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Background: In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests., Methods: For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment., Findings: Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27-44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95-100]) but the specificity was higher for TB-MBLA (90% [83-96]) than for Xpert-Ultra (78% [68-86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75% [65-83]) but higher specificity (98% [93-100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80-100) and was 100% (95% CI 86-100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but the rate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8 weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8 weeks to those who were smear microscopy negative., Interpretation: TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy., Funding: European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health., Competing Interests: Declaration of interests WSa and SHG provide pro bono advice for LifeArc, a company that is developing TB-MBLA for clinical use. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We present findings from a large cohort of individuals treated during primary HIV infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies., Methods: Individuals who fulfilled the criteria of PHI and started ART within 3 months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009 and 2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015-2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression., Results: Two hundred four individuals enrolled, 144 from 2009 to 2015 and 90 from 2015 to 2020; median follow-up was 33 months. At PHI, the median age was 33 years; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009-2015, compared with 29% in 2015-2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4 + cell count more than 900 cells/μl [hazard ratio 0.99 (95% confidence interval, 95% CI 0.98-0.99), P  = 0.02) and CD4/CD8 more than 1.0 (hazard ratio 0.98 (95% CI 0.97-0.99)., Conclusion: Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study., Methods: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m 2 and had been on stable ART for at least 90 consecutive days with an HIV-1 viral load of less than 50 copies per mL at a participating IMPAACT study site. Participants had to be willing to continue their pre-study ART during cohort 1. The primary objectives of the study were to confirm doses for oral and injectable cabotegravir and for injectable rilpivirine in adolescents living with HIV. This analysis of participant-reported outcomes included a face scale assessment of pain at each injection and a Pediatric Quality of Life Inventory (PedsQL) at baseline and week 16 for participants in the USA, South Africa, Botswana, and Thailand. A subset of 11 adolescents and 11 parents or caregivers in the USA underwent in-depth interviews after receipt of one or two injections. This trial is registered at ClinicalTrials.gov, NCT03497676., Findings: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections., Interpretation: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV., Funding: National Institutes of Health and ViiV Healthcare., Competing Interests: Declaration of interests KC, SB, and DEY received grant funding from the National Institutes of Health (NIH) to support work on this protocol. JC received support to travel and attend a meeting from the IMPAACT Network. AHG's institution has Clinical Trial agreements with ViiV to support work on this study and has a Clinical Trial agreement with Janssen to support other studies; and AHG received payment from ViiV Healthcare to attend a Pediatric Advisory Board meeting. KB, RM, and SW had funds paid to their institution by ViiV Healthcare related to their work on this manuscript. HC and RMVS-R are employees of Janssen and have stock and stock options with Johnson & Johnson. ALA is site principal investigator for multi-site Gilead and Merck studies, a Gilead expert advisory board attendee, a Merck consultant, expert advisory board attendee for ViiV, presenter at a workshop supported by ViiV, part of the Speaker's Bureau for the Simply Speaking HIV Prevention Series, an expert witness, an unpaid Advocates for Youth Board Chair, an unpaid member of the Well Project Board, and an unpaid HIVMA Vice Chair. AC-G is a ViiV Healthcare consultant and has received funds from Merck and Janssen. CCM, VC, and CH are employees at ViiV Healthcare. CCM and VC own GSK stock or stock options. DEY was previously an unpaid technical advisor for the following non-profit institutions: Cover the Globe and Maipelo Trust. JH is an employee at GSK. DEY is an employee of NIH. AA, AB, EDL, RO, CB-M, CS-A, BH, JK, and JDA declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years)., Methods: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis., Results: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years., Conclusions: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities., Trial Registration Number: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019)., (© 2024. The Author(s).)

Objectives: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as preexposure prophylaxis (PrEP), using ex-vivo rectal tissue infections and drug concentration measures in blood and rectal tissue., Design/methods: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex-vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, 2 h after two pills or 7 days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection., Results: Twelve and 11 men were analyzed in the 2 h-double dose and 7 days-single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144 pg/ml/mg (IQR[-259;-108]) for the 2 h-double dose group ( P  = 0.0005) and -179 pg/ml/mg (IQR [-253;-86]) for the 7 days-single dose group ( P  = 0.001), with no differences between groups ( P  = 0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at 7 days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose ( R  = -0.84; P  = 0.0001)., Conclusion: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 h after a double dose or 7 days of a daily dose. At 2 h, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates., Methods: We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk., Results: There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk., Conclusions: The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs., Competing Interests: Potential conflicts of interest. The 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) 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.)

Background: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens., Methods: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38., Findings: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups., Interpretation: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine., Funding: ViiV Healthcare., Competing Interests: Declaration of interests GM has received fees for educational activities or advisory services from Gilead, Merck Sharp & Dohme, Theratechnologies, and ViiV Healthcare. AC has received fees for educational activities and consultancies, and financial support for attending conferences from Gilead, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. SR has received honoraria for presentations and scientific advice from Merck Sharp & Dohme, Theratechnologies, GSK, Janssen Cilag, ViiV Healthcare, and Gilead, and research grants paid to his institution from Janssen Cilag, ViiV Healthcare, and Gilead. MM has participated in lectures and advisory boards for ViiV Healthcare, Janssen, and MSD. BJ is a ViiV Healthcare employee and holds GSK stock. RG is an employee of GSK and owns shares in the company. AP has delivered lectures and participated in advisory boards for ViiV Healthcare, Janssen, Gilead, and MSD. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.

