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The development of ribosomal profiling (Riboseq) revealed the immense coding capacity of human and viral genomes. Here, we used Riboseq to delineate the translatome of HIV-1 in infected CD4 + T cells. In addition to canonical viral protein coding sequences (CDSs), we identify 98 alternative open reading frames (ARFs), corresponding to small Open Reading Frames (sORFs) that are distributed across the HIV genome including the UTR regions. Using a database of HIV genomes, we observe that most ARF amino-acid sequences are likely conserved among clade B and C of HIV-1, with 8 ARF-encoded amino-acid sequences being more conserved than the overlapping CDSs. Using T cell-based assays and mass spectrometry-based immunopeptidomics, we demonstrate that ARFs encode viral polypeptides. In the blood of people living with HIV, ARF-derived peptides elicit potent poly-functional T cell responses mediated by both CD4 + and CD8 + T cells. Our discovery expands the list of conserved viral polypeptides that are targets for vaccination strategies and might reveal the existence of viral microproteins or pseudogenes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Prevention of cardiovascular disease is a major issue in the current management of people living with HIV. Concern is growing about the metabolic impact of integrase strand transfer inhibitors (INSTIs), which could lead to an increased risk of diabetes, but the data are conflicting. This is an updated version of our previous analysis, with longer follow-up and new molecules., Methods: We retrospectively evaluated the incidence of new-onset diabetes in people living with HIV starting combined antiretroviral therapy with an INSTI compared with non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Data were collected from the Dat'AIDS cohort study, a collaboration of 30 HIV treatment centres in France. We used a propensity score-based inverse probability of treatment weighting approach to adjust for baseline characteristics between the two groups (INSTI and non-INSTI)., Results: Between 2009 and 2021, a total of 12 150 people living with HIV were included. The incidence of diabetes was higher in the INSTI group than in the non-INSTI group (hazard ratio 1.38; 95% confidence interval 1.07-1.77; p = 0.012). Regardless of the third drug, but to a greater extent for INSTIs, we observed a peak of new-onset diabetes in the year following initiation of combined antiretroviral therapy., Conclusions: The incidence of diabetes was higher in people treated with integrase inhibitors than in those receiving other third agents. This increased risk occurred both during the first year of treatment and in the longer term., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Patient-reported outcomes (PROs) facilitate communication between patients and providers, enhancing patient-centered care. We report PROs for virologically suppressed people living with HIV-1 who switched to dolutegravir/lamivudine (DTG/3TC) or continued their 3- or 4-drug current antiretroviral regimen (CAR) in the phase 3 SALSA study. Secondary endpoints included change from baseline in HIV Treatment Satisfaction Questionnaire (status version; HIVTSQs) and HIV Symptom Distress Module (HIV-SDM) at Weeks 4, 24, and 48. A post hoc analysis assessed change in HIVTSQs and HIV-SDM by age (≥ 50 and < 50 years). Higher HIVTSQs scores represent greater treatment satisfaction (range, 0-60); lower HIV-SDM scores indicate less symptom bother (range, 0-80). Participants in the DTG/3TC (n = 246) and CAR (n = 247) groups reported comparable baseline HIVTSQs total scores (mean [SD], 55.2 [6.5] and 55.8 [5.5], respectively). Beginning at Week 4, mean HIVTSQs scores in the DTG/3TC group further increased vs. CAR and were sustained through Week 48. Baseline mean (SD) HIV-SDM symptom bother scores were comparable between the DTG/3TC (9.0 [9.9]) and CAR (7.9 [9.3]) groups. Small improvements in HIV-SDM scores favoring DTG/3TC were observed at Weeks 4 and 24 and sustained through Week 48 (though not significant between groups). Participants aged ≥ 50 and < 50 years who switched to DTG/3TC reported higher satisfaction and less symptom distress vs. CAR; these results were generally comparable between age groups. Participants who switched to DTG/3TC reported rapid and sustained improvements in treatment satisfaction compared with those who continued CAR, reinforcing the benefits of DTG/3TC beyond virologic suppression (NCT04021290; registration date, 7/11/2019)., Competing Interests: Declarations. Ethical Approval: This study was designed in agreement with the International Conference on Harmonization Good Clinical Practice and adhered to the principles of the Declaration of Helsinki. Study documents were reviewed and approved by national, regional, or investigational center ethics committees or institutional review boards. Consent to Participate: Written informed consent was obtained before participant screening. Consent to Publish: Not applicable. Competing Interests: PK has received grants from Gilead, Merck, Theratechnologies, and ViiV Healthcare/GSK (paid to institution); has received consulting fees from and participated in data safety monitoring/advisory boards for Gilead, Merck, and ViiV Healthcare/GSK; and holds stock/stock options in Gilead, GSK, Johnson & Johnson, Merck, Moderna, and Pfizer. AEC has received grants from Gilead, GSK, MSD, and ViiV Healthcare (paid to institution); speaker fees from MSD; travel/meeting support from Gilead and ViiV Healthcare; and has participated in advisory boards for MSD, Theratechnologies, and ViiV Healthcare. CJ-O has received consulting fees from GSK and ViiV Healthcare; honoraria from AbbVie, CCO, Gilead, GSK, Janssen-Cilag, and ViiV Healthcare; payment for expert testimony from GSK and ViiV Healthcare; travel/meeting support from CCO, Gilead, GSK, Janssen-Cilag, MSD, and ViiV Healthcare; has participated in data safety monitoring/advisory boards for Gilead, GSK, Janssen-Cilag, MSD, and ViiV Healthcare; and holds a leadership role with BAGNAE. MGD has received grants and honoraria from and participated in data safety monitoring/advisory boards for AbbVie, Gilead, Janssen, MSD, and ViiV Healthcare; has received meeting/travel support from Gilead and Janssen; and has received equipment/materials from Gilead. SDG has no competing interests. CB has received research grants from GSK and Pfizer and received speaker fees from and participated in advisory boards for Gilead, GSK, and Merck. LH has received honoraria and meeting/travel support from Gilead, MSD, and ViiV Healthcare. P-LL has no competing interests. JO, AO, BW, BJ, LAE, DF, MK, and JP are employees of GSK or ViiV Healthcare and may own stock in GSK., (© 2024. The Author(s).)

HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4 + T cells obtained after antiretroviral treatment interruption, while CD4 + T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The Central African Republic (CAR) is characterized by widespread HIV epidemic with notable prevalence and genetic diversity. We herein analysed the genetic diversity of atypical non-M HIV-1 strains. In-house serotyping assays for variants of HIV-1 (M, N, O, P) and HIV-2 were used to test a biological collection of 6092 HIV-seropositive blood samples collected between 2003 and 2014 at the Institut Pasteur de Bangui. Samples indicative of recombinant M/O groups, HIV-2, or those that yield doubtful/negative results underwent further PCR tests and sequencing. We found six atypical HIV strains: specifically, three (0.05%) HIV-1 group O strains (subtype H) detected in samples from 2005, 2008 and 2009, alongside three (0.05%) HIV-2 strains (two group A and one group B) identified in samples from 2007 and 2009. HIV-1/O strains showed a genetic link to Cameroon and Gabon strains. This study highlights the dominance of HIV-1/M in the CAR's HIV epidemic over time and underscores the infrequent occurrence of HIV-1 group O and HIV-2 strains. These findings validate the efficacy of WHO-recommended HIV testing protocols and emphasize the need for adaptive surveillance and management strategies to confront the complexities introduced by the genetic diversity of HIV strains., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Purpose: The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT., Methods and Materials: Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients., Results: The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women., Conclusions: HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An oral two-drug regimen (O2DR) in the form of a once-a-day single tablet is now recommended for treatment switching and treatment initiation for HIV. In clinical care, the process of treatment change refers to adaptation issues, both individual and within the care relationship. The study aim is to present the determinants involved in the acceptability of switching to O2DR in the PROBI (Patient-Reported Outcomes BItherapy) qualitative study. The study includes 30 interviews: 15 were conducted with doctors caring for people living with HIV, 15 were conducted with patients who had been offered a change of treatment. A double analysis was carried out: lexicometric analysis to highlight the structuring of the discourse around the change in treatment and a thematic analysis to understand the associated issues more precisely. The results highlighted common concerns with respect to switching to O2DR. Also, the caregiver-patient relationship was a central determinant in treatment switching. Information, knowledge and representations of O2DR are also factors facilitating treatment change and should be taken into account for doctors' and patients' adherence., Competing Interests: I have read the journal’s Policy and the authors of this manuscript have the following competing interests: CD has received consultancies, speaker honoraria and travel grants from Gilead, Janssen-Cilag, MSD and Viiv Healthcare; GM has received fees for participation in advisory boards or presentations from Gilead and MSD; CA has received travel grants and honoraria from Gilead, Viiv Healthcare and MSD; LH has received fees for participation in advisory boards or présentations from Viiv Healthcare and Merck, LH has received travel support for congress attendance from Viiv Healthcare, Merck, Gilead and Shape and Dohme; MD has received consultancies, speaker honoraria and travel grants from Gilead, MSD and Viiv Healthcare; OC has received consultancies and speaker honoraria from Gilead and Viiv Healthcare. The following authors have declared that no competing interests exist: ASP, OT, GR and DZ., (Copyright: © 2024 Petit 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.)

