms of immunological non-responders (INRs)., Methods: The RNA-seq and the differentially expressed genes (DEGs) analysis were used to explore potential characteristics among INRs. Gene Ontology (GO) enrichment, ingenuity pathway analysis (IPA) analysis, Gene set enrichment analysis (GSEA) analysis, and the weighted gene co-expression network analysis (WGCNA) were used to explore the potential mechanism. The transcriptional meta-analysis was used to analyze the external efficiency., Results: The RNA-seq identified 316 DEGs among INRs. The interferon signaling pathway was enriched via GO and IPA analysis among DEGs. The combined GSEA and WGCNA analysis confirmed that the IFN response was more correlated with INR. Furthermore, IFI27 (IFN-α Inducible Protein 27, also known as ISG12) was chosen based on combined DEG analysis, WGCNA analysis, and the transcriptional meta-analysis conducted on other published datasets about INRs. The expression of IFI27 was significantly negatively correlated with the CD4+ T-cell counts of PLWH, and the predictive efficiency of IFI27 level in distinguishing PLWH with poor immune recovery was also with significant power (AUC = 0.848)., Conclusion: The enhanced expression of IFI27 and the IFN response pathway are among the important immunological characteristics of INRs and exhibited promising efficiency as biomarkers for CD4 + T-cell recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Lin, Lu, Li, Han, Qiu, Li, Li, Song, Cao and Li.)

Objective: We investigated prevalence and predictors of glucose metabolism disorders (GMDs) among People Living with HIV (PLWH) on efavirenz- and atazanavir/ritonavir-based combination antiretroviral therapy (cART)., Methods: This cross-sectional study involved adult PLWH on efavirenz- (n = 240) and atazanavir/ritonavir-based (n = 111) cART. The prevalence of GMDs was determined by fasting serum glucose, insulin, and homeostasis model assessment. A logistic regression model was used to determine predictors., Results: The overall prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0-32.6%] s, with 31.1% (75/240) [95% CI 25.4-37.5%] for efavirenz-based and 19.8% (22/111) [95% CI 12.9-28.5%)] for atazanavir/ritonavir-based cART group. The prevalence of impaired fasting glycemia was significantly higher (p = 0.026) in the efavirenz- [(15.4%) (37/240); 95%CI (11.1-20.6%)] than atazanavir/ritonavir-based [(7.2%) (8/111), (95%CI (3.2-13.7%)] cART. However, no significant difference was observed in the prevalence of diabetes mellitus and insulin resistance between the two regimens. Age ≥46 years old and specific type of ARV contained in cART, such as TDF, were independent predictors of GMD in both groups. Whereas the male gender and BMI category were predictors of GMDs among EFV-based cART group, AZT- and ABC- containing regimens and triglyceride levels were predictors in the ATV/r-based group., Conclusions: GMDs were highly prevalent among adults on EFV- than ATV/r-based cARTs. Age ≥46 years and TDF-containing cARTs are common predictors in both regimens. Close monitoring for impaired fasting glucose during long-term EFV-based cART is recommended for early diagnosis of type-2 diabetes and management., Competing Interests: The authors have declared that no competing interests exist.

Background: Human immunodeficiency virus (HIV) infection induces epigenetic age acceleration (EAA), but it remains unclear whether epigenetic aging continues to accelerate during successful antiretroviral therapy (ART) and prolonged virological suppression., Methods: We longitudinally analyzed 63 long-term aviremic HIV-infected adults. Using blood DNA methylation patterns, we calculated EAA measures based on 3 epigenetic clocks (Horvath's clock, PhenoAge, and GrimAge). We recorded the emergence of serious AIDS-related and non-AIDS-related events throughout the study to assess its association with EAA., Results: All participants were on stable ART and were virologically suppressed. After 4 years of follow-up, PhenoAge-EAA and GrimAge-EAA showed no differences, whereas Horvath-EAA slightly decreased (median difference, -0.53 years; P = .015). Longitudinal changes in EAA measures were independent of changes in CD4 cell counts, the ART regimen, or other HIV-related factors. Nineteen percent of participants experienced a serious clinical event during the study. Horvath-EAA was significantly higher at baseline in participants with clinical events (P = .027). After adjusting for confounders, we found a trend toward an association of higher levels of all EAA measures at baseline with serious clinical events., Conclusions: Epigenetic aging did not accelerate in long-term aviremic HIV-infected adults after 4 years of successful ART. EAA measures deserve further study as potential tools for predicting clinical events., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In 2010, HIV treatment as prevention (TasP), encompassing widespread HIV testing and immediate initiation of free antiretroviral treatment (ART), was piloted under the Seek and Treat for Optimal Prevention of HIV/AIDS initiative (STOP) in British Columbia, Canada. We compared the time from HIV diagnosis to treatment initiation, and from treatment initiation to first virologic suppression, before (2005-2009) and after (2010-2016) the implementation of STOP., Methods: In this population-based cohort