Objectives: Cabotegravir + rilpivirine (CAB + RPV) dosed monthly or every 2 months is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virological suppression. This post hoc analysis summarizes outcomes for Asian participants through week 96., Methods: Data from Asian participants naive to CAB + RPV randomized to receive dosing every 4 weeks (Q4W) or every 8 weeks (Q8W) in the FLAIR (NCT02938520) and ATLAS-2M (NCT03299049) phase 3/3b studies were pooled. The proportion of participants with plasma HIV-1 RNA ≥50 and <50 copies/mL (per FDA Snapshot algorithm), incidence of confirmed virological failure (CVF; two consecutive HIV-1 RNA ≥200 copies/mL), pharmacokinetics, safety, and tolerability through week 96 were assessed., Results: Overall, 41 Asian participants received CAB + RPV (Q8W, n = 17; Q4W, n = 24). At week 96, 83% (n = 34/41) of participants maintained HIV-1 RNA <50 copies/mL, none had HIV-1 RNA ≥50 copies/mL, and 17% (n = 7/41) had no virological data. No Asian participant met the CVF criterion. Drug-related adverse events occurred in 44% (n = 18/41) of participants; none were Grade ≥3. All injection site reactions were Grade 1 or 2; median duration was 2 days and most resolved within 7 days (90%, n = 390/435). CAB and RPV trough concentrations remained well above their respective protein-adjusted 90% inhibitory concentrations (CAB, 0.166 μg/mL; RPV, 12 ng/mL) through week 96., Conclusions: CAB + RPV LA demonstrated high efficacy, with no participants having CVF, and an acceptable safety profile in Asian participants through week 96. These data support CAB + RPV LA as a complete regimen for the maintenance of HIV-1 virological suppression in Asian individuals., (© 2023 ViiV Healthcare. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objectives: Due to the paucity of literature on risk factors for tuberculosis (TB)-related death, we determine the sociodemographic and clinical risk factors associated with TB-related deaths among adult pulmonary TB (PTB) patients on treatment in Selangor, Malaysia., Design: Retrospective cohort study., Setting: Routinely collected primary care data from all government TB clinics in Selangor., Participants: Data of 24 570 eligible adult PTB patients from 2013 to 2019 were obtained from Selangor's State Health Department surveillance records. We included PTB patients aged at least 15 years old at the time of diagnosis with complete documentation of the dates of diagnosis, treatment initiation, end of treatment/follow-up and treatment outcomes. We excluded patients whose diagnoses were changed to non-TB, post-mortem TB diagnosis and multidrug-resistant TB (MDR-TB) patients., Primary and Secondary Outcome Measures: TB-related death, determined from the recorded physicians' consensus during the TB mortality meeting., Results: TB-related death was significantly associated with far (adjusted HR (aHR) 9.98, 95% CI 4.28 to 23.28) and moderately advanced (aHR 3.23, 95% CI 1.43 to 7.31) radiological findings at diagnosis; concurrent TB meningitis (aHR 7.67, 95% CI 4.53 to 12.98) and miliary TB (aHR 6.32, 95% CI 4.10 to 9.74) involvement; HIV positive at diagnosis (aHR 2.81, 95% CI 2.21 to 3.57); Hulu Selangor (aHR 1.95, 95% CI 1.29 to 2.93), Klang (aHR 1.53, 95% CI 1.18 to 1.98) and Hulu Langat (aHR 1.31, 95% CI 1.03 to 1.68) residing districts; no formal education (aHR 1.70, 95% CI 1.23 to 2.35); unemployment (aHR 1.54, 95% CI 1.29 to 1.84), positive sputum smear acid-fast bacilli (AFB) at diagnosis (aHR 1.51, 95% CI 1.22 to 1.85); rural residency (aHR 1.39, 95% CI 1.13 to 1.72) and advancing age (aHR 1.03, 95% CI 1.02 to 1.03)., Conclusions: Far and moderately advanced radiological findings, concurrent TB meningitis and miliary TB involvement, HIV positive, Hulu Selangor, Klang and Hulu Langat residing districts, no formal education, unemployment, positive sputum smear AFB, rural residency and advancing age are risk factors of TB-related death. Our findings should assist in identifying high-risk patients requiring interventions against TB-related death., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In two phase 3 trials for first-line therapy in adults with HIV-1, doravirine showed non-inferior efficacy, a favourable safety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks. Here we report 192-week results from both studies., Methods: DRIVE-FORWARD and DRIVE-AHEAD are multicentre, double-blind, randomised, active comparator-controlled, phase 3 trials of first-line antiretroviral treatment in adults with HIV-1. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy, had plasma HIV-1 RNA 1000 copies per mL or more at screening, had no known resistance to any of the trial drugs, and had creatinine clearance 50 mL per min or more. DRIVE-FORWARD was conducted at 125 sites in 15 countries and compared doravirine (100 mg) with ritonavir-boosted darunavir (ritonavir [100 mg] and darunavir [800 mg]), each administered orally once daily with two nucleoside or nucleotide reverse transcriptase inhibitors (tenofovir disoproxil fumarate [300 mg] and emtricitabine [200 mg] or abacavir sulfate [600 mg] and lamivudine [300 mg]). DRIVE-AHEAD was conducted at 126 sites in 23 countries and compared doravirine (100 mg), lamivudine (300 mg), and tenofovir disoproxil fumarate (300 mg) with that of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), all administered orally once daily. DRIVE-FORWARD enrolment was between Dec 1, 2014, and June 1, 2020, and DRIVE-AHEAD enrolment was between June 10, 2015, and Aug 10, 2020. After the 96-week double-blind phase, eligible participants could enter an open-label extension and either continue doravirine or switch from comparator to doravirine for an additional 96 weeks. Efficacy (HIV-1 RNA <50 copies per mL) and safety assessments (adverse events and changes in laboratory parameters) were pooled. The DRIVE-FORWARD and DRIVE-AHEAD trials were registered with ClinicalTrials.gov, NCT02275780 and NCT02403674., Findings: Of 1494 participants treated in the double-blind phase (1261 [84%] male and 233 [16%] female), 550 continued doravirine and 502 switched to doravirine in the extension. Using the FDA snapshot approach, HIV-1 RNA less than 50 copies per mL was maintained in 457 (83%) of 550 participants who continued doravirine and 404 (80%) of 502 participants who switched to doravirine. Protocol-defined virological failure and development of resistance were low, occurring mainly before week 96. Two (<1%) of 550 participants who continued doravirine reported serious drug-related adverse events, and three (1%) who continued doravirine and one (<1%) of 502 who switched to doravirine discontinued due to drug-related adverse events. Participants continuing or switching to doravirine showed generally favourable lipid profiles, little weight gain, and small decreases in estimated glomerular filtration rates, with no discontinuations due to increased creatinine or renal adverse events., Interpretation: Favourable efficacy and safety profiles for doravirine at week 96 were maintained through to week 192 in participants who continued or switched to doravirine, supporting use of doravirine for long-term first-line HIV-1 treatment and for virologically suppressed adults switching therapy., Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA., Competing Interests: Declaration of interests SK, HC, HW, VT, ZJX, EA-A, PS, HT, and RL are current or former employees of Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA, and may own stock or options in Merck & Co, Rahway, NJ, USA. CO has received grant funding from Gilead Sciences, Merck & Co, ViiV Healthcare, Janssen Pharmaceuticals, and AstraZeneca, and has served on advisory boards for Gilead Sciences, Merck & Co, ViiV Healthcare, and Janssen Pharmaceuticals. J-MM has received grant funding from Gilead Sciences, and has served on advisory boards for Aelix, Gilead Sciences, Merck & Co, and ViiV Healthcare. PC has received grant funding from ViiV Healthcare and Merck & Co; has received consulting fees from ViiV Healthcare; has received payment or honoraria from ViiV Healthcare, Gilead Sciences, and Janssen Pharmaceuticals; and has served on an advisory board for Moderna. KS and JL declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Selection of an antiretroviral regimen for people living with HIV (PLWH) involves various clinical considerations, such as comorbidities, archived drug resistance mutations, concomitant medications, and potential drug interactions and side effects. Alterations in the surface area and pH of the gastrointestinal tract following bariatric surgery may alter absorption, antiretroviral pharmacokinetics and viral suppression. Data on the efficacy of antiretroviral (ARV) therapy in PLWH who have undergone bariatric surgery are limited or lacking for new antiretrovirals, such as dolutegravir and bictegravir., Methods: This case series reports virologic outcomes and side effects in eight cases of PLWH receiving ARV therapy who underwent bariatric surgery. A systematic literature review was performed to review the available literature on the efficacy and safety of antiretroviral regimens in PLWH who have undergone bariatric surgery., Results: Virologic suppression was not impacted for obese PLWH who underwent bariatric surgery following failure of life-style modifications and pharmacological therapy., Conclusions: There were no deleterious effects on HIV progression for PLWH that underwent bariatric surgery. More prospective research is required to validate the effects of bariatric surgery on immunologic and virologic function outcomes. Close involvement of HIV and surgical specialists is recommended to manage ARV therapy in patients undergoing bariatric surgery., 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.

Clinical trials of dual regimen dolutegravir/lamivudine (DOL/3TC) demonstrated potent efficacy and favorable safety in both antiretroviral therapy-naïve and -experienced patients, but data on older people are lacking. We aimed to evaluate virological efficacy and safety of DOL/3TC in suppressed older patients over a 12-month period. We performed a retrospective cohort study evaluating people living with HIV (PLWHIV) aged ≥65 years at our HIV Clinic who were switched to DOL/3TC. Eligible patients had baseline HIV-1 RNA <20 copies/mL, and no previous virological failures or known resistance mutations for lamivudine or dolutegravir. Inclusion criteria were met by 72 patients: 59 were men, median age was 69.2 years, and one or more comorbidities were present in 89% of patients. The most common reason for switch was simplification, followed by drug-drug interactions (DDIs) and toxicities. After 12 months, 64 (88.9%, by the intention-to-treat analysis) patients maintained HIV-1 RNA <20 copies/mL, and reasons for treatment failure were virological failure in three cases, adverse events in three, and missing data in two. Genotype resistance testing showed no resistance mutations for lamivudine or dolutegravir in subjects with virological failure. The number of potential DDIs decreased from 92 to 12 after switching to DOL/3TC, and a significant reduction in median total and low-density lipoprotein cholesterol was reported, while median change in body weight was not significant. In this real-life cohort, switching to DOL/3TC was associated with maintenance of virological control and good tolerability among persons aged >65 years, supporting use of this dual regimen in older PLWHIV.