Despite the substantial national resources invested in the fight against HIV to achieve its elimination, its incidence has remained stable in recent years. In 2022, the FOPH estimated that 7% of people living with HIV in Switzerland remained undiagnosed, underlining the potential for improving screening. The aim of this article is to present the process of HIV screening and diagnosis in clinical practice, adapted to the Federal Office of Public Health (FOPH) national strategy, and including the different indications for screening, the interpretation of available tests, and the place of post-exposure prophylaxis (PEP)., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Immune checkpoint inhibitors (ICIs) have been a major advance in cancer management. However, we still lack prospective real-world data regarding their usage in people with HIV infection (PWH)., Methods: The ANRS CO24 OncoVIHAC study (NCT03354936) is an ongoing prospective observational cohort study in France of PWH with cancer treated with ICI. We assessed the incidence of grade ≥3 immune-related adverse events (irAEs). All grade ≥3 irAEs were reviewed by an event review., Results: Between January 17, 2018, and December 05, 2023, 150 participants were recruited from 33 sites and 140 were included in this analysis. At the data cut-off date of December 05, 2023, the median follow-up was 9.2 months (IQR: 3.9-18.3), with a total of 126.2 person-years.Median age was 59 years (IQR: 54-64) and 111 (79.3%) were men. Median time since HIV diagnosis was 25 years (12-31), the median duration on antiretroviral (ARV) was 19.5 years (7.7-25.4), and the CD4 nadir was 117/µL (51-240). ICI regimens comprised anti-programmed cell death protein-1 (PD-1) for 111 (79.3%) participants, anti-programmed death-ligand 1 for 25 (17.9%), a combination of anti-PD-1 and anti-cytotoxic T-lymphocyte associated protein 4 for 3 (2.1%), and anti-PD-1 along with anti-vascular endothelial growth factor receptor for 1 (0.7%). The most frequent cancers were lung (n=65), head/neck (n=15), melanoma (n=12), liver (n=11) and Hodgkin's lymphoma (n=9).During follow-up, a total of 34 grade ≥3 irAEs occurred in 20 participants, leading to an incidence rate of 26.9 per 100 person-years. The Kaplan-Meier estimates of the proportion of participants with at least one episode of grade ≥3 irAEs were 13.8% at 6 months, 15.0% at 12 months and 18.7% at 18 months. One treatment-related death due to myocarditis was reported (0.7%). Multivariable analysis of cumulative incidence showed that participants with time since HIV diagnosis >17 years (incidence rate ratio (IRR)=4.66, p=0.002), with CD4<200 cells/µL (IRR=4.39, p<0.0001), with positive cytomegalovirus (CMV) serology (IRR=2.76, p=0.034), with history of cancer surgery (IRR=3.44, p=0.001) had a higher risk of incidence of grade ≥3 irAEs., Conclusion: This study showed that the incidence of a first episode of grade ≥3 irAE was 15.0% (95% CI: 9.6% to 22.9%) at 1 year and the cumulative incidence of all severe irAE episodes was 26.9 per 100 person-years. Low CD4 count, positive CMV serology, history of cancer surgery and a longer time since HIV diagnosis were associated with the occurrence of severe irAEs., Competing Interests: Competing interests: DC received personal fees from Pfizer for a lecture outside of the submitted work. A-GM and CK received consulting fees from Gilead Sciences, Merck, and ViiV. J-PS received grant from MSD avenir and personal fees from Roche, MSD, AZ, Novartis, leopharma, PFO, Lilly, Gilead, Daichy-sakyo, and Pfizer for lectures, presentations, speakers bureaus, manuscript writing or educational events outside of the submitted work. OL reports paid expert testimony and consultancy fees from BMS France, MSD; consultancy fees from Boehringer, AbbVie. BA reports research grant from MSD avenir, and consulting fees or honoraria from Novartis, AstraZeneca, BMS, MSD, Astellas, and Sanofi. MV received consulting fees from Gilead Sciences. All other authors declare no competing interests., (© 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: Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. In this study, we report month 12 clinical outcomes in patient study participants (PSPs) in the CAB and RPV Implementation Study in European Locations (CARISEL) study., Setting: CARISEL is a phase 3b implementation-effectiveness study., Methods: CARISEL was designed as a 2-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, this study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through month 12 included the proportion of PSPs with plasma HIV-1 RNA ≥50 and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability., Results: Four hundred thirty PSPs were enrolled and treated; the mean age was 44 years (30% ≥50 years), 25% were women (sex at birth), and 22% were persons of color. At month 12, 87% (n = 373/430) of PSPs maintained HIV-1 RNA <50 copies/mL, with 0.7% (n = 3/430) having HIV-1 RNA ≥50 copies/mL. One PSP had CVF. The safety profile was consistent with previous findings. Overall, the results were similar between implementation arms., Conclusion: CAB + RPV LA Q2M was well tolerated and highly effective in maintaining virologic suppression with a low rate of virologic failure., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity., Competing Interests: Potential conflicts of interest. O. Z. F. received honoraria from Gilead for a presentation after the 2023 Conference on Retroviruses and Opportunistic Infections, as well as support from ViiV Healthcare for traveling to and attending the European AIDS Conference in October 2023 and the Société Française de Lutte contre le Sida conference in 2022. T. M. D. received grants/contracts from the U.S. National Cancer Institute for the ANCHOR study, central pathology review, and salary support to the University of California, San Francisco. C. J. A.'s employer received an unrestricted research grant from GSK for an investigator-initiated research project not related to this work. I. E. has received payment or honoraria from Merck Sharp & Dohme for an educational event for practitioners. 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.)

Introduction: Cabotegravir plus rilpivirine (CAB + RPV) is the first complete long-acting (LA) regimen recommended for maintaining HIV-1 virological suppression. Cabotegravir And Rilpivirine Implementation Study in European Locations (CARISEL) is an implementation-effectiveness study examining the implementation of CAB+RPV LA administered every 2 months (Q2M) in European HIV centres. We present staff study participant (SSP) perspectives on the administration of CAB+RPV LA over 12 months., Methods: Eighteen clinics were randomized to one of two implementation support packages: standard arm (Arm-S) or enhanced arm (Arm-E). Arm-S included video injection training and provider/patient toolkits. Additionally, Arm-E included skilled wrap-around team meetings, face-to-face injection training and continuous quality improvement (CQI) calls. SSPs completed surveys on the acceptability, appropriateness and feasibility of CAB+RPV LA as an intervention and its implementation into their clinics, as well as barriers and facilitators to implementation. All surveys were completed at Month (M)1 (baseline), M5 and M12; data collection was completed by February 2022. Qualitative data were obtained from semi-structured interviews at M1, M5 and M12. The primary objective was assessed via formal statistical comparisons between study arms of the Acceptability of Implementation Measure, Implementation Appropriateness Measure and Feasibility of Implementation Measure surveys (1-5 Likert scale ranging from 1 = "completely disagree" to 5 = "completely agree"). Equivalent measures anchored to CAB+RPV LA as a therapy were also assessed., Results: Seventy SSPs completed surveys and interviews at M1, 68 at M5 and 62 at M12. Mean acceptability/appropriateness/feasibility scores were ≥3.8 (out of 5) at M12 for implementation- and intervention-based measures. An analysis of covariance showed no significant differences between study arms for these outcomes. Although barriers were noted, most SSPs were not overly concerned that these would impact implementation; concern about these anticipated barriers also decreased over time. At M12, 90.3% (n = 56/62) of SSPs held a positive opinion about CAB+RPV LA implementation. Qualitative interviews and CQI calls highlighted three top practices that supported implementation: implementation planning; education about CAB+RPV LA clinical efficacy; and education around administering injections and managing pain/discomfort after injections., Conclusions: CARISEL demonstrated that CAB+RPV LA dosed Q2M was successfully implemented across a range of European locations, with SSPs finding implementation highly acceptable, appropriate and feasible., Gov Number: NCT04399551., (© 2024 ViiV Healthcare and The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods. In contrast to other approaches, which use one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for the accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained and sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of distinct HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using an in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires., (© 2024. The Author(s).)