study, we used longitudinal data of all people living with an HIV diagnosis in BC from 1996 to 2017. We included those aged 18 years or older who had never received ART and had received an HIV diagnosis in the 2005-2016 period. We defined the virologic suppression date as the first date of at least 2 consecutive test results within 4 months with a viral load of less than 200 copies/mL. Negative binomial regression models assessed the effect of STOP on the time to ART initiation and suppression, adjusting for confounders. All p values were 2-sided, and we set the significance level at 0.05., Results: Participants who received an HIV diagnosis before STOP ( n = 1601) were statistically different from those with a diagnosis after STOP ( n = 1700); 81% versus 84% were men ( p = 0.0187), 30% versus 15% had ever injected drugs ( p < 0.0001), and 27% versus 49% had 350 CD4 cells/μL or more at diagnosis ( p < 0.0001). The STOP initiative was associated with a 64% shorter time from diagnosis to treatment (adjusted mean ratio 0.36, 95% confidence interval [CI] 0.34-0.39) and a 21% shorter time from treatment to suppression (adjusted mean ratio 0.79, 95% CI 0.73-0.85)., Interpretation: In a population with universal health coverage, a TasP intervention was associated with shorter times from HIV diagnosis to treatment initiation, and from treatment initiation to viral suppression. Our results show accelerating progress toward the United Nations' 90-90-90 target of people with HIV who have a diagnosis, those who are on antiretroviral therapy and those who are virologically suppressed, and support the global expansion of TasP to accelerate the control of HIV/AIDS., Competing Interests: Competing interests: Julio Montaner has received institutional grants from Gilead Sciences and Merck. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery., Methods: We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework., Results: Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one's children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women's intrinsic motivation., Conclusion: The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men's role in couples' joint decision-making and women's maternal love as motivators for adherence., Competing Interests: The authors have declared that no competing interests exist.

The development of metabolic derangements as a result of HIV treatment has been an important area of research since the introduction of zidovudine in the 1980's. Antiretroviral therapy has intensely evolved in the last three decades, with new drugs gradually incorporated into everyday clinical practice. With the life expectancy of people living with HIV rapidly approaching that of their HIV-negative counterparts, the influence of these antiretrovirals on the development of the components of the metabolic syndrome remains of major interest to clinicians and their patients. In this review, we aimed to discuss the impact of cART on components of the metabolic syndrome, i.e., weight, plasma lipid levels, plasma glucose levels, and blood pressure, describing the influence of cART classes and of individual antiretrovirals. We also aimed to outline the limitations of the research conducted to date and the remaining knowledge gaps in this area.

HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16-0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population., (© 2021. The Author(s).)

Background: Early combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study compares HIV reservoirs in children (5-12 years) and adolescents (13-17 years) who started cART <6 months (early [E-] group) or >2 years (late [L-] group)., Methods: The ANRS-EP59-CLEAC study prospectively enrolled 76 patients perinatally infected with HIV-1 who reached HIV-RNA <400 copies/mL <24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T-cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cell (PBMC) stimulation., Results: Total HIV-DNA levels were lower in early- versus late-treated patients (children: 2.14 vs 2.87 log copies/million PBMCs; adolescents: 2.25 vs 2.74 log; P < .0001 for both). Low reservoir was independently associated with treatment precocity, protective HLA, and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than other patients (4 vs 54 months; P = .03). In those with sustained virological control, transitional and effector memory CD4+ T cells were less infected in the E-group than in the L-group (P = .03 and .02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between groups., Conclusions: Early cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation., Methods: ART-naïve people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells]., Results: Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04)., Conclusions: Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk., Competing Interests: K.M.E. has received research funding from Gilead Sciences (paid to the University of Colorado) and consulting fees from ViiV Pharmaceuticals and Theratechnologies (paid to the University of Colorado). The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown., Methods: Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viremia in cART-suppressed infants., Results: Baseline HIV DNA (median 2.8 log10 copies/million peripheral blood mononuclear cells, range 