An effective HIV-1 vaccine is a global health priority but has remained elusive for more than 40 years. Key scientific hurdles that have hampered vaccine development are the unprecedented genetic variability of the virus, the rapid establishment of persistent viral latency, and the challenges associated with induction of broadly neutralising antibodies. Clinical trials have been instrumental in evaluating scientific concepts and testing vaccine strategies. This Review discusses lessons learned from clinical trials of HIV-1 vaccines, current technologies that are being explored, and future considerations in the development of a safe and effective HIV-1 vaccine., Competing Interests: Declaration of interests DHB is a co-inventor on HIV-1 vaccine patents that have been licensed. JPN declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya., Methods: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters., Results: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016-20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011-15), but dropped to 6.5% (2016-20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000-08], indicating propagation over 12 years., Conclusions: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: The main objective of this analysis was to evaluate the impact of pre-existing drug resistance by next-generation sequencing (NGS) on the risk of treatment failure (TF) of first-line regimens in participants enrolled in the START study., Methods: Stored plasma from participants with entry HIV RNA >1000 copies/mL were analysed using NGS (llumina MiSeq). Pre-existing drug resistance was defined using the mutations considered by the Stanford HIV Drug Resistance Database (HIVDB v8.6) to calculate the genotypic susceptibility score (GSS, estimating the number of active drugs) for the first-line regimen at the detection threshold windows of >20%, >5%, and >2% of the viral population. Survival analysis was conducted to evaluate the association between the GSS and risk of TF (viral load >200 copies/mL plus treatment change)., Results: Baseline NGS data were available for 1380 antiretroviral therapy (ART)-naïve participants enrolled over 2009-2013. First-line ART included a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 976 (71%), a boosted protease inhibitor in 297 (22%), or an integrase strand transfer inhibitor in 107 (8%). The proportions of participants with GSS <3 were 7% for >20%, 10% for >5%, and 17% for the >2% thresholds, respectively. The adjusted hazard ratio of TF associated with a GSS of 0-2.75 versus 3 in the subset of participants with mutations detected at the >2% threshold was 1.66 (95% confidence interval 1.01-2.74; p = 0.05) and 2.32 (95% confidence interval 1.32-4.09; p = 0.003) after restricting the analysis to participants who started an NNRTI-based regimen., Conclusions: Up to 17% of participants initiated ART with a GSS <3 on the basis of NGS data. Minority variants were predictive of TF, especially for participants starting NNRTI-based regimens., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Human Immunodeficiency Virus (HIV)-positive individuals lost to follow-up from particular clinics may not be lost to care (LTC). After linking Vanderbilt's Comprehensive Care Clinic cohort to Tennessee's statewide HIV surveillance database, LTC decreased from 48.4% to 35.0% at 10 years. Routine surveillance linkage by domestic HIV clinics would improve LTC and retention measure accuracy., Competing Interests: Potential conflicts of interest. P. F. R. received honoraria from Gilead & Janssen Pharmaceuticals in 2021. 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) 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.)

Objectives: The COVID-19 pandemic's impact on initiation and effectiveness of antiretroviral therapy (ART) in people diagnosed with HIV remains unclear. We evaluated critical delays in HIV care in people diagnosed before and during the pandemic in ex-Aquitaine, France., Methods: We considered adults diagnosed with HIV-1 in 2018-2021 and enrolled in the ANRS CO3 AQUIVIH-NA and followed them until October 10, 2022 for those diagnosed during the pandemic (April 01, 2020-December 31, 2021) and until March 31, 2020 for historical controls. We compared their characteristics at inclusion and the median time between diagnosis and ART initiation, ART initiation and viral suppression, and diagnosis and virologic, suppression (effective management)., Results: Eighty-three individuals were diagnosed during the pandemic versus 188 during the prepandemic period. Median follow-up was 549 (interquartile range: 329-713) days. Populations were similar in sex, age, HIV acquisition mode, hospital type, and clinical characteristics at diagnosis; however, fewer were foreign-born during the pandemic (15.7% versus 33.5%, P = 0.003). The probability of ART initiation, therapeutic success, and effective management was higher in people living with HIV (PLWH) diagnosed during the pandemic in adjusted analyses (hazard ratio [HR]: 2.0; 95% CI: 1.5 to 2.7; HR: 1.7; 95% CI: 1.2 to 2.3; HR: 1.8; 95% CI: 1.3 to 2.6, respectively). Those diagnosed during the pandemic were 2.3 (95% CI: 1.2 to 4.1) times more likely to be virologically suppressed within six months of diagnosis compared with historical controls., Conclusions: Pandemic-related reorganizations may have resulted in newly diagnosed PLWH being prioritized; however, the lower proportion of foreign-born PLWH diagnosed during the pandemic period, likely because of reduced migration and potential delays in diagnosis, may contribute to these preliminary findings., Competing Interests: The authors declare no conflicts of interest in relation to this manuscript. S.F. has received financial support from Gilead Sciences, MSD and ViiV Healthcare to attend scientific conferences. D.B. has received speaking fees from Gilead Healthcare, MSD, ViiV Healthcare and outside the submitted work., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Infants born with HIV-1 require lifelong antiretroviral therapy (ART). We aimed to assess whether very early ART in neonates might restrict HIV-1 reservoirs, an important step towards ART-free remission., Methods: IMPAACT P1115 is an ongoing, phase 1/2, proof-of-concept study in which infants were enrolled at 30 research clinics in 11 countries (Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the USA, Zambia, and Zimbabwe) into two cohorts. Infants at least 34 weeks' gestational age at high risk for in-utero HIV-1 with either untreated maternal HIV-1 (cohort 1) or who were receiving pre-emptive triple antiretroviral prophylaxis outside of the study (maternal ART permissible; cohort 2) were included. All infants initiated treatment within 48 h of life. Cohort 1 initiated three-drug nevirapine-based ART, and cohort 2 initiated three-drug nevirapine-based prophylaxis then three-drug nevirapine-based ART following HIV diagnosis by age 10 days. We added twice-daily coformulated oral ritonavir 75 mg/m 2 and lopinavir 300 mg/m 2 from 14 days of life and 42 weeks postmenstrual age. We discontinued nevirapine 12 weeks after two consecutive plasma HIV-1 RNA levels below limit of detection. We tracked virological suppression, safety outcomes, and meeting a predetermined biomarker profile at age 2 years (undetectable RNA since week 48, HIV-1 antibody-negative, HIV-1 DNA not detected, and normal CD4 count and CD4 percentage) to assess qualification for analytical treatment interruption. This study is registered with ClinicalTrials.gov, NCT02140255., Findings: Between Jan 23, 2015, and Dec 14, 2017, 440 infants were included in cohort 1 and 20 were included in cohort 2. 54 of these infants (34 from cohort 1 and 20 from cohort 2) had confirmed in-utero HIV-1 and were enrolled to receive study ART. 33 (61%) of 54 infants were female and 21 (39%) were male. The estimated probability of maintaining undetectable plasma RNA through to 2 years was 33% (95% CI 17-49) in cohort 1 and 57% (28-78) in cohort 2. Among infants maintaining protocol-defined virological control criteria through to study week 108, seven of 11 (64%, 95% CI 31-89) in cohort 1 and five of seven (71%, 29-96) in cohort 2 had no detected HIV-1 DNA. Ten of 12 (83%, 52-100) in cohort 1 and all seven (100%, 59-100) in cohort 2 tested HIV-1 antibody-negative at week 108. Among 54 infants initiated on very early ART, ten (19%; six in cohort 1 and four in cohort 2) met all criteria for possible analytical treatment interruption. Reversible grade 3 or 4 adverse events occurred in 15 (44%) of 34 infants in cohort 1 and seven (35%) of 20 infants in cohort 2., Interpretation: Very early ART for in-utero HIV-1 can achieve sustained virological suppression in association with biomarkers indicating restricted HIV-1 reservoirs by age 2 years, which might enable potential ART-free remission., Funding: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health., Competing Interests: Declaration of interests MM receives research support from Gilead Sciences, ViiV Healthcare, and Merck. EVC serves as a consultant to Melinta Pharmaceuticals. EGC's spouse holds an equity interest in AbbVie. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy., Design: An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1., Methods: Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC, and TAF. Neonates ( n  = 29) were followed from birth to 4-8 weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50 copies/ml at delivery (missing = excluded) was evaluated., Results: Mean areas under the concentration-time curve over the dosing interval (AUC tau ) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUC tau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUC tau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 h. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission., Conclusion: Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Previous studies have indicated different immunological recovery trajectories based on CD4 count or CD4/CD8 ratio. However, these immune indicators are interconnected, and relying solely on one indicator may lead to inaccurate estimates. Therefore, it is essential to develop a comprehensive trajectory model that integrates CD4 count, CD8 count and CD4/CD8 ratio., Methods: We utilized a group-based multi-trajectory model to characterize the latent cluster of recovery based on measurements of CD4 count, CD8 count and CD4/CD8 ratio over a period of up to 96 months following ART initiation. Subsequently, we investigated the characteristics associated with trajectory groups, especially sex and age. Cox model and Kaplan-Meier survival curve were employed to assess differences in all-cause, AIDS-related and non-AIDS related mortality between trajectory groups., Results: A total of 14,718 eligible individuals were followed for a median of 55 months. Longitudinal model identified four subgroups: group 1 (32.5%, low CD4 and CD4/CD8 inversion), group 2 (25.9%, high CD8 and CD4/CD8 inversion), group 3 (27.2%, slow recovery of CD4 and CD4/CD8 inversion) and group 4 (14.4%, rapid increase of CD4 and normal CD4/CD8). Immune recovery was slower in male than in female, and in elders than in youngers. Compared to group 2, group 1 (adjusted hazard ratio [aHR]=3.28; 95% CI 2.33-4.60) and group 3 (aHR=1.56; 95% CI 1.09-2.24) had increased risk of all-cause mortality after adjusting for other factors. Besides, group 1 (aHR=2.17) and group 3 (aHR=1.58) had higher risk of non-AIDS related mortality, and group 1 (aHR=5.92) had significantly increased risk of AIDS related mortality., Conclusion: Longitudinal trajectory analysis of multiple immune indicators can be employed to guide targeted interventions among vulnerable populations in clinical practice., 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 © 2023 Ma, Wang, Zhu, Li, Wang, Hao, Gao, Ma and Zhang.)