Background: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences., Materials and Methods: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales., Results: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48., Conclusions: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment., Trial Registration: ClinicalTrials.gov NCT03160105.

Background: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear., Methods: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality., Results: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies., Conclusions: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM., Competing Interests: Potential conflicts of interest. A. Ma. is full-time employee at Gilead Sciences and owns stock. A. Mo. has received travel support, lecture and consultancy fees from Gilead, ViiV Healthcare, and Eiland and Bonnin, all outside the submitted work. A. E. has received consulting fees and honoraria for lectures and presentations from Roche. C. M. has received honoraria for lectures and presentations from Gilead, ViiV Healthcare, MSD, and travel support from Gilead and a research grant to institution from Gilead. J. J. V. has received honoraria for lectures and presentations from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, Deutsches Zentrum für Infektionsforschung, Uniklinik Freiburg/Kongress und Kommunikation, Akademie für Infektionsmedizin, University Manchester, Deutsche Gesellschaft für lnfektiologie, Ärztekammer Nordrhein, Uniklinik Aachen, Back Bay Strategies, Deutsche Gesellschaft für Innere Medizin, Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, and is part of the data safety monitoring board of APOGEPHA Arznemittel, Biontech, Merck/MSD, Gilead, and Pfizer; and reports research funding from Merck/MSD; Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zetrum für Luft und Raumfahrt (DLR), University of Bristol, Rigshospitalet Kopenhagen. A. C. has received honoraria for lectures and presentation and meetings attendance support from Gilead, ViiV Healthcare, MSD, Janssen-Cilag and is part of the advisory board of Gilead, ViiV Healthcare, MSD and Janssen-Cilag. J. B. has received consulting fees and honoraria for lectures and presentations from ViiV Healthcare, Merck, Gilead, Janssen, Pfizer, and Theratechnology, and honoraria from NovoNordisk and AtraZeneca. S. W. is part of the advisory board of ViiV Healthcare and reports grants or contracts paid to institution from RESPOND. R.M. has received consultancy fees from Tamro Baltics, honoraria honoraria for lectures and presentations from MSD, KRKA, Tamro Baltics, AbbVie and Eurovaistine, payment for expert testimony from Tamor Baltic and meeting attendance support from AbbVie, MSD, Johnson&Johnson, and Swixx BioPharma; and reports unpaid roles as Board member of Lithuanian Infectious Diseases Society and as Scientific committee member of EuroSIDA; and the following grants or contracts unrelated to this work: EuroSIDA/Respond, observational cohort study; WEEPI 1.1, WEEPI 1.2 (Western-Eastern European partnership Initiative on HIV, viral hepatitis and TB). J. T. is a member of the European AIDS Treatment Group, a community organization that receives funding not related to this publication from ViiV Healthcare, Gilead Sciences, MSD, Janssen, Orasure Technologies, European Union (author was paid for project work), Innovative Medicines Initiative, FIND Diagnosis, received consulting fees/honoraria from The Global Fund, UNAIDS, Pan American Health Organization, Frontline AIDS, the Barcelona Institute for Global Health. H. G. is an employee of ViiV healthcare and shareholder of GSK. A.Ma. is an employee and shareholder of Gilead Sciences California. H. C. B. has received in the 36 months prior to the submission of this manuscript one grant from Gilead that was not related to this project. HCB has served as the president of the “association contre le HIV et autres infections transmissibles.” In this role he has received support for the Swiss HIV Cohort Study from ViiV Healthcare, Gilead, BMS, and MSD. M. L. reports paid participation on DSMB with Certa Therapeutics. F.W. reports participation in advisory board for ViiV Healthcare. 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.)

ABSTRACT In resource-limited settings, alternatives to HIV viral load testing may be necessary to monitor the health of people living with HIV. We assessed the utility of self-report antiretroviral therapy (ART) to screen for HIV viral load among persons who inject drugs in Hai Phong Vietnam, and consider differences by recent methamphetamine use. From 2016 to 2018 we recruited PWID through cross sectional surveys and collected self-report ART adherence and HIV viral load to estimate sensitivity, specificity, positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-) for self-reported ART adherence as a screening test for HIV viral load. We used three HIV viral load thresholds: < 1000, 500 and 250 copies/mL; laboratory-confirmed HIV viral load was the gold standard. Among 792 PWID recruited, PPV remained above 90% regardless of recent methamphetamine use with slightly higher PPV among those not reporting recent methamphetamine use. The results remained consistent across all three HIV viral load thresholds. Our findings suggest that when HIV viral load testing is not possible, self-reported ART adherence may inform decisions about how to prioritize HIV viral load testing among PWID. The high PPV values suggest self-reported high ART adherence indicates likely HIV viral suppression, irrespective of methamphetamine use.

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p  = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Introduction: We assessed the impact of a nationwide screening programme to reduce the risk of anal cancer in a large cohort of high-risk patients with HIV., Methods: From a large database from one referral centre, all high-risk patients with HIV (men who have sex with men, history of anal or genital warts, or previous cervix human papillomavirus-related lesions) who were eligible to enter the French anal cancer screening programme (2011-2020) were retrospectively included. Adherence to the screening programme was defined as no interval >18 months between two visits. Standardized management included perianal visualization and standard anoscopy with biopsies of macroscopic abnormalities., Results: Overall, 700 patients with HIV were included (median follow-up 8.4 years [interquartile range 4.3-9.2] and 1491.6 patient-years), and 336 had one or more proctology visit. A total of 13 patients were diagnosed with anal squamous cell carcinomas. The risk of anal cancer was higher with anal intra-epithelial neoplasia grade 3 (AIN3; hazard ratio [HR] 44.5 [95% confidence interval {CI} 11.2-176.6], p < 0.001), AIN2 (HR 11.9 [95% CI 2.1-66.9], p = 0.005), or high-grade dysplasia (HR 23.4 [95% CI 7.9-69.1], p < 0.001) than with low-grade dysplasia or no lesion. Among the patients who were strictly adherent to the screening programme (4.6% [32/700]), we did not report any AIN or anal cancer, but we also did not observe any significant reduction in the risk of anal cancer (p = 0.51), AIN3 (p = 0.28), high-grade dysplasia (p = 0.19), or any AIN lesions (p = 0.10) compared with non-adherent patients. In contrast, screened patients were more likely to be diagnosed with anal warts (HR 3.71 [95% CI 2.14-6.42], p < 0.001)., Conclusion: Macroscopic high-grade dysplasia lesions are associated with a higher risk of developing anal cancer. Despite finding no cases of cancer during the screening programme, we also did not demonstrate a clear benefit from our screening programme for the prevention of anal cancer in high-risk patients with HIV., (© 2023 British HIV Association.)