0.7-4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviremia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound., Conclusions: With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Pregnant women using antiretrovirals (ARVs) may have persistent vaginal viral shedding, which could be associated with sexual and perinatal HIV transmission. However, there are scant data on vaginal viral load (VVL) in pregnant women with undetectable plasma viral load (PVL)., Methods: This study was a post hoc analysis of an open-label randomized trial to evaluate the virologic response of 2 ART regimens. The participants were ART-naive women living with HIV initiating ART regimens between 20 and 36 weeks of pregnancy recruited at 19 clinical sites in 6 countries. Participants were randomized to receive 400 mg of raltegravir 2 times a day or 600 mg of efavirenz 4 times a day in addition to 150 mg of lamivudine and 300 mg of zidovudine 2 times a day. VVL and PVL tests were performed at every study visit. The primary outcome measures were HIV-1 PVL and VVL at maternal study week 4 and rates of perinatal HIV transmission., Results: A total of 408 were enrolled, of whom 323 had VVL samples 4 weeks after enrollment and were included in this analysis. Among women with undetectable/nonquantifiable PVL during ART, the overall rate of quantifiable VVL at week 4 was 2.54% (7/275). Of the 275 with nonquantifiable PVL, 99.1% (115/116) and 96.2% (153/159) had nonquantifiable VVL in the efavirenz and raltegravir arms, respectively. None of the 7 women with quantifiable VVL at the week 4 study visit transmitted HIV to their infants., Conclusions: Detectable VVL in pregnant women with undetectable/nonquantifiable PVL while receiving ART was rare and not associated with perinatal HIV transmission., Competing Interests: R.L.M. and D.E.S. report grants from US National Institute of Allergy and Infectious Diseases (NIAID) and nonfinancial support from US Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) through Westat, Inc., during the conduct of the study, and grants from NIAID and NICHD through the University of Michigan, outside the submitted work. L.M.F. reports grants from NICHD, NIAID, and IMPAACT during the conduct of the study and additional support from the Molecular Profiling and Computational Biology Core of the University of Washington and Fred Hutch Center for AIDS Research (P30 AI027757). M.M. reports grants from NICHD and National Institutes of Health (NIH), during the conduct of the study, and grants from Merck & Co, ViiV Healthcare, and Gilead Sciences, outside the submitted work. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH), under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACTLC), and by NICHD contract number HHSN275201800001I. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination (BIC/FTC/TAF 50/200/25 mg) is recommended as an initial regimen in patients who are antiretroviral (ARV)-naïve or virologically suppressed on a stable ARV regimen. However, no real-world pharmacokinetic (PK) data are available in treatment-experienced patients with antiretroviral resistance receiving BIC/FTC/TAF plus a boosted protease inhibitor., Setting/methods: This prospective, single-center, nonrandomized pharmacokinetic study enrolled adult treatment-experienced persons with HIV and creatinine clearance >30 mL/min receiving BIC/FTC/TAF + DRV/c as part of routine clinical care. Steady-state PK profiles of BIC, TAF, tenofovir (TFV), and DRV after daily dosing of BIC/FTC/TAF + darunavir/cobicistat (DRV/c) were obtained with samples at predose and 0.5, 1, 2, and 4 hours postdose. The AUC0-24 at steady state was extrapolated by imputing C0 for C24 for each participant (AUC0-tau,exp)., Results: Nine participants were enrolled with a median age of 59 years (range 54-67) and median number of years on ART of 19 (range 5.8-30). The median (interquartile range [IQR]) BIC AUC0-tau,exp and Cmax values were 128.9 µg*h/mL (78.1-159.5) and 6.9 µg/mL (5.1-9.8), respectively. The median (IQR) TAF AUC0-tau,exp and Cmax values were 0.376 µg*h/mL (0.199-0.430) and 0.276 µg/mL (0.149-0.543), respectively. Predose concentrations of TFV and DRV were comparable with historical data., Conclusion: Treatment-experienced persons with HIV receiving BIC/FTC/TAF + darunavir/cobicistat (DRV/c) had BIC exposures (AUC0-tau) that were increased by approximately 26% compared with historical PK data. Although TAF exposures were substantially increased, plasma TFV was only modestly higher. These results suggest that BIC/TAF/FTC + DRV/c is a viable antiviral regimen option for treatment-experienced persons., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: In clinical practice, not all human immune deficiency virus (HIV) positive individuals who received highly active antiretroviral therapy (HAART) achieve the desired concordant response characterized by a sustained viral suppression or immune recovery. The expected success of HAART doesn't occur in all treated patients and a discordant response between CD4 count and the viral load (VL) has been a major concern in the treatment of HIV patients. Thus, this study is designed to describe the factors associated with immunological and virological discordant responses to HAART among adult HIV positive individuals.A hospital-based cross-sectional study with secondary data review was conducted on 423 HIV positive