Pharmacy refill records (PRR), are an accessible strategy for estimating adherence in low- and middle-income countries (LMICs). However, the low-cost urine-tenofovir point-of-care test opens up the possibility of an objective metric of adherence that is scalable to LMICs. This study compared adherence to tenofovir-based regimens using urine-tenofovir point-of-care (POC) test with pharmacy refill records in a Nigerian population of HIV-positive persons. This was a cross-sectional study among 94 HIV-positive adults, which was conducted from June to August 2021, in a large outpatient clinic in Lagos, Nigeria. Adherence to pharmacy appointments was automatically calculated using a computerized pharmacy appointment system (FileMaker Pro™). Urine drops on the urine-tenofovir POC test strip developed 2 lines for a negative test (tenofovir absent) and one line for a positive test. Fisher's exact test was used to examine the association between pharmacy refill record and urine-tenofovir point-of-care test. Logistic regression was performed to predict viral suppression (<1000 copies/mL, based on WHO recommendations) using both methods of adherence determination. A Receiver Operating Characteristic (ROC) curve of the association between specificity and sensitivity was generated to evaluate the predictive value of adherence determined using pharmacy-refill record and urine-tenofovir point-of-care test in forecasting viral suppression. The statistical significance level was set at 0.05. Fisher's exact test showed no statistically significant difference in adherence using urine-tenofovir point-of-care test or pharmacy refill record. The logistic regression model showed that an increase in pharmacy-refill record of ≥ 95% was associated with viral suppression (P = .019). From the ROC curve, the sensitivity was same at 95.5% for both methods, but the specificity of the urine-tenofovir point-of-care test was greater (96.6% vs 95.5%) than pharmacy refill record (P = .837). Urine-tenofovir point-of-care test provided equivalent adherence data to pharmacy refill data., Competing Interests: This work was part of E.C.H’s PhD thesis at the University of Lagos, Nigeria. We have no other conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ([Formula: see text] standard deviation) was 44.0 ([Formula: see text] 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9-10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34-96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area., (© 2023. The Author(s).)

Objectives: To assess the impact of pretreatment low-abundance HIV drug-resistant variants (LA-DRVs) on virological outcomes among ART-naive HIV-1-infected Chinese people who initiated ART., Methods: A nested case-control study was conducted among HIV-1-infected individuals who had pretreatment drug resistance (PDR) genotypic results. Cases were defined as individuals with virological failure (HIV-1 RNA viral load ≥1000 copies/mL) after 1 year of ART, and controls were individuals from the same cohort whose viral load was less than 1000 copies/mL. Next-generation sequencing was used to identify low-abundance PDR mutations at detection thresholds of 10%, 2% and 1%. The mutant load was calculated by multiplying the abundance of HIV-1 drug-resistant variants by the pretreatment viral load. The impact of pretreatment low-abundance mutations on virological failure was estimated in logistic regression models., Results: Participants (43 cases and 100 controls) were included in this study for the analysis. The proportion of participants with PDR was higher in cases than in controls at different detection thresholds (44.2% versus 22.0%, P = 0.007 at 10% threshold; 58.1% versus 31.0%, P = 0.002 at 2% threshold; 90.7% versus 69.0%, P = 0.006 at 1% threshold). Compared with participants without PDR, participants with ≥10% detectable PDR mutations were associated with an increased risk of virological failure (adjusted OR 8.0, 95% CI 2.4-26.3, P = 0.001). Besides this, individuals with pretreatment LA-DRVs (2%-9% abundance range) had 5-fold higher odds of virological failure (adjusted OR 5.0, 95% CI 1.3-19.6, P = 0.021). Furthermore, LA-DRVs at 2%-9% abundance resistant to NRTIs and mutants with abundance of ≥10% resistant to NNRTIs had a 4-fold and 8-fold risk of experiencing virological failure, respectively. It was also found that a mutant load of more than 1000 copies/mL was predictive of virological failure (adjusted OR 7.2, 95% CI 2.5-21.1, P = 0.0003)., Conclusions: Low-abundance PDR mutations ranging from 2% to 9% of abundance can increase the risk of virological failure. Further studies are warranted to define a clinically relevant threshold of LA-DRVs and the role of NRTI LA-DRVs., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Our objectives were to investigate the characteristics of people living with HIV who presented with new or recurrent symptoms in the context of re-emergence of cerebrospinal fluid HIV RNA escape after antiretroviral therapy (ART) modification (termed relapse of CSF HIV RNA escape)., Methods: People living with HIV-1 with known CSF HIV RNA escape were identified, with clinical and laboratory data obtained from records in a tertiary centre. CSF HIV RNA escape was defined as quantifiable CSF HIV RNA in the presence of unquantifiable plasma HIV-RNA or CSF HIV RNA greater than plasma HIV RNA in cases where plasma HIV-RNA was quantifiable. Relapse was defined as a re-emergence of CSF HIV RNA escape with new symptoms after ART therapy intensification post-initial CSF HIV RNA escape., Results: Among 40 people living with HIV who presented with neurosymptomatic CSF HIV RNA, eight (20%) presented with a relapse of CSF HIV RNA escape. Symptoms on relapse included confusion (n = 2), cognitive decline (n = 2), cerebellar dysfunction (n = 2) and worsening of pre-existing seizures (n = 1). Prior to their relapse, three people underwent drug therapy modification, with two people stopping raltegravir intensification, and one person switched from tenofovir alafenamide, emtricitabine and raltegravir for a new regimen., Conclusions: People with a relapse of CSF HIV RNA escape within this cohort presented with varied symptoms similar to their initial CSF HIV RNA escape. Clinicians should be vigilant of relapse of symptoms, particularly when simplifying ART regimens in people with CSF HIV RNA escape., (© 2023 British HIV Association.)