Objectives: As many disparities in the clinical use of HIV DNA sequencing are observed, a DELPHI-type consensus was initiated in France to homogenize use, techniques and interpretation of results., Methods: Based on a literature review and clinical experience, a steering committee (SC) of eight virologists and one infectious disease specialist formulated statements. Statements were submitted to an independent and anonymous electronic vote of virologists and HIV clinicians in France, between October 2022 and December 2022., Results: The SC developed 20 statements grouped into six categories: clinical situations for the use of HIV DNA genotyping; techniques for performing HIV DNA genotyping; consideration of apolipoprotein B mRNA editing enzyme (APOBEC) mutations; genotyping results reporting; recycling of antiretrovirals; and availability of HIV DNA genotyping tests and delays. Twenty-one virologists and 47 clinicians participated in two voting rounds and 18/20 (90%) assertions reached a 'strong' consensus. For example, that prior genotyping on HIV DNA is useful for clinical decision-making when considering switching to some long-acting regimens or to reduce the number of antiretroviral agents in virologically suppressed patients for whom RNA data are unavailable/not exploitable/not sufficiently informative. Two statements achieved no consensus: reporting any detected viral minority population for discussion in multidisciplinary meetings (virologists), and possible risk of virological failure when using a second-generation InSTI plus lamivudine or emtricitabine regimen in patients with undetectable viral load within ≥1 year and in the presence of a documented M184V mutation within the last 5 years (clinicians)., Conclusions: This DELPHI-type consensus will facilitate the strengthening and harmonization of good practice when performing HIV DNA sequencing., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: The persistence of intact replication-competent HIV-1 proviruses is responsible for the virological rebound off treatment. The gut could be a major reservoir of HIV-1 due to the high number of infected target cells., Methods: We collected blood samples and intestinal biopsies (duodenum, ileum, colon) from 42 people with HIV-1 receiving effective antiretroviral therapy. We used the Intact Proviral DNA Assay to estimate the frequency of intact HIV-1 proviruses in the blood and in the intestinal mucosa of these individuals. We analyzed the genetic complexity of the HIV-1 reservoir by performing single-molecule next-generation sequencing of HIV-1 env DNA. The activation/exhaustion profile of mucosal T lymphocytes was assessed by flow cytometry., Findings: Intact proviruses are particularly enriched in the colon. Residual HIV-1 transcription in the gut is associated with persistent mucosal and systemic immune activation. The HIV-1 intestinal reservoir appears to be shaped by the proliferation of provirus-hosting cells. The genetic complexity of the viral reservoir in the colon is positively associated with TIGIT expression but negatively with PD-1, and inversely related to its intact content. The size of the intact reservoir in the colon is associated with PD-1 + TIGIT - mucosal CD4 + T cells, particularly in CD27 + memory cells, whose proliferation and survival could contribute to the enrichment of the viral reservoir by intact proviruses., Interpretation: Enrichment in intact proviruses makes the gut a key compartment for HIV-1 persistence on antiretroviral therapy., Funding: This project was supported by grants from the ANRS-MIE (ANRS EP61 GALT), Sidaction, and the Institut Universitaire de France., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Human Papillomavirus (HPV)-35 accounts for up 10% of cervical cancers in Sub-Saharan Africa. We herein assessed the genetic diversity of HPV35 in HIV-negative women from Chad (identified as #CHAD) and HIV-infected men having sex with men (MSM) in the Central African Republic (CAR), identified as #CAR. Ten HPV35 DNA from self-collected genital secretions (n = 5) and anal margin samples (n = 5) obtained from women and MSM, respectively, were sequenced using the ABI PRISM® BigDye Sequencing technology. All but one HPV35 strains belonged to the A2 sublineage, and only #CAR5 belonged to A1. HPV35 from #CAR had higher L1 variability compared to #CHAD (mean number of mutations: 16 versus 6). L1 of #CAR5 showed a significant variability (2.29%), suggesting a possible intra-type divergence from HPV35H. Three (BC, DE, and EF) out of the 5 capsid loops domains remained totally conserved, while FG- and HI- loops of #CAR exhibited amino acid variations. #CAR5 also showed the highest LCR variability with a 16bp insertion at binding sites of the YY1. HPV35 from #CHAD exhibited the highest variability in E2 gene (P<0.05). E6 and E7 oncoproteins remained well conserved. There is a relative maintenance of a well conserved HPV35 A2 sublineage within heterosexual women in Chad and MSM with HIV in the Central African Republic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mboumba Bouassa 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: Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals., Methods: Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, the model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and nonobese individuals., Results: The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with nonobese (BMI: 18.5-25 kg/m2) individuals, consistent with observed clinical data. Etravirine and rilpivirine were the most impacted, especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load than nonobese PWH., Conclusions: The concentrations of ARVs are modestly reduced in obese individuals, with no negative impact on the virological response. Our data provide reassurance that standard doses of ARVs are suitable in obese PWH, including those who gained substantial weight with some of the first-line ARVs., Competing Interests: Potential conflicts of interest. F. S. reports grants or contracts and stock or stock options from Certara UK Ltd, Simcyp Division (employee). P. E. T. received grants and educational and advisory fees to their institution from Gilead, MSD, and ViiV, outside the submitted work. The institution of M. C. has received research grants from Gilead, MSD, and ViiV. D. L. B. reports honoraria paid to him for advisory boards and lectures from Gilead, Merck, and ViiV, outside the submitted work. The institution of A. H. has received travel grants and congress and advisory fees from MSD, ViiV, and Gilead unrelated to this work. E. B. received consultant fees and travel grants to their institution from Gilead, MSD, ViiV, Pfizer, AbbVie, Ely Lilly, and Moderna, outside the submitted work. A. C. reports unrestricted educational grants from MSD, Gilead, and ViiV. C. M. has received speaker honoraria from MSD, ViiV, Gilead, and Pfizer unrelated to this work. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE form for disclosure of potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Depression is highly prevalent in people living with HIV (PLWH) but remains under treated in Sub-Saharan Africa. In this context, we conducted the first study of Group Interpersonal Therapy (IPT) to treat depression in PLWH in Senegal. We assessed the perceptions and experiences of patients and group facilitators, as well as barriers to implementation., Methods: This study was conducted at the Fann National University Hospital Center in Dakar, the urban capital of Senegal. Qualitative data were collected during the implementation phase (February to June 2020 and then from January to February 2021), with a 6-month pause due to the COVID-19 pandemic. Twenty-five patients and three group facilitators were individually interviewed by a socio-anthropologist. Qualitative data were analyzed thematically., Results: Group IPT was perceived as successful and beneficial by patients and facilitators. Patients reported positive experiences with group IPT and sustained outcomes. Beyond improving depressive symptoms, patients reported improvements in their social and professional lives, and the development of skills to prevent relapse. Group facilitators noted the benefits of therapy for their patients and for their professional skills, reporting greater clinical competence and improved supportive skills. Challenges to intervention implementation included confidentiality and patient privacy concerns, healthcare accessibility issues, and time demands., Conclusion: In this first qualitative study of group IPT for depression in PLWH in Senegal, participants described both positive experiences with the intervention and challenges to its implementation. Future studies, conducted in suburban and rural communities outside of Dakar, would further inform the implementation of IPT in Senegal., 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 © 2024 Bernard, Mané, Ziadeh, Tine, Diaw, Benzekri, Ndiaye, Samba, Font, Bottai, Jacquesy, Verdeli, Ngom, Dabis, Seydi and de Rekeneire.)

