BACKGROUND:Antiretroviral therapies with long dosing intervals have the potential to improve virological outcomes and treatment satisfaction for people with HIV-1. We report the primary endpoint results from week 48 of ISLEND-2, a phase 3 trial evaluating the efficacy and safety of switching to once-weekly oral islatravir-lenacapavir from daily oral standard of care in virologically suppressed adults with HIV-1. METHODS:This randomised, open-label, active-controlled, phase 3 non-inferiority trial was conducted at 100 sites in 14 countries and territories. Eligible participants were adults (aged ≥18 years) with HIV-1 who had been virologically suppressed on daily oral standard-of-care treatment for at least 6 months and had no previous virological failure. Participants were randomly assigned (1:1), using interactive response technology and stratified by geographical region, antiretroviral class, and CD4+ T-cell count, to switch to the once-weekly, single-tablet oral regimen of islatravir (2 mg)-lenacapavir (300 mg) or to continue daily oral standard of care for at least 96 weeks. The primary endpoint was the proportion of participants with an HIV-1 RNA viral load of 50 copies per mL or higher at week 48 (as per the US Food and Drug Administration-defined Snapshot algorithm), with a non-inferiority margin of 4%, assessed in all randomly assigned participants who received any dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT06630299, and is active but closed to new participants. FINDINGS:From Oct 8, 2024, to April 30, 2025, 727 participants were screened, of whom 647 were eligible for the study, 634 were randomly assigned, and 626 received treatment: 314 with islatravir-lenacapavir and 312 with standard of care. Of 626 participants, 211 (34%) were female, 193 (31%) were Black, 119 (19%) were Asian, 123 (20%) were Hispanic or Latine, and 89 (14%) were aged 65 years or older. At baseline, 552 (88%) were on a single-tablet antiretroviral regimen and 478 (76%) were receiving regimens containing integrase strand transfer inhibitors. At week 48, one (0·3%) of 314 participants in the islatravir-lenacapavir group and four (1·3%) of 312 participants in the standard-of-care group had an HIV-1 RNA viral load of 50 copies per mL or higher (difference -1·0% [95·002% CI -3·0 to 1·1]), meeting the non-inferiority criteria. Treatment-related adverse events occurred in 58 (18%) of 314 participants in the islatravir-lenacapavir group and one (<1%) of 312 participants in the standard-of-care group. Two (1%) of 314 participants in the islatravir-lenacapavir group and one (<1%) of 312 participants in the standard-of-care group discontinued the study owing to adverse events, with adverse events of grade 3 or higher occurring in 24 (8%) and 28 (9%) participants and serious adverse events in 22 (7%) and 27 (9%) participants in the islatravir-lenacapavir group and standard-of-care group, respectively. There were three deaths: one in the islatravir-lenacapavir group and two in the standard-of-care group, none of which were considered treatment-related. INTERPRETATION:Once-weekly islatravir-lenacapavir showed non-inferior efficacy to the standard of care and was generally well tolerated. Longer-term safety data will provide further valuable insights beyond the week 48 data presented here. Islatravir-lenacapavir has potential to be the first once-weekly complete oral single-tablet regimen for HIV-1 treatment. FUNDING:Gilead Sciences and Merck Sharp & Dohme.

Transgender women (TW) bear high HIV and syphilis burden, but little is known about their partners (PTW). We conducted a cross-sectional study at a voluntary HIV-testing center in Argentina (June/2023–January/2025). PTW were individuals reporting sex with TW, regardless of other partners’ genders. We compared sociodemographic and behavioral characteristics and HIV and syphilis prevalence among PTW, men who have sex with men (MSM), and TW. We included 211 PTW, 1715 MSM, and 152 TW. PTW median age was 30 years and 65

BACKGROUND:Single-tablet regimens (STRs) revolutionised HIV-1 treatment, improving adherence and clinical outcomes; however, many people cannot take these due to resistance, contraindications, or drug-drug interactions, instead relying on complex multi-tablet regimens. Novel STRs are therefore needed. We aimed to evaluate the efficacy and safety of a novel STR, bictegravir-lenacapavir, in people with HIV-1. METHODS:ARTISTRY-1 was a randomised, open-label, active-controlled, non-inferiority phase 3 trial conducted at hospitals and clinics across 15 countries that enrolled people with HIV-1 with virological suppression on complex regimens. Participants were randomly assigned (using interactive technology, 2:1, stratified by geographical region) to switch to once-daily oral bictegravir-lenacapavir 75 mg/50 mg STR or continued complex regimen. The primary outcome was the proportion of participants with an HIV-1 RNA viral load of 50 copies per mL or higher at week 48 (US Food and Drug Administration Snapshot algorithm), assessed in all randomly assigned participants who received any dose of assigned treatment. This trial (active; enrolment complete) was registered with ClinicalTrials.gov (NCT05502341). FINDINGS:Between Jan 29 and Sept 26, 2024, 729 participants were screened; 557 were randomly assigned and treated (bictegravir-lenacapavir n=371; complex regimen n=186). At baseline, median age was 60 years (range 22-84), HIV treatment duration was 28 years (IQR 22-32); participants were taking a median of three antiretroviral pills per day (range 2-11). At week 48, an HIV-1 RNA viral load of 50 copies per mL or higher was observed in three (1%) participants receiving bictegravir-lenacapavir and two (1%) receiving a complex regimen (difference -0·3%; 95·002% CI -2·3 to 1·8), meeting the non-inferiority margin of 4%. No resistance emerged. Adverse event rates were similar between groups. Six (2%) participants discontinued bictegravir-lenacapavir and one (1%) discontinued their complex regimen due to adverse events. There were five deaths in the bictegravir-lenacapavir group, none of which were deemed related to study drug. Participants reported increased treatment satisfaction after switching to bictegravir-lenacapavir. INTERPRETATION:Bictegravir-lenacapavir STR demonstrated non-inferior efficacy to complex regimens, with a similar safety profile and increased treatment satisfaction. Bictegravir-lenacapavir offers new opportunities for HIV-1 treatment optimisation for people taking complex regimens. FUNDING:Gilead Sciences.