Introduction: Expanding HIV pre-exposure prophylaxis (PrEP) use is key to goals for lowering new HIV infections in the U.S. by 90% between 2022 and 2030. Unfortunately, youth aged 16-24 have the lowest PrEP use of any age group and the highest HIV incidence rates., Methods: To examine the relationship between HIV seroconversion and PrEP uptake, adherence, and continuity, we used survival analysis and multivariable logistic regression on data of 895 youth at-risk for HIV infection enrolled in Adolescent Trials Network for HIV Medicine protocol 149 in Los Angeles and New Orleans, assessed at 4-month intervals over 24 months., Results: The sample was diverse in race/ethnicity (40% Black, 28% Latine, 20% White). Most participants (79%) were cis-gender gay/bisexual male but also included 7% transgender female and 14% trans masculine and nonbinary youth. Self-reported weekly PrEP adherence was high (98%). Twenty-seven participants acquired HIV during the study. HIV incidence among PrEP users (3.12 per 100 person year [PY]) was higher than those who never used PrEP (2.53/100 PY). The seroconversion incidence was highest among PrEP users with discontinuous use (3.36/100 PY). If oral PrEP users were adherent using 2-monthly long-acting injectables, our estimate suggests 2.06 infections per 100 PY could be averted., Conclusions: Discontinuous use of PrEP may increase risk of HIV acquisition among youth at higher risk for HIV infection and indications for PrEP. Thus, to realize the promise of PrEP in reducing new HIV infections, reducing clinical burdens for PrEP continuation are warranted., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance., Methods: We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models., Findings: We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance., Interpretation: Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART., Funding: US National Institutes of Health, Swiss National Science Foundation., Competing Interests: Declaration of interests SMI reports grant funding from the US National Institutes of Health (NIH) National Institute on Alcohol Abuse and Alcoholism for the work of ART-CC (payment to institution). AvS reports funding from the Dutch Ministry of Health, Welfare and Sport for the maintenance of the ATHENA database, and grant funding from the European Centre for Disease Prevention and Control (payment to institution). MJG reports honoraria as an ad-hoc member of HIV National Advisory Boards from Merck, Gilead Sciences, and ViiV, and a leadership position as Medical Director of the Southern Alberta HIV Clinic. CAS has received funding from Gilead Sciences, ViiV Healthcare, and Janssen-Cilag for membership of Data Safety and Monitoring Committees and Advisory Committees and for preparation of educational material. HFG has received personal fees from Merck, Gilead Sciences, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis, as an advisor or consultant or for Data Safety Monitoring Board membership, and has received a travel grant from Gilead. JACS reports funding for research in this publication from the NIH National Institute on Alcohol Abuse and Alcoholism (payment to institution), UK National Institute for Health and Care Research (payment to institution), and the University of Bern (payment to institution). RL reports support for research in this publication by the NIH National Institute of Allergy and Infectious Diseases under award number R01AI152772, and support from the NIH National Institute of Allergy and Infectious Diseases under award number R01AI167699 for a separate project pertaining to HIV treatment strategies. ME reports funding for research in this publication from the Swiss National Science Foundation (32FP30-18949) and the NIH (Cooperative Agreement AI069924 and R01 AI152772-01). RDK reports funding for research in this publication from the Swiss National Science Foundation and the NIH National Institute of Allergy and Infectious Diseases, and reports grant funding from Gilead Sciences. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The rise of HIV-1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) threatens the long-term success of NNRTI-based therapies. Our study aims to describe the circulation of major resistance-associated mutations (RAMs) for NNRTIs in people living with HIV (PLWH) in Italy from 2000 to 2020. We included 5982 naïves and 28 505 genotypes from 9387 treatment-experienced PLWH from the Antiviral Response Cohort Analysis (ARCA) cohort. Transmitted drug resistance (TDR) was found in 12.5% and declined from 17.3% in 2000-2003 to 10.9% in 2016-2020 (p = 0.003). Predictors of TDR were viral subtype B [vs. non-B, adjusted odds ratio (aOR) = 1.94, p < 0.001], zenith viral load (VL) (per 1 log 10 higher, aOR = 0.86, p = 0.013), nadir CD4 cell count (per 100 cells/μL increase aOR = 0.95, p = 0.013). At least one RAM for NNRTIs among treatment experienced PLWH was detected in 33.2% and pre-treatment drug resistance (PDR) declined from 43.4% in 2000-2003 to 20.9% in 2016-2020 (p < 0.001). Predictors of PDR were sexual transmission route (vs. others, aOR = 0.78, p < 0.001), time since HIV diagnosis (per 1 month longer, aOR = 1.002, p < 0.001), viral subtype B (vs. non B, aOR = 1.37, p < 0.001), VL (per 1 log 10 higher, aOR = 1.12, p < 0.001), nadir CD4 count (per 100 cells/μL increase, aOR = 0.91, p < 0.001), previous exposure to any NNRTI (aOR = 2.31, p < 0.001) and a more recent calendar year sequence (any time span > 2008 vs. 2000-2003, any aOR <1, p < 0.001). Circulation of RAMs to NNRTIs declined during the last 20 years in Italy. NNRTIs remain pivotal drugs for the management of HIV-1 due to safety concerns and long-acting options., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: We sought to evaluate the variability of HIV-1 and its effect on immuno-virological response among adolescents living with perinatally acquired HIV (APHI)., Methods: A cohort study was conducted from 2018-2020 among 311 APHI receiving antiretroviral therapy (ART) in Cameroon. Sequencing of protease and reverse transcriptase regions was performed for participants experiencing virological failure, VF, (Plasma viral load, PVL ≥ 1000 RNA copies/ml). HIV-1 subtypes were inferred by phylogeny; immuno-virological responses were monitored at 3-time points (T1-T3). Cox regression modeling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4 < 250, and PVL > 5log10, adjusted for acquired drug resistance, gender, ART line, adherence, and duration on treatment; p < 0.05 was considered statistically significant., Results: Of the 141 participants in VF enrolled, the male-female ratio was 1:1; mean age was 15 (±3) years; and median [IQR] duration on ART was 51 [46-60] months. In all phases, 17 viral clades were found with a predominant CRF02&#95;AG (58.2%, 59.4%, and 58.3%). From T1-T3 respectively, there was an increasing CD4 count (213 [154-313], 366 [309-469], and 438 [364-569] cells/mm3) and decline log10 PVL (5.23, 4.43, and 4.43), similar across subtypes. Among participants with CRF02&#95;AG infection, duration of treatment was significantly associated with both rates of progression to CD4 < 250, and PVL > 5log10, aHR = 0.02 (0.001-0.52), and aHR = 0.05 (0.01-0.47) respectively. Moreover, four potential new HIV-1 recombinants were identified (CRF02&#95;AG/02D, CRF02&#95;AG/02A1F2, D/CRF02&#95;AG, and AF2/CRF02&#95;AG), indicating a wide viral diversity., Conclusion: Among APHI in settings like Cameroon, there is a wide genetic diversity of HIV-1, driven by CRF02&#95;AG and with potential novel clades due to ongoing recombination events. Duration of treatment significantly reduces the risk of disease progression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Togna Pabo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Ethiopia is among the highly HIV-affected countries, with reported 12,000 and 12,000 AIDS-related deaths and incidents as per reports from 2021. Although the country has made a promising progress in antiretroviral therapy, recent studies have indicated that pretreatment drug resistance (PDR) is alarmingly increasing, which has become a challenge for the effectiveness of HIV treatment. Epidemiologic data on PDR is necessary to help establish ART regimens with good efficacy. Thus, this systematic review aimed to determine the trend analysis of PDR among ART-naïve individuals along with HIV variant dynamics in Ethiopia., Method: HIV-1 pol sequences from studies conducted between 2003 and 2018 among ART-naïve Ethiopian individuals were retrieved from GenBank and analyzed for the presence of PDR mutations (PDRM) along with the analysis of HIV-1 variant dynamics. The Calibrated Population Resistance (CPR) tool Version 8.1 and the REGA HIV-1 Subtyping Tool Version 3 were used to determine the PDRM and HIV-1 genetic diversity, respectively., Result: We identified nine studies and analyzed 1070 retrieved HIV-1 pol sequences in this systematic review. The pooled prevalence of PDR was 4.8% (51/1070), including 1.4% (15/1070), 2.8% (30/1070), and 0.8% (9/1070) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI), and protease inhibitor (PI) resistance, respectively. NRTI and NNRTI concurrent PDRM were observed among 0.2% (2/799) of the analyzed sequences. The overall PDR prevalence has been increasing over the years. Though the prevalence of the NNRTI, NRTI, and PI PDR also increased over the years, the NNRTI increment was more pronounced than the others, reaching 7.84% in 2018 from 2.19% in 2003. The majority (97%; 1038/1070) of the genetic diversity was HIV-1 subtype C virus, followed by subtype C' (2%; 20/1038) and other subtypes (1%; 10/1038)., Conclusions: According to this systematic review, the overall pooled prevalence of PDR is low. Despite the low prevalence, there has been an increasing trend of PDR over the years, which implies the need for routine surveillance of PDRMs along with preventive measures. Hence, this supports the recently endorsed transition of ART regimens from NNRTI to integrase strand transfer inhibitor-based regimens recommended by the WHO. In addition, this finding underscores the need for routine baseline genotypic drug resistance testing for all newly diagnosed HIV-infected patients before initiating treatment to halt the upward trend of PDR., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals in Sub Saharan Africa, including Uganda. Isoniazid prophylaxis therapy (IPT) is a major public health intervention to limit tuberculosis disease among people living with HIV. However, there is limited information about the influence of IPT on TB disease incidence and its associated risk factors among HIV positive patients in Uganda especially at Reach out-Mbuya community health initiative hence the study. A cross sectional study was conducted among HIV positive adult patients who completed a 6-months long daily treatment of Isoniazid preventive therapy. Sputum samples and urine samples were collected and analysed using Gene Xpert and lateral flow urine Lipoarabinomannan (LF-LAM) tests respectively for presence of Tuberculosis disease. Data analysis was performed using STATA (version 14). Bivariate and multivariate logistic regression were performed to assess the risk factors associated with tuberculosis among the study population and significance estimated at 95% confidence level. A total of 103 HIV positive adults was studied. The mean age of the participants was 42.1 (10.5) and median age was 43 (IQR = 16). The prevalence of tuberculosis disease among HIV positive adult patients who completed Isoniazid preventive therapy was 5.8% (6/103). Counselling, the only significant factor, reduced the likelihood of occurrence of TB disease among HIV patients on IPT treatment (aOR:0.028, P-value < 0.001). A low prevalence of TB disease was observed among HIV patients on IPT treatment. Counselling is a protective factor of TB disease among HIV patients on IPT treatment., (© 2023. Springer Nature Limited.)

Background: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy., Methods: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization., Results: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52)., Conclusions: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.)., (Copyright © 2023 Massachusetts Medical Society.)