Objectives: Describe the dental care pathway of people living with HIV (PLHIV) and their oral pathologies., Materials and Methods: A monocentric cross-sectional study involving adult PLHIVs followed (October 2021/April 2022) in our department. Socio-demographic and medical data, course of dental care, and presence of pathologies of the oral mucosa were recorded., Results: 112 PLHIV (71% men, 54 ± 14 years) were included. Of the 112, 96% had already consulted a dentist, and 78% had a referring dentist; 73% had disclosed their seropositivity; for 84%, the visit proceeded normally, 7% refused treatment; for 8%, the dentist was not comfortable, and for 4% the dentist's attitude became negative; 21% of the PLHIV had already encountered difficulties in finding a dentist including 37% because of their viral status. Among the oral pathologies listed, 23 lesions were identified: 15 (65%) were unrelated to HIV, 4 (17%) were classified stages B/C (1 Kaposi's sarcoma, 1 oral villous leukoplakia, 2 chronic candidiasis), and 4 (17%) were lesions with evolution specifically due to HIV (2 inhomogeneous leukoplakias, 1 cancer, 1 verrucous papilloma)., Conclusion: Although 78% of the PLHIV included had a referring dentist, discrimination by dentists toward PLHIV still persists (16% of the PLHIV concerned)., Clinical Relevance: 27% of participants did not feel ready to disclose their infection. The resulting lack of follow-up is also a loss of opportunity because while most of the small number of oral lesions diagnosed in this population are related to age or comorbidities, some are serious and need to be identified., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The impact of the coronavirus disease 2019 (COVID-19) pandemic on the clinical follow-up of people living with HIV (PLWH) remains poorly documented in Sahelian Africa. We conducted a monocentric retrospective investigation of the outcomes (loss to follow-up [LTFU], transferred, or dead) among a cohort of PLWH receiving antiretroviral treatment (ART) in N'djamena, Chad (December 2019-December 2022). The incidence of LTFU was found to be higher in 2020 than in 2022 (P > 10-4), with increases of incidence of LTFU in the first trimester of 2020 before identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cases in Chad. The all-cause mortality was low and did not appear to be influenced by SARS-CoV-2 infection waves. Our data reveal a concerning trend of significantly increased LTFU among PLWH receiving ART during the COVID-19 pandemic. Our findings indicate that it is crucial to provide accurate information to ensure the continuity of care for PLWH during a sanitary crisis in Sahelian Africa.

Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with < 10 pack-years exposure were of similar magnitude to those from controls. Regarding PWV, HOMA-R and eGFR, no significant differences were found, with the exception of eGFR values which were globally lower in HIV-1 infected patients. In conclusion HIV infection and smoking acted synergistically and were associated with a wasting phenotype combining muscle mass and bone mineral reduction.Clinical Trial Registration (registrar, website, and registration number), where applicable: CPP 10-023, 09-027, 10-034., (© 2023. The Author(s).)

Background: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events., Methods: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates., Findings: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52)., Interpretation: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV., Funding: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism., Competing Interests: Declaration of interests SMR, RWL, and SMI report National Institutes of Health (NIH) grants paid to their institution during the conduct of the study. SL reports grants from the NIH and the Providence/Boston Center for AIDS Research. MAH reports grants from the NIH and personal honoraria from Cytel, ProPublica, and ADIA Lab. JACS reports grants from the NIH and UK National Institute for Health and Care Research (NIHR). AP received grants from the Wellcome Trust, the Bill & Melinda Gates Foundation, the NIH, and UK NIHR and payments from the Gates Foundation outside of the study. FB reports grants and personal fees from Gilead Sciences, outside the submitted work. IJ reports payments from Gilead Sciences, GESIDA, and ViiV Healthcare. MJG participated on advisory boards for Merck, Gilead, and ViiV. MBK has received grants and honoraria from ViiV Healthcare, AbbVie, and Gilead. LM reports grants from ANRS-MIE INSERM paid to her institution. RL received grants from Canadian Institutes of Health Research, Alberta Innovates, and the University of Calgary outside of the study. PR reports grants from Gilead Sciences, ViiV Healthcare, and Merck & Co. CAS and MvdV report grants and honoraria from Gilead Sciences, ViiV Healthcare, and MSD outside of the submitted work. BS reports financial support to his institution for travel grants from Gilead Sciences and ViiV healthcare, and for advisory boards from Gilead Sciences. GT received grants from Gilead Sciences and University College London and EU and national funds. AvS reports grants from the Dutch Ministry of Health, Welfare, and Sport and the European Centre for Disease Prevention and Control. LW received grants from ANRS-MIE. JMM has received consulting honoraria and research grants from Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work. JMM has also received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain, during 2017–24. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

HIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1-infected humans. We show that only class-switched memory B cells markedly differ between subjects treated during the acute and chronic phases of infection. Intestinal memory B-cell monoclonal antibodies show more prevalent polyreactive and commensal bacteria-reactive clones in late- compared to early-treated individuals. Mirroring this, serum IgA polyreactivity and commensal-reactivity are strongly increased in late-treated individuals and correlate with intestinal permeability and systemic inflammatory markers. Polyreactive blood IgA memory B cells, many of which egressed from the gut, are also substantially enriched in late-treated individuals. Our data establish gut and systemic B-cell polyreactivity to commensal bacteria as hallmarks of chronic HIV-1 infection and suggest that initiating treatment early may limit intestinal B-cell abnormalities compromising HIV-1 humoral response., (© 2023. Springer Nature Limited.)

Introduction: Cervical cancer related to high risk-human papillomavirus (HR-HPV) is the second female cancer in the Republic of Congo (Congo). We herein evaluated the molecular epidemiology of cervical HPV infection and associated risk factors in Congolese women living in urban (Brazzaville) and rural (Plateaux department) settings., Patients and Methods: A population-based, cross-sectional survey was conducted to collect demographic and behavioral data among Congolese women, and to obtain endocervical swab samples for HPV DNA molecular detection (Anyplex II HPV28, Seegene, Seoul, South Korea)., Results: A total of 284 women (mean age: 37.8 years; HIV-1-positivity: 18.6%) were included. The prevalence of HPV DNA cervical shedding was 64.4% [HR-HPV: 80.9%, mainly HPV-16 (15.8%), and HPV-35 and HPV-52 (15.3%); multiple HPV infections: 60.6%; 9-valent HPV Gardasil-9® vaccine genotypes: 42.6%]. 91.6% and 100% of low-grade squamous intraepithelial neoplasia (LSIL) and cervical cancer, respectively, showed HR-HPV. HR-HPV prevalence was higher among students (aOR: 7.9) and HIV-infected women (aOR: 3.1) in Brazzaville, and among women aged between 21-30 years (aOR: 7.2) and HIV-infected women (aOR: 5.1) in the Plateaux department., Conclusion: Cervical HR-HPV infection is particularly frequent in young or HIV-infected Congolese women. Prophylactic HPV vaccination combined with primary molecular screening of HR-HPV infection in this country should be extended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: We aimed to examine the association of the country of birth and the other patients' characteristics with the prescription of two-drug regimens (2DRs) in virally suppressed people with HIV (PWH) in France., Design: Observational study conducted from the national Dat'AIDS prospectively collected database., Methods: We included all adults who were actively in care on 31 December 2020 in 26 French centers, with an HIV plasma viral load (pVL) <50 copies/ml for at least 6 months while on antiretroviral therapy (ART). Patients with chronic hepatitis B were excluded because they are not eligible to 2DRs. Univariate and multivariate logistic regressions were built to analyze relationships between patients' characteristics and receiving a 2DR., Results: We analyzed data from 28 395 PWH: 41.7% men who have sex with men, 31.7% women and 26.5% heterosexual men; 35% born abroad. Median age was 53 years [interquartile range (IQR) 44-60]; ART duration 14 years (8-23); duration of virological suppression 87 months (42-142). 2DRs (mainly dolutegravir/rilpivirine, 53.8%, or dolutegravir/lamivudine, 41.7%) were prescribed in 16.3% of the patients and were less common in the 'born abroad' group (18.9% versus 11.5%). The multivariate model showed that individuals born in France were more likely to receive a 2DR [adjusted odds ratio (aOR): 1.62 [1.50-1.74]], independently of other characteristics. Older PLWH and those with higher CD4 + T-cell counts were also more likely to receive a 2DR., Conclusion: Despite unrestricted access to ART in France, independently from HIV disease parameters, PWH born abroad were less likely to receive 2DRs as a maintenance regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the 324 GDIR 327 V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Concerns have been raised regarding neuropsychiatric adverse drug reactions of integrase inhibitors (INSTIs) in patients living with HIV. The aim of this study was to assess the risk of depression and suicidality reporting with INSTIs based on a global pharmacovigilance database., Methods: Depression and suicidality cases in patients treated with INSTIs were identified within the WHO global database of individual case safety reports, VigiBase. Risk of depression and suicidality reporting with INSTIs compared with other ART was assessed using disproportionality analyses (case/non-case statistical approach)., Results: Of 19 991 410 reports over the study period, 124 184 reports concerned patients exposed to ART, including 22 661 patients exposed to an INSTI. Among patients treated with an INSTI, 547 cases of depression and 357 cases of suicidality were identified. Disproportionality analyses showed that depression [reporting OR (ROR) 3.6; 95% CI: 3.2-4.0] and suicidality (ROR 4.7; 95% CI: 4.1-5.4) were more reported with the use of INSTIs compared with other ART. Amongst INSTIs, depression reporting was significantly greater for bictegravir and dolutegravir, whereas suicidality reporting was significantly greater for dolutegravir only., Conclusions: Our findings suggest that depression and suicidality are adverse drug reactions of all INSTI agents, especially dolutegravir, which may occur within the first months of therapy., (© 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.)