individuals on HAART from February 1 to April 30, 2017. Socio-demographic characteristics, clinical data and about 10 mL of blood specimen for HIV VL, and CD4 count measurement were collected. The data was entered into SPSS version 20 and descriptive, bivariate, and multivariate logistic regression analysis was employed.The mean age of the patients at study time was 39 (±9.8). The average follow-up duration of patients on antiretroviral therapy (ART) was 7 (±3) years. The prevalence of immunological discordance and virological discordance to HAART were 13.2% and 47%, respectively. With multivariate logistic regression analysis duration of follow-up on ART ≤ 6 years (adjusted odds ratio [AOR] = 3.29 (1.80-6.03), P ≤ .001) and VL ≥20 copies/mm3 (AOR = 3.08 [1.70-5.61], P ≤ .001) were significant factors for immunological discordance conversely the patients who switched drug as a result of TB (AOR = 3.33 [1.10-10.08], P = .03) was significant factors for virological discordance.The prevalence of immunological discordance and virological discordance to HAART among HIV patients is high. Patients with the duration of follow-up on ART ≤ 6 years, VL ≥ 20 copies/mm3 and patients who switched drugs as a result of TB were significant factors for discordance. Hence, intensive adherence support and counseling should be provided to achieve the UNAIDS 90 target. HIV positive individuals co-infected with TB, who have had VL ≥ 20 copies/mm3 and who are ≤6 years duration of follow-up on ART need to be carefully monitored. In addition, national based study of discordant groups is recommended., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Comparisons between rilpivirine (RPV) and integrase strand transfer inhibitors (INSTIs) in antiretroviral therapy (ART)-naïve HIV-infected individuals are currently lacking. This study aimed to compare, in an observational cohort setting, the durability of treatment with RPV-based and INSTI-based first-line regimens., Methods: Patients who started first-line ARTs based on RPV or INSTIs, with HIV-RNA < 100 000 copies/mL and CD4 cell count > 200 cells/μL were included. The primary endpoint was the cumulative probability of treatment failure (TF = virological failure [confirmed HIV-RNA > 50 copies/mL] or discontinuation of the anchor drug in the regimen), as assessed by the Kaplan-Meier method. A multivariable Cox regression was used to control for potential confounding., Results: Of the 1991 included patients, 986 started ART with an RPV-based regimen and 1005 with an INSTIs-based regimen. The median (IQR) follow-up was 20 (10, 35) months. The cumulative 2-year probability of TF with RPV (9.1% [95% 7.2, 11.1]) was lower than that observed in the INSTIs group (16.6% [13.8, 19.4], P = 0.0002) but not when compared with dolutegravir (DTG) alone. Starting ART with an INSTIs-based regimen vs. RPV was associated with a higher risk of TF after controlling for potential confounding factors (adjusted hazard ratio, AHR [95% CI]: 1.64 [1.28, 2.10]; P < 0.001). The results were similar when restricting the analysis to single-tablet regimens, although the probability of virological success was higher for INSTIs and DTG., Conclusions: In ART-naïve patients with low viral loads and high CD4 counts, the risk of treatment failure was lower in those who started RPV-based vs. INSTIs-based regimens other than DTG-based ones., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/purpose: Growth arrest-specific 6 (Gas6) protein is involved in cell proliferation, differentiation, adhesion, migration in response to inflammatory processes. Human immunodeficiency virus (HIV) infection induces a chronic inflammatory condition and combination of antiretroviral therapy improves immune function and decreases the inflammatory state. The aim of this study was to assess the implications of Gas6 in chronic inflammation status of HIV-infected patients undergoing different third regimens of antiretroviral therapy. The Gas6 may be a marker of chronic inflammation of HIV-infected patients., Methods: A total of 356 adult males, including 258 HIV-infected patients and 98 healthy controls, were recruited. The demographic and clinical characteristics of the patients were collected. Laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), hepatitis B and C viruses, and serum biochemistry. Plasma Gas6 concentrations were determined., Results: The values of Gas6 were lower in HIV patients compared to healthy subjects (14.3 ± 6.4 vs 21.5 ± 15.2, p = 0.01). HIV patients that received antiviral regimen with abacavir had similar Gas6 level than those who received antiviral regimens with tenofovir (14.3 ± 6.5 vs 13.8 ± 5.9, p = 0.99). HIV patients that received antiviral regimen with protease inhibitors (PIs) had lower Gas6 level (13.1 ± 3.5 vs 14.2 ± 6.6 vs 14.6 ± 6.5, p = 0.03) than those who received antiviral regimens with non-nucleoside reverse transcriptase inhibitors (nNRTIs) and integrase inhibitors (INSTIs), respectively., Conclusions: Decreased plasma Gas6 concentrations were observed in HIV patients. Gas6 levels are associated with different third regimen of highly active antiretroviral therapy. Gas6 may represent a unique marker for assessing the chronic inflammation state difference among cART regimens in HIV patients., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021. Published by Elsevier B.V.)