'Kick and kill' cure strategies aim to induce HIV protein expression in latently infected cells (kick), and thus trigger their elimination by cytolytic T cells (kill). In the Research in Viral Eradication of HIV Reservoirs trial (NCT02336074), people diagnosed with primary HIV infection received immediate antiretroviral therapy (ART) and were randomised 24 weeks later to either a latency-reversing agent, vorinostat, together with ChAdV63.HIVconsv and MVA.HIVconsv vaccines, or ART alone. This intervention conferred no reduction in HIV-1 reservoir size over ART alone, despite boosting virus-specific CD4+ and CD8+ T cells. The effects of the intervention were examined at the cellular level in the two trial arms using unbiased computational analysis of polyfunctional scores. This showed that the frequency and polyfunctionality of virus-specific CD4+ and CD8+ T cell populations were significantly increased over 12 weeks post-vaccination, compared to the ART-only arm. HIV-specific IL-2-secreting CD8+ T cells also expanded significantly in the intervention arm and were correlated with antiviral activity against heterologous HIV in vitro. Therapeutic vaccination during ART commenced in primary infection can induce functional T cell responses that are phenotypically similar to those of HIV controllers. Analytical therapy interruption may help determine their ability to control HIV in vivo., (© 2023. Springer Nature Limited.)

Objectives: Pre-existing rilpivirine resistance-associated mutations (RVP-RAMs) have been found to predict HIV-1 virological failure in those switching to long-acting injectable cabotegravir/rilpivirine. We here evaluated the prevalence of archived RPV-RAMs in a cohort of people living with HIV (PWH)., Methods: We analysed near full-length HIV-1 pol sequences from proviral DNA for the presence of RPV-RAMs, which were defined according to the 2022 IAS-USA drug resistance mutation list and Stanford HIV drug resistance database., Results: RPV-RAMs were identified in 757/5805 sequences, giving a prevalence of 13.0% (95% CI 12%-13.9%). Amongst the ART-naive group, 137/1281 (10.7%, 95% CI 9.1%-12.5%) had at least one RPV-RAM. Of the 4524 PWH with viral suppression on ART (VL <400 copies/mL), 620 (13.7%, 95% CI 12.7%-14.7%) had at least one RPV-RAM. E138A was the most prevalent RPV-RAM in the ART-naive group (7.9%) and the ART-suppressed group (9.3%). The rest of the mutations observed (L100I, K101E, E138G, E138K, E138Q, Y181C, H221Y, M230L, A98G, V179D, G190A, G190E and M230I) were below a prevalence of 1%., Conclusions: RPV-RAMs were present in 10.7% of ART-naive and 13.7% of ART-suppressed PWH in Botswana. The most common RPV-RAM in both groups was E138A. Since individuals with the E138A mutation may be more likely to fail cabotegravir/rilpivirine, monitoring RPV-RAMs will be crucial for effective cabotegravir/rilpivirine implementation in this setting., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

In this study, a total of 462 samples of whole blood were collected from 36 patients enrolled. During the entire course of antiretroviral therapy (ART) from 2003 to 2019, both the CD4 cell count and viral load (VL) of study patients were examined annually, and an HIV-1 genotypic drug resistance (DR) assay was carried out using an in-house method when the HIV-1 VL was >1,000 copies/mL. The results indicated that 13 (36.1%) experienced treatment failure and 23 (63.9%) experienced treatment success among 36 patients. The proportion of patients with effective treatment after the adjustment of ART regimens was significantly higher than before adjustment (χ 2  = 33.796, p  < .001). Furthermore, the frequencies of HIV-1 DR mutations before adjustment were higher than those after adjustment ( t  = 3.345, p  = .002). In particular, among 23 patients with effective treatment after adjustment, the means ± standard deviations of the VLs and CD4 cell counts before adjustment were 3.85 ± 0.65 log RNA copies/mL and 226.83 ± 106.06 cells/mm 3 , respectively, compared with 2.19 ± 0.58 log RNA copies/mL and 367.68 ± 174.62 cells/mm 3 , respectively, after adjustment. Obviously, there were statistically significant differences in the changes in VL ( t  = 8.728, p  < .001) and CD4 cell count ( t  = -4.476, p  < .001) before and after adjustment. Therefore, patients who received updated ART regimens containing LPV/r and TDF after adjustment achieved better therapeutic effects compared with patients who received initial ART regimens harboring D4T/AZT or NVP. This suggests that future research is needed to initiate the surveillance of DR, VLs, and CD4 cell counts immediately after HIV diagnosis, and dynamic changes in these indicators so as to optimize ART effects.

The objective was to evaluate outcomes in a heroin-dependent population 35 years after first enrolment in methadone maintenance treatment (MMT).  An ad hoc protocol was used to assess drug misuse, treatment, and drug-related morbidity in the survivor sample. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated.  A total of 214 heroin-dependent patients entered MMT between 1982 and 1984 in the Asturias Public Health Service. Information was received on 195 subjects, of whom 146 were deceased.  Men accounted for 77.5% of the study cohort. Over the 35-year follow-up period, the SMR was 11.75 (95% CI = 9.95 - 13.77). In the survivor sample, 5.7% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 38.77% and hepatitis B/C in 73.46%. No differences were found between sexes in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 35-year follow-up compared with 5.26% of males. In conclusion, our study confirms the high long-term mortality rate of heroin addicts, even after enrollment in MMT.

Background: Cabotegravir plus rilpivirine is the only approved complete long-acting regimen for the maintenance of HIV-1 virological suppression dosed every 2 months. The SOLAR study aimed to compare long-acting cabotegravir plus rilpivirine every 2 months with continued once-daily bictegravir, emtricitabine, and tenofovir alafenamide for the maintenance of HIV-1 virological suppression in adults living with HIV., Methods: SOLAR is a randomised, open-label, multicentre, phase 3b, non-inferiority study. The study was done in 118 centres across 14 countries. Participants with HIV-1 RNA less than 50 copies per mL were randomly assigned (2:1), stratified by sex at birth and BMI, to either long-acting cabotegravir (600 mg) plus rilpivirine (900 mg) dosed intramuscularly every 2 months or to continue daily oral bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants randomly assigned to long-acting therapy had a choice to receive cabotegravir (30 mg) plus rilpivirine (25 mg) once daily as an optional oral lead-in for approximately 1 month. The primary efficacy endpoint was the proportion of participants with virological non-response (HIV-1 RNA ≥50 copies per mL; the US Food and Drug Administration snapshot algorithm, 4% non-inferiority margin; modified intention-to-treat exposed population) at month 11 (long-acting start with injections group) and month 12 (long-acting with oral lead-in group and bictegravir, emtricitabine, and tenofovir alafenamide group). The study is registered with ClinicalTrials.gov, NCT04542070, and is ongoing., Findings: 837 participants were screened between Nov 9, 2020, and May 31, 2021, and 687 were randomly assigned to switch treatment or continue existing treatment. Of 670 participants (modified intention-to-treat exposed population), 447 (67%) switched to long-acting therapy (274 [61%] of 447 start with injections; 173 [39%] of 447 with oral lead-in) and 223 (33%) continued bictegravir, emtricitabine, and tenofovir alafenamide. Baseline characteristics were similar; median age was 37 years (range 18-74), 118 (18%) of 670 were female sex at birth, 207 (31%) of 670 were non-White, and median BMI was 25·9 kg/m 2 (IQR 23·3-29·5). At month 11-12, long-acting cabotegravir plus rilpivirine showed non-inferior efficacy versus bictegravir, emtricitabine, and tenofovir alafenamide (HIV-1 RNA ≥50 copies per mL, five [1%] of 447 vs one [<1%] of 223), with an adjusted treatment difference of 0·7 (95% CI -0·7 to 2·0). Excluding injection site reactions, adverse events and serious adverse events were similar between groups. No treatment-related deaths occurred. More long-acting group participants had adverse events leading to withdrawal (25 [6%] of 454 vs two [1%] of 227). Injection site reactions were reported by 316 (70%) of 454 long-acting participants; most (98%) were grade 1 or 2., Interpretation: These data support the use of long-acting cabotegravir plus rilpivirine dosed every 2 months as a complete antiretroviral regimen that has similar efficacy to a commonly used integrase strand transfer inhibitor-based first-line regimen, while addressing unmet psychosocial issues associated with daily oral treatment., Funding: ViiV Healthcare., Competing Interests: Declaration of interests MNR reports consulting fees from Merck, Gilead, ViiV Healthcare, and Janssen, and honoraria from AbbVie, Gilead, ViiV Healthcare, and Janssen. RD reports owning stock in Gilead, GSK, BMS, Pfizer, Merck, and Janssen, and financial support for research from Merck, Gilead, ViiV Healthcare, and Janssen. SO reports research grants from ViiV Healthcare and Gilead Sciences, honoraria from ViiV Healthcare, Gilead, and MSD, and participation in advisory boards for ViiV Healthcare. SW reports funding for investigator-initiated clinical trials from Merck, ViiV Healthcare, Gilead, and Janssen, consulting fees from Merck and ViiV Healthcare, honoraria from Merck, ViiV Healthcare, and Gilead, and is the Co-Director of the Canadian HIV Trials Network. GDP reports consulting fees from AbbVie, GS Pharma, Merck, Janssen, ViiV Healthcare, Pfizer, Roche, AstraZeneca, and Atea Pharmaceuticals, honoraria from AbbVie, GS Pharma, Merck, Janssen, ViiV Healthcare, Pfizer, and AstraZeneca, and participation in advisory boards for AbbVie, GS Pharma, Merck, Janssen, ViiV Healthcare, Pfizer, Roche, AstraZeneca, and Atea Pharmaceuticals. KSu, DS-P, CLL, RD'A, MPB, PP, VC, WRS, HPG, KSm, and JvW are employees of ViiV Healthcare and stockholders of GSK. AB and FZ are employees and stockholders of GSK. RVS-R and VVE are employees and stockholders of Janssen. AC, CC, OO, VD-B, and JS declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Data on human immunodeficiency virus (HIV) seroconversion among men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) in West Africa are needed. This study aimed to document HIV seroconversion and associated determinants, PrEP adherence, plasma drug concentrations, and HIV drug resistance in MSM using event-driven or daily PrEP in Burkina Faso, Côte d'Ivoire, Mali, and Togo., Methods: A prospective cohort study was conducted in 2017-2021 among HIV-seronegative MSM aged 18 or over who were at high risk of HIV infection. Participants could choose between event-driven and daily PrEP, switch regimens, and discontinue or restart PrEP. The determinants of HIV incidence were investigated using a multivariate mixed-effects Poisson regression analysis., Results: A total of 647 participants were followed for a total time of 1229.3 person-years. Of 5371 visits, event-driven PrEP was chosen in 3873 (72.1%), and daily PrEP in 1400 (26.1%). HIV incidence was 2.4 per 100 person-years (95% confidence interval [CI] 1.5-3.6) for event-driven PrEP, and 0.6 per 100 person-years (95% CI .1-2.3) for daily PrEP (adjusted incidence rate ratio 4.40, 95% CI 1.00-19.36, P = .050). Adequate adherence was lower with event-driven than daily PrEP (44.3% vs 74.9%, P < .001). Plasma drug concentrations were undetectable in 92 (97.9%) of the 94 measures taken for 23 participants who seroconverted. Only 1 participant had resistance to PrEP drugs., Conclusions: HIV seroconversions mainly occurred in participants who chose event-driven PrEP. The study's data highlighted major difficulties with adherence to this regimen. Improving adherence to event-driven PrEP constitutes a major research and public health priority in this context., Competing Interests: Potential conflicts of interest. G. P. has received travel grants or contracts, fees for conferences, and consultancy fees from various pharmaceutical companies, including Gilead Sciences, MSD France, Pfizer, Takeda, and ViiV Healthcare. G. P. also reports participation in Data Safety Monitoring or Advisory Boards for Gilead Sciences and ViiV Healthcare. C. L. has received a travel grant and fees for a meeting from Gilead Sciences. 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) 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.)