Objectives: To minimize confounding factors, we aimed to describe the changes in weight and body mass index (BMI) following the single substitution of tenofovir disoproxil fumarate (TDF) by tenofovir alafenamide (TAF) in people living with HIV (PLWH)., Methods: We designed a retrospective study in a large French cohort. We included all HIV-suppressed adults under TDF + emtricitabine + rilpivirine or elvitegravir/cobistat, who experienced a first switch from TDF to TAF, while other antiretrovirals remained unchanged (Switch group). We compared this population to a propensity score-matched Control group (1:1) who stayed on the same TDF-based regimen. Changes were evaluated after 6 (M6) and 12 months (M12)., Results: Some 1260 and 468 PLWH were evaluable per group at M6 and M12, respectively. In the Switch group, there was a mean (95% confidence interval [95% CI]) weight gain of +1014 g (+826 to +1201) at M6 (p < 0.0001) and +1365 g (+910 to +1820) at M12 (p < 0.0001), as compared with baseline. Meanwhile, there was no significant weight gain at M6 (+139 g [-50 to +328]) and M12 (-32 g [-413 to +350]) in the matched Control group. Similarly, mean BMI increased significantly in the Switch group at M6 (+0.35, 95% CI: +0.29 to +0.41, p < 0.0001) and M12 (+0.49, 95% CI: +0.32 to +0.65, p < 0.0001), while it was stable at M6 (+0.05, 95% CI: -0.01 to +0.12, p = 0.11) and M12 (+0.01, 95% CI: -0.12 to +0.14, p = 0.89) in the No Switch group., Conclusions: Although modest, there is a significant weight gain following the substitution of TDF by TAF. This should be anticipated in certain at-risk populations., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objectives: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation., Design: Observational study conducted from the national Dat'AIDS prospectively collected database., Methods: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400 copies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan-Meier model., Results: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33-1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth., Conclusion: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Because NRTIs can have fetal toxicities, we evaluated a perinatal NRTI-sparing strategy to prevent perinatal HIV transmission. Our primary objective was to determine the proportion maintaining a viral load (VL) of <50 copies/mL up to delivery on darunavir/ritonavir monotherapy, without requiring treatment intensification., Methods: In a one-arm, multicentre Phase 2 clinical trial, eligible patients in the first trimester of pregnancy on ART with plasma VL < 50 copies/mL received maintenance monotherapy with darunavir/ritonavir, 600/100 mg twice daily. VL was monitored monthly. ART was intensified in the case of VL > 50 copies/mL. Neonates received nevirapine prophylaxis for 14 days., Results: Of 89 patients switching to darunavir/ritonavir monotherapy, 4 miscarried before 22 weeks' gestation, 2 changed treatment for elevated liver enzymes without virological failure, and 83 were evaluable for the main outcome. Six had virological failure confirmed on a repeat sample (median VL = 193 copies/mL; range 78-644), including two before switching to monotherapy. In these six cases, ART was intensified with tenofovir disoproxil fumarate/emtricitabine. The success rate was 75/83, 90.4% (95% CI, 81.9%-95.7%) considering two patients with VL missing at delivery as failures, and 77/83, 92.8% (95% CI, 84.9%-97.3%) when considering them as successes since both had undetectable VL on darunavir/ritonavir throughout pregnancy. In ITT, the last available VL before delivery was <50 copies/mL in all of the patients. There was no case of perinatal HIV transmission., Conclusions: Darunavir/ritonavir maintenance monotherapy required intensification in nearly 10% of cases. This limits its widespread use, thus other regimens should be evaluated in order to limit exposure to antiretrovirals, particularly NRTIs, during pregnancy., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

This study aimed to explore the research landscape of intimate partner violence (IPV)-harm-induced behavior in an intimate relationship and HIV/AIDS to determine lessons learnt and gaps that may be filled by future research. Publications related to IPV, and HIV/AIDS published from 1997 to 2019 were collected from Web of Science (WoS). STATA and VOSviewer software tools were used for bibliometric analysis. Content analysis, common topics, and the map of co-occurrence terms were structured by Latent Dirichlet allocation and VOSviewer software tool. 941 studies were included. Factors associated with domestic violence and interventions to reduce IPV were the two most common themes. Meanwhile, mental health illness among pregnant women affected by HIV and IPV, and HIV-risk among youth suffering from IPV have not received adequate attention. We suggest that more research focusing on adolescents and pregnant women affected by HIV and IPV. In addition, the development of collaborative networks between developed and developing countries should also be addressed., 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 Nguyen, Ha, Nguyen, Vu, Do, Boyer, Fond, Auquier, Latkin, Ho and Ho.)

We examined gender differences among people who inject drug (PWID) in Hai Phong, Vietnam in term of blood-borne infections, risk behaviors, and access to care. Using respondent-driven-sampling surveys, we recruited 3146 PWID from 2016 to 2018. Inclusion criteria included a positive urine test for heroin and recent injection marks. There were 155 female PWID (4,9%), including 82 at RDS-2016, 32 at RDS-2017 and 38 at RDS-2018. The age mean was 36.3 ± 7.2 years. The majority of female PWID had less than high school education (90.9%) and were unemployed (51.3%). There was no difference in the proportion of HIV and HCV positive by gender. However, women had several significant differences in risk behaviors than men in multivariable logistic regression. Being a woman was independently associated with being unemployed, being a sex worker, having unstable housing, having uses drugs for less than 5 years, more use of methamphetamine, having a partner who ever injected drugs, and less access to methadone treatment. Interventions targeting female PWID are needed, possibly through community organizations and peer educators., (© 2022. The Author(s).)

Background: Antiretroviral therapy (ART) is considered the most important intervention for HIV-positive patients; thus, encouraging the use of and adherence to ART are vital to HIV treatment outcomes. Advances in web and mobile technologies hold potential in supporting HIV treatment management., Objective: The aim of this study was to evaluate the feasibility and efficacy of a theory-based mobile health (mHealth) intervention on health behaviors and HIV treatment adherence among patients with HIV/AIDS in Vietnam., Methods: We performed a randomized controlled trial on 425 HIV patients in two of the largest HIV clinics in Hanoi, Vietnam. Both the intervention group (238 patients) and the control group (187 patients) received regular consultations with doctors and then participated in 1-month and 3-month follow-up visits. Patients in the intervention group received a theory-driven smartphone app to facilitate medication adherence and self-efficacy in HIV patients. Measurements were developed based on the Health Belief Model, which included the visual analog scale of ART Adherence, HIV Treatment Adherence Self-Efficacy Scale, and HIV Symptom Management Self-Efficacy Scale. We also included the 9-item Patient Health Questionnaire (PHQ-9) to assess patients' mental health throughout treatment., Results: In the intervention group, the adherence score increased significantly (β=1.07, 95% CI .24-1.90) after 1 month, whereas the HIV adherence self-efficacy was significantly higher after 3 months (β=2.17, 95% CI 2.07-2.27) compared to the control group. There was a positive but low level of change in risk behaviors such as drinking, smoking, and drug use. Factors related to positive change in adherence were being employed and having stable mental well-being (lower PHQ-9 scores). Factors associated with self-efficacy in treatment adherence and symptom management were gender, occupation, younger age, and having no other underlying conditions. A longer duration of ART increased treatment adherence but decreased self-efficacy in symptom management., Conclusions: Our study demonstrated that the mHealth app could improve the overall ART adherence self-efficacy of patients. Further studies with larger sample sizes and longer follow-up periods are needed to support our findings., Trial Registration: Thai Clinical Trials Registry TCTR20220928003; https://www.thaiclinicaltrials.org/show/TCTR20220928003., (©Bach Xuan Tran, Thu Minh Bui, Anh Linh Do, Laurent Boyer, Pascal Auquier, Long Hoang Nguyen, Anh Hai Tran Nguyen, Toan Van Ngo, Carl A Latkin, Melvyn W B Zhang, Cyrus S H Ho, Roger C M Ho. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.04.2023.)

Purpose: Despite antiviral therapy (ART), 800,000 deaths still occur yearly and globally due to HIV infection. In parallel with the good virological control and the aging of this population, multiple comorbidities [HIV-associated-non-AIDS (HANA) conditions] may now be observed., Methods: HIV adult patients hospitalized in intensive care unit (ICU) from all the French region from university and non-university hospital who participate to the OutcomeRea™ database on a voluntary basis over a 24-year period., Results: Of the 24,298 stays registered, 630 (2.6%) were a first ICU stay for HIV patients. Over time, the mean age and number of comorbidities (diabetes, renal and respiratory history, solid neoplasia) of patients increased. The proportion of HIV diagnosed on ICU admission decreased significantly, while the median duration of HIV disease as well as the percentage of ART-treated patients increased. The distribution of main reasons for admission remained stable over time (acute respiratory distress > shock > coma). We observed a significant drop in the rate of active opportunistic infection on admission, while the rate of active hemopathy (newly diagnosed or relapsed within the last 6 months prior to admission to ICU) qualifying for AIDS increased-nonsignificantly-with a significant increase in the anticancer chemotherapy administration in ICU. Admissions for HANA or non-HIV reasons were stable over time. In multivariate analysis, predictors of 60-day mortality were advanced age, chronic liver disease, past chemotherapy, sepsis-related organ failure assessment score > 4 at admission, hospitalization duration before ICU admission > 24 h, AIDS status, but not the period of admission., Conclusion: Whereas the profile of ICU-admitted HIV patients has evolved over time (HIV better controlled but more associated comorbidities), mortality risk factors remain stable, including AIDS status., (© 2023. The Author(s).)

Background: There has been a significant increase in methamphetamine use among persons who use drugs in Vietnam in the last 5-10 years. We examined the degree to which adherence to antiretroviral therapy (ART) mediates the relationship between recent methamphetamine use and unsuppressed HIV viral load among people who inject drugs (PWID) in Hai Phong, Vietnam., Methods: We recruited PWID from October 2016-October 2018 and enrolled HIV positive PWID into a cohort, with up to three years of total follow-up. We assessed relationships among recent methamphetamine use frequency, ART adherence and unsuppressed HIV viral load. Mediation analysis was used to estimate the total and natural direct effects of recent methamphetamine use on unsuppressed HIV viral load and the indirect effect proportion., Results: We enrolled 792 HIV seropositive PWID into the cohort; approximately 75.9% reported high/perfect ART adherence at baseline and 81.3% were virally suppressed. In mediation analysis, the total effect for the association between methamphetamine use and unsuppressed HIV viral load (1000 copies/mL) was 3.94 (95% CI: 1.95, 7.96); the natural direct effect was 2.14 (95% CI: 1.29, 3.55); the proportion mediated by self-reported ART adherence was 0.444. Similar results were found when examining lower unsuppressed HIV viral load cutpoints of 250 copies/mL and 500 copies/mL., Conclusions: Methamphetamine use is associated with unsuppressed HIV viral load among PWID despite high levels of ART adherence. Further research is needed to better understand these relationships, with emphasis on potential biological pathways that may interact with ART.

HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in human V2-apex bNAb heavy-chain precursor-expressing knock-in mice and as chimeric simian-chimpanzee immunodeficiency viruses (SCIVs) in rhesus macaques (RMs). Trimer immunization of knock-in mice induced V2-directed NAbs, indicating activation of V2-apex bNAb precursor-expressing mouse B cells. SCIV infection of RMs elicited high-titer viremia, potent autologous tier 2 neutralizing antibodies, and rapid sequence escape in the canonical V2-apex epitope. Six of seven animals also developed low-titer heterologous plasma breadth that mapped to the V2-apex. Antibody cloning from two of these animals identified multiple expanded lineages with long heavy chain third complementarity determining regions that cross-neutralized as many as 7 of 19 primary HIV-1 strains, but with low potency. Negative stain electron microscopy (NSEM) of members of the two most cross-reactive lineages confirmed V2 targeting but identified an angle of approach distinct from prototypical V2-apex bNAbs, with antibody binding either requiring or inducing an occluded-open trimer. Probing with conformation-sensitive, nonneutralizing antibodies revealed that SCIV-expressed, but not wild-type SIVcpz Envs, as well as a subset of primary HIV-1 Envs, preferentially adopted a more open trimeric state. These results reveal the existence of a cryptic V2 epitope that is exposed in occluded-open SIVcpz and HIV-1 Env trimers and elicits cross-neutralizing responses of limited breadth and potency. IMPORTANCE An effective HIV-1 vaccination strategy will need to stimulate rare precursor B cells of multiple bNAb lineages and affinity mature them along desired pathways. Here, we searched for V2-apex germ line-targeting Envs among a large set of diverse primate lentiviruses and identified minimally modified versions of one chimpanzee SIV Env that bound several human V2-apex bNAb precursors and stimulated one of these in a V2-apex bNAb precursor-expressing knock-in mouse. We also generated chimeric simian-chimpanzee immunodeficiency viruses and showed that they elicit low-titer V2-directed heterologous plasma breadth in six of seven infected rhesus macaques. Characterization of this antibody response identified a new class of weakly cross-reactive neutralizing antibodies that target the V2-apex, but only in occluded-open Env trimers. The existence of this cryptic epitope, which in some Env backgrounds is immunodominant, needs to be considered in immunogen design.

Background: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs)., Methods: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin)., Results: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers., Conclusions: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC., Clinical Trials Registration: www.clinicaltrials.gov, NCT04021290., Competing Interests: Potential conflicts of interest. J. M. L. has received honoraria or consultation fees from and participated in company-sponsored speakers bureaus for ViiV Healthcare, Gilead, and Janssen-Cilag. C. B. has received grants for an investigator-initiated study from GSK and honoraria for presentations from GSK, Gilead, and Merck Sharpe and Dohme; and has participated in advisory boards for GSK and Gilead. L. H. has received fees for participation in advisory boards or presentations from ViiV Healthcare, Merck Sharpe and Dohme, and Gilead and has received travel support for congress attendance from ViiV Healthcare, Merck Sharpe and Dohme, and Gilead. O. O. has received honoraria from ViiV Healthcare and Gilead. C. G. has received consulting fees and honoraria from ViiV Healthcare, Gilead, Merck Sharp and Dohme, and Janssen and has received support for meeting attendance from Gilead and Janssen. F. M. has received grants from ViiV Healthcare, Gilead, and Janssen, which were paid to his institution; has received honoraria from ViiV Healthcare, Gilead, Janssen, and Merck Sharp and Dohme; and has participated in data safety monitoring/advisory boards for ViiV Healthcare, Gilead, Janssen, and Merck Sharp and Dohme. S. T. has received grants for investigator-initiated studies from Gilead; has participated in and received honoraria for advisory boards or company-sponsored speakers bureaus from ViiV Healthcare, Gilead, and Merck Sharp and Dohme; has received support for registration at scientific conferences from ViiV Healthcare; and is the unpaid Medical Director of Saving Lives. E. B., C. M., B. W., M. U., G. B., and J. v. W. are employees of ViiV Healthcare and may own stock in GSK. J. O. and L. C. are employees of and may own stock in GSK. C.-Y. C. and O. D. 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) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