Background: Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions., Case Presentation: A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient's immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm 3 (30-35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy., Conclusion: The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Tuberculosis (TB) is a chronic respiratory infection. Co-infection with human immunodeficiency virus (HIV) has been a significant obstacle to TB control. Insufficient attention has been given to TB/HIV, and more information is needed to address this issue. We conducted an observational study to investigate the epidemiological characteristics, treatment outcomes and its associated factors of HIV-positive TB patients in Southeast China., Methods: An observational study was conducted based on data collected directly from China National TB Surveillance System during 2012-2021. Epidemiological characteristics, drug resistance and outcomes were described as frequency (n) and percentage (%). Risk factors for unsuccessful outcomes were determined using univariate (chi-squared) and multivariate logistic regression analysis., Results: A total of 347 TB/HIV cases were included, and the proportion of HIV-positive cases among all TB cases increased significantly from 0.06% to 2012 to 0.40% in 2021. The majority of cases were males (86.5%), non-local household registers (139, 40.1%), farmers or workers (179, 51.6%), and aged 40-59 (142, 40.9%). Of 347 cases, 290 (83.6%) had pulmonary TB (PTB), 10 (2.9%) had extra pulmonary TB (EPTB) and 47(13.5%) had both PTB and EPTB. A total A total of 258 (74.4%) were HIV positive prior to TB diagnosis. 8.0% (4/50) of cases were resistant to rifampicin (RIF) and 274 patients (83.8%) had successful outcomes. Being non-local (AOR = 2.193, 95% CI = 1.196-4.022, P = 0.011) and diagnosed HIV infection after TB (AOR = 2.365, 95% CI = 1.263-4.430, P = 0.007) were independent risk factors for unsuccessful outcomes of anti-TB treatment., Conclusion: During 2012-2021, the proportion of HIV-positive cases among all TB cases increased significantly in Southeast China. HIV-positive TB patients were significantly more likely to develop resistance to RIF and INH and unsuccessful anti-TB treatment. Non-local registration and becoming HIV positive after TB diagnosis were independent risk factors associated with unsuccessful outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The NNRTI doravirine has been recently approved for the first-line treatment of HIV-infected patients, eliciting favourable responses against viruses bearing the K103N, Y181C and G190A mutations. This study used in vitro drug selections to elaborate the breadth of doravirine responses against viruses bearing NNRTI and NRTI resistance-associated mutations (RAMs)., Methods: WT clinical isolates (n = 6) and viruses harbouring common NRTI and NNRTI RAMs (n = 6) were serially passaged in escalating concentrations of doravirine, doravirine/islatravir, doravirine/lamivudine and rilpivirine over 24 weeks. Genotypic analysis ascertained the appearance and accumulation of NNRTI RAMs. Phenotypic drug susceptibility assays assessed resistance conferred by acquired NNRTI RAMs., Results: For WT viruses, doravirine pressure led to the appearance of V108I or V106A/I/M RAMs after 8 weeks, conferring low-level (∼2-fold) resistance. After 24 weeks, the accumulation of three to six secondary RAMs, including F227L, M230L, L234I and/or Y318, resulted in high-level (>100-fold) resistance to doravirine. Notably, viruses with these doravirine RAMs remained susceptible to rilpivirine and efavirenz. This contrasted with rilpivirine where acquisition of E138K, L100I and/or K101E resulted in >50-fold cross-resistance to all NNRTIs. Doravirine selection of viruses bearing common NRTI and NNRTI RAMs showed delayed acquisition of RAMs compared with WT virus. Pairing doravirine with islatravir or lamivudine attenuated the development of NNRTI RAMs., Conclusions: Doravirine showed favourable resistance profiles against viruses harbouring NRTI and NNRTI RAMs. The high barrier to resistance to doravirine coupled with the long intracellular half-life of islatravir may provide the opportunity for long-acting treatment options., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Most HIV cure studies remain in the early stage of investigation and may carry clinical risks to the participants and, in some cases, their partners. Surprisingly little sociobehavioral research has investigated the perceptions of couples-including HIV serodifferent couples-around HIV cure research, including factors that would influence recruitment and retention in trials. We conducted a qualitative study to explore perceptions of diverse HIV serodifferent partners in the United States. We recruited 10 diverse HIV serodifferent couples (20 participants). We found participants had learned to cope with the reality of HIV, including protections during sex, and ascribed both positive and negative meanings to an HIV cure. Partners expressed concern about each other's health and potentially caring for a sick partner and emphasized the importance of safety when participating in an HIV cure trial. They identified the need for partner protection measures during analytical treatment interruptions (ATIs) as an ethical imperative. Participants recounted experiences of HIV stigma due to being in HIV serodifferent relationships and viewed ATIs as leading to a detectable viral load, which could limit sexual expression, complicate disclosure decision making, and worsen HIV-related stigma. Our study's main contribution is to inform efforts to meaningfully engage diverse HIV serodifferent partners in HIV cure research in the United States. Our data suggest people with HIV make decisions to participate in research based on close ones in their life and underscore the critical importance of acknowledging relationship dynamics in decisions to participate in research.