In the search for control of human immunodeficiency virus type 1 (HIV-1) infection without antiretroviral therapy, posttreatment controllers (PTCs) are models of HIV remission. To better understand their mechanisms of control, we characterized the HIV blood reservoirs of 8 PTCs (median of 9.4 years after treatment interruption) in comparison with those of 13 natural HIV infection controllers (HICs) (median of 18 years of infection) and with those of individuals receiving efficient antiretroviral therapy initiated during either primary HIV infection (PHIs; n  = 8) or chronic HIV infection (CHIs; n  = 6). This characterization was performed with single-genome amplification and deep sequencing. The proviral diversity, which reflects the history of past viral replication, was lower in the PTCs, PHIs, and aviremic HICs than in the blipper HICs and CHIs. The proportions of intact and defective proviruses among the proviral pool in PTCs were not significantly different from those of other groups. When looking at the quantities of proviruses per million peripheral blood mononuclear cells (PBMCs), they had similar amounts of intact proviruses as other groups but smaller amounts of defective proviruses than CHIs, suggesting a role of these forms in HIV pathogenesis. Two HICs but none of the PTCs harbored only proviruses with deletion in nef ; these attenuated strains could contribute to viral control in these participants. We show, for the first time, the presence of intact proviruses and low viral diversity in PTCs long after treatment interruption, as well as the absence of evolution of the proviral quasispecies in subsequent samples. This reflects low residual replication over time. Further data are necessary to confirm these results. IMPORTANCE Most people living with HIV need antiretroviral therapy to control their infection and experience viral relapse in case of treatment interruption, because of viral reservoir (proviruses) persistence. Knowing that proviruses are very diverse and most of them are defective in treated individuals, we aimed to characterize the HIV blood reservoirs of posttreatment controllers (PTCs), rare models of drug-free remission, in comparison with spontaneous controllers and treated individuals. At a median time of 9 years after treatment interruption, which is unprecedented in the literature, we showed that the proportions and quantities of intact proviruses were similar between PTCs and other individuals. Unlike 2/7 spontaneous controllers who harbored only nef -deleted proviruses, which are attenuated strains, which could contribute to their control, no such case was observed in PTCs. Furthermore, PTCs displayed low viral genetic diversity and no evolution of their reservoirs, indicating very low residual replication, despite the presence of intact proviruses.

Background: Antiretroviral therapy (ART) is remarkably effective in preventing perinatal transmission (PT) of HIV-1. We evaluated the PT rate in a population of women with widespread access to ART before conception., Methods: The analysis included 14 630 women with HIV-1 who delivered from 2000 to 2017 at centers participating in the nationwide prospective multicenter French Perinatal Cohort (ANRS-EPF). PT was analyzed according to time period, timing of ART initiation, maternal plasma viral load (pVL), and gestational age at birth. No infants were breastfed, and all received neonatal prophylaxis., Results: PT decreased between 3 periods, from 1.1% in 2000-2005 (58/5123) to 0.7% in 2006-2010 (30/4600) and to 0.2% in 2011-2017 (10/4907; P < .001). Restriction of the analysis to the 6316/14 630 (43%) women on ART at conception, PT decreased from 0.42% (6/1434) in 2000-2005 to 0.03% (1/3117) in 2011-2017 (P = .007). Among women treated at conception, if maternal pVL was undetectable near delivery, no PT was observed regardless of the ART combination [95%CI 0-0.07] (0/5482). Among women who started ART during pregnancy and with undetectable pVL near delivery, PT was 0.57% [95%CI 0.37-0.83] (26/4596). Among women treated at conception but with a detectable pVL near delivery, PT was 1.08% [95%CI 0.49-2.04] (9/834). We also qualitatively described 10 cases of transmission that occurred during the 2011-2017 period., Conclusions: In a setting with free access to ART, monthly pVL assessment, infant ART prophylaxis, and in the absence of breastfeeding, suppressive ART initiated before pregnancy and continued throughout pregnancy can reduce PT of HIV to almost zero., Competing Interests: Potential conflicts of interest. C. D. reports support for attending meetings and/or travel from ViiV Healthcare for conference on retroviruses and opportunistic infections registration fees. P. F. reports grants or contracts and participation on a data and safety monitoring board or advisory board from ANRS-MIE; consulting fees from MSD France and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and support for attending meetings and/or travel from MSD France, Gilead Sciences, ViiV Healthcare, Bristol Myers Squibb, and Janssen Cilag. J. G. reports grants or contracts from ViiV Healthcare and Gilead Sciences (paid to institution) and consulting fees from ViiV Healthcare, Gilead, MSD France, Astra Zeneca, Theratechnologies, and Janssen (paid to author). J. W. reports an academic grant from INSERM-ANRS and support for attending meetings and/or travel from INSERM-ANRS (academic grant). V. A.-F. reports grants or contracts from ANRS, MSD Avenir Foundation, and ViiV Healthcare (paid to institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead and ViiV Healthcare (paid to author); and support for attending meeting and/or travel from ViiV Healthcare (paid to author). 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) 2022. 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: Our objective was to identify missed opportunities for the use of pre-exposure prophylaxis (PrEP) in people with recently acquired HIV, factors associated with PrEP knowledge, and reasons for not using PrEP., Design: This was a French national cross-sectional multicentre study enrolling people diagnosed with recent HIV (incomplete Western blot or negative HIV test in the previous 6 months) in 28 HIV clinical centres. Data were gathered using a self-administered questionnaire (SAQ)., Method: We analysed missed opportunities for PrEP use via a retrospective prep cascade. Factors associated with prior knowledge of PrEP and reasons for PrEP non-use among those who knew about PrEP were described using univariate and multivariate logistic regression models., Results: Of the 224 eligible patients, 185 completed the SAQ and 168 (91%) were eligible for PrEP. Of these, 90% reported seeing at least one physician during the previous year, 26% received information about PrEP, and 5% used PrEP. Factors independently associated with a higher probability of knowing about PrEP were being a man who has sex with men, being aged 25-30 years (vs older), undergoing HIV screening at least once every semester (vs less often; odds ratio [OR] 4.11; 95% confidence interval [CI] 2.00-8.45), and practicing chemsex (OR 3.19; 95% CI 1.12-9.10). Fear of side effects and a low perceived risk of HIV infection were the two most common reasons for not using PrEP (N = 40 [33.33%] and N = 34 [28.3%], respectively)., Conclusions: We found two gaps in the retrospective PrEP cascade: insufficient provision of PrEP information by healthcare providers (mainly general practitioners) and low PrEP acceptability by informed, eligible patients. More diverse healthcare providers need to be involved in PrEP prescription, and at-risk people need to be sensitized to the risk of HIV infection., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Le 190 is a sexual health center in Paris founded in 2010. Its initial objective is to reduce the HIV/AIDS epidemic locally among men who have sex with men (MSM) through multidisciplinary support rooted in the reality of the sexuality and affective life of HIV-positive and HIV-negative MSM. Because of its constant concern for overall gay health and its community character, its activity has diversified and has enabled it to be a forerunner in both care and care pathways, on both the medical and regulatory aspects. Mental health and the complications of chemsex are taking an increasingly important place in the demand for care and the support has been adapted and perfected with the patients. Today, Le 190 is considered a model by many community actors and health professionals and is celebrating its 13th anniversary, an opportunity to share its experience and reaffirm its demonstrated benefit for public health and universal care. The major innovations of the center as well as the limitations and difficulties it has encountered will allow for a better understanding of community health in practice and more specifically gay health.

Introduction: The Prevanal study is interested in anal cancer in MSM: a rare cancer linked in 90 % of cases to an infection with the human papillomavirus (HPV). Sexually transmitted despite the use of a condom, it affects in particular HIV-positive MSM who are considered a particularly exposed group., Purpose of Research: It aims above all to translate an epidemiological problem into a socio-anthropological question focused on sexuality and gender identities. The challenge is to develop a multidimensional approach to this emerging and resurgent health issue among MSM., Results: In this period of biomedicalization of HIV prevention and the predicted end of AIDS, the notion of pleasure or risk associated with the anus as a sexual organ has remained a blind spot in research and must be placed at the center of investigation and analysis., Conclusions: The cultural dimension of the obstacles to the prevention, diagnosis and care of anal cancer among MSM needs to be documented, while identifying the simultaneous unthought of their sexual desires and their health needs.