At present, research on the prevalence of primary drug resistance (PDR) in Hunan Province is limited. Therefore, we explored the current status of HIV-1 PDR in Hunan to provide a basis for antiretroviral therapy (ART) and a theoretical foundation for prevention and control of the HIV/AIDS epidemic. Three hundred seventy newly diagnosed HIV-1-infected individuals who had not received ART in Hunan province, China, were enrolled in the study. Plasma samples were collected, RNA was extracted, two rounds of gene amplification were carried out with the in-house method, and subtype analysis and drug resistance analysis were carried out with relevant software. We found that the most prevalent subtypes of HIV-1 in Hunan Province are CRF&#95;01AE (126/359, 35.1%) and CRF07&#95;BC (85/359, 23.7%). The PDR rate among newly diagnosed HIV/AIDS patients was 10.0% (36/359). Among them, the drug resistance rates of protease inhibitors, nucleotide reverse transcriptase inhibitors, non-nucleotide reverse transcriptase inhibitors, and integrase inhibitors were 0.3% (1/359), 3.3% (12/359), 8.36% (30/359), and 0.6% (2/359), respectively. The distribution of HIV-1 subtypes in Hunan Province is diverse and complex, and the PDR rate has exceeded the low-level warning line set by the World Health Organization (<5%). Therefore, we should conduct pretreatment drug resistance assays to determine the optimal primary ART so that patients can obtain better antiretroviral treatment outcomes and transmission of drug-resistant strains in the population can be blocked.

Background: In French Guiana (population 294,000) the prevalence of type 2 diabetes (10%) and of HIV(1.1%) are very high. Our objective was to determine the prevalence of diabetes and its complications in a HIV cohort., Materials and Methods: We enrolled HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals between January 1, 1992 and December 31, 2021 in the French Hospital Database for HIV (FHDH) a national database compiling data from all French regions., Results: There was no difference of diabetes prevalence between men (8.2%) and women (8.8%), P = 0.4. Patients with diabetes were older (56 years ± 13.4) than those without diabetes (44.7 years ± 13.6) and prevalence increased with age. The proportion of persons with diabetes was greater among virologically suppressed persons (10%) than those with a detectable viral load under antiretroviral treatment (5.8%). Persons with diabetes had substantially greater CD4 counts at diagnosis than persons without diabetes. The majority of macro and microvascular complications were observed in people with diabetes. Persons with diabetes and HIV were significantly less likely to have had AIDS (1.6 versus 2.2 per 100 person-years, respectively). Overall, 374 persons living with HIV of 4167 had died (9%) the proportion of persons with diabetes among the dead was greater than those who did not die 11.7% versus 8.1%, respectively, p = 0.017. However, persons with diabetes were older and hence died older, 62.3 years (SD = 1.9) for deceased persons with diabetes versus 50.4 years (SD = 0.8), P < 0.0001. However, using Cox regression to adjust for age, initial CD4 count, country of birth there was no significant difference in the Hazard for death between persons with diabetes and persons without diabetes (aHR = 0.99, 95%CI = 0.65-1.5), P = 0.9., Conclusions: The prevalence of diabetes in our HIV cohort was high. Persons with diabetes had greater CD4 counts, earlier care, and greater virological suppression than persons without diabetes. There were no significant differences between persons with diabetes and without diabetes in terms of survival., (© 2023. The Author(s).)

Background: Panzi General Reference Hospital (HGR Panzi) in the Democratic Republic of Congo follows a large number of patients living with HIV-1 (PLWHIV). Although antiretrovirals (ARVs) are available, HIV-1 viral load (HIV-VL) measurement has only been implemented in the hospital since 2018. No data on ARV resistance levels and ARV dosage in plasma have yet been published for this region. We determined the prevalence of virological failure due to ARV resistance amongst patients and assessed the degree of genotypic resistance of the viral strains., Methods: We performed an HIV-VL test and determined dosage of ARVs on samples collected from 205 PLWHIV at HGR Panzi between 2017 and 2018, including 13 ARV-naive patients. Genotypic resistance testing was performed on all samples with detectable HIV-VLs, and interpreted with the Agence Nationale de Recherches sur le Sida (ANRS) 2018 algorithm., Results: Baseline resistance to NNRTIs was found in 2 of the 13 treatment-naive individuals (15%). ARV dosage was non-optimal for 44/192 of treated patients (22.9%), with an HIV-VL ≥1000 IU/mL for 40/192 (20.8%) of them. In particular, treatment-experienced viruses presented resistance to at least one NRTI (52.5%), to at least one NNRTIs (70%) or to at least one PIs (15%). Finally, two samples contained viruses with resistance polymorphism in the integrase gene., Conclusions: The high level of resistance to ARVs observed during this study, mainly due to treatment compliance default, fully justifies the implementation of means for closer patient monitoring. The provision of VL tests and therapeutic education management tools in a PLWHIV follow-up remains an absolute necessity to best adapt the current treatment lines in this region., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, we investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data., Methods: The case-control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study. We measured VRC01 serum concentrations with a qualified pharmacokinetic (PK) Binding Antibody Multiplex Assay. We employed nonlinear mixed effects PK modelling to estimate daily-grid VRC01 concentrations. Cox regression models were used to assess the association of VRC01 concentration at exposure and baseline body weight, with the hazard of HIV-1 acquisition and prevention efficacy as a function of VRC01 concentration. We also compared fixed dosing vs. body weight-based dosing via simulations., Findings: Estimated VRC01 concentrations in VRC01 recipients without HIV-1 were higher than those in VRC01 recipients who acquired HIV-1. Body weight was inversely associated with HIV-1 acquisition among both placebo and VRC01 recipients but did not modify the prevention efficacy of VRC01. VRC01 concentration was inversely correlated with HIV-1 acquisition, and positively correlated with prevention efficacy of VRC01. Simulation studies suggest that fixed dosing may be comparable to weight-based dosing in overall predicted prevention efficacy., Interpretation: These findings suggest that bnAb serum concentration may be a useful marker for dosing regimen selection, and operationally efficient fixed dosing regimens could be considered for future trials of HIV-1 bnAbs., Funding: Was provided by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (UM1 AI068614, to the HIV Vaccine Trials Network [HVTN]; UM1 AI068635, to the HVTN Statistical Data and Management Center [SDMC], Fred Hutchinson Cancer Center [FHCC]; 2R37 054165 to the FHCC; UM1 AI068618, to HVTN Laboratory Center, FHCC; UM1 AI068619, to the HPTN Leadership and Operations Center; UM1 AI068613, to the HIV Prevention Trials Network [HPTN] Laboratory Center; UM1 AI068617, to the HPTN SDMC; and P30 AI027757, to the Center for AIDS Research, Duke University (AI P30 AI064518) and University of Washington (P30 AI027757) Centers for AIDS Research; R37AI054165 from NIAID to the FHCC; and OPP1032144 CA-VIMC Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests Kelly E Seaton - support for meetings, HIV Vaccine Trials Network (HVTN). M Julianna McElrath - support for Keystone Symposia. Ian Frank - consulting fees from Gilead, ViiV Health Care and grants or contracts from Moderna, Janssen Therapeutics, Pfizer., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans., Methods: Genetic sub-study of adults randomized to initiate TAF or TDF together with dolutegravir and emtricitabine was conducted. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine β2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations., Results: 336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 ( P  = 0.022), ABCC10 rs2125739 ( P  = 0.07), and ABCC4 rs1059751 ( P  = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 ( P  = 0.0013), rs691857 ( P  = 0.00039), and PKD2 rs72659631 ( P  = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 ( P  = 3.4 × 10 -9 ), CDH4 rs66494466 ( P  = 5.6 × 10 -8 ), and ITGA4 rs3770126 ( P  = 6.1 × 10 -7 )., Conclusion: Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Antiretroviral therapy has revolutionized HIV treatment, increasing quality and life expectancy of people living with HIV (PLWH). However, the expansion of treatment has resulted in an increase in antiretroviral-resistant viruses, which can be an obstacle to maintenance of successful ART., Objectives: This study analysed the genetic composition of the HIV near full-length genome (NFLG) from archived proviruses of PLWH under successful ART, and determined the presence/frequency of drug resistance mutations (DRMs) and viral subtype., Patients and Methods: Forty-six PLWH from Rio de Janeiro (RJ) and 40 from Rio Grande (RS) had proviral HIV NFLG PCR-amplified and ultradeep sequenced. The presence/frequency of DRMs were analysed in Geneious. Phylogenetic analyses were performed using PhyML and SimPlot., Results: All samples included in the study were sequenced and 69 (80.2%) had the HIV NFLG determined. RJ and RS showed a predominance of HIV subtypes B (78.3%) and C (67.5%), respectively. Overall, 168 DRMs were found in 63 (73.3%) samples, and 105 (62.5%) of them were minority variants. Among DRMs, 41 (39.0%) minority variants and 33 (52.4%) variants with frequency above 20.0% in the viral population were able to confer some degree of resistance to at least one drug in use by respective patients, yet no one showed signs of therapeutic failure., Conclusions: Our study contributes to the understanding of the impact of DRMs on successful therapy and supports the sustainability of combinatorial ART, because all patients maintained their successful treatment despite the high prevalence of DRMs at low (62.5%) or high (37.5%) frequency., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. 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.