BACKGROUND:Innovative HIV-1 therapies, especially those with infrequent dosing, are a promising approach to advance progress toward the UNAIDS goal of ending HIV-1 transmission. VH4011499 (VH-499) is a new capsid inhibitor in development as a long-acting antiretroviral agent for HIV-1 treatment. We present the antiviral effect, pharmacokinetics, safety, and tolerability of oral VH-499 from a proof-of-concept phase 2a trial in people with HIV-1. METHODS:The randomized, double-blind, placebo-controlled CINNAMON trial evaluated oral VH-499 monotherapy in adults naive to antiretroviral therapy (ART) with viremia. During a 10-day monotherapy period, participants received VH-499 25, 100, or 250 mg or placebo on Days 1 and 6. After monotherapy, participants initiated locally sourced standard-of-care ART starting on Day 11. The primary endpoint was maximum change from baseline in viral load through Day 11. Secondary endpoints included exposure-response relationship, safety, and tolerability. RESULTS:Twenty-three participants were enrolled (VH-499, n=20; placebo, n=3). Viral load decreased through Day 11 for all VH-499 dose groups (mean [SD] maximum decline: 25 mg, -1.8 [0.5]; 100 mg, -1.8 [0.5]; 250 mg, -2.2 [0.4]). Increasing VH-499 exposures were associated with greater viral load declines. Ninety-five percent (19/20) of participants had no emergent genotypic resistance-associated mutations. Adverse events (AEs) were mild or moderate in severity, and no serious AEs or AEs leading to withdrawal were reported. CONCLUSIONS:VH-499 monotherapy demonstrated highly potent antiviral activity, was well tolerated, and had a favorable safety profile. These results support further development of VH-499 as part of a complete long-acting regimen for HIV-1 treatment (ClinicalTrials.gov, NCT06039579).

ABSTRACT Introduction Latin America is a key region in advancing efforts to end the HIV epidemic globally. Despite breakthroughs in HIV treatment and prevention in the last 20 years, as well as region‐wide improvements in health infrastructure and policies, there has been a 13% increase in new acquisitions in Latin America from 2010 to 2024. The Caribbean, Central and South America network for HIV epidemiology (CCASAnet), established in 2006, is one of seven regions in the International epidemiology Databases to Evaluate AIDS (IeDEA). CCASAnet contributes substantially to regional science and the development of national and region‐wide policies. Here, we describe data sources and operational methodologies employed by CCASAnet, as well as the current state of the cohort. Methods CCASAnet data are collected using standardized data elements, including demographic information, HIV disease history, laboratory data, antiretroviral regimens, co‐infections and comorbidities. Data collection has expanded to include prospective data such as substance use, antiretroviral therapy adherence, geriatric syndromes and tuberculosis treatment. All clinical sites retain ownership of their data, and CCASAnet data contribute as able to global IeDEA‐level projects. Robust data quality initiatives and statistical methods have strengthened the cohort. Results CCASAnet consists of nine clinics across seven countries (Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru). Over 61,000 adults and children living with HIV have contributed observational data through December 2023. While CD4 at enrolment has remained largely unchanged, time to antiretroviral therapy initiation has decreased, retention in care has improved and the proportion with undetectable HIV RNA has dramatically increased. Co‐infections and AIDS‐defining malignancies remain a cause of morbidity and mortality, but non‐communicable diseases have also increased. Overall mortality trends in the region have improved over time, with some notable exceptions. Conclusions Underscoring the importance of maintaining longitudinal collaborations and data collection, CCASAnet remains the largest source of high‐quality data for HIV epidemiology in Latin America and serves as an important evidence base for informing global and regional policy and stakeholder decisions related to the HIV epidemic.

BACKGROUND:Dolutegravir (DTG)/lamivudine dual therapy (DT) has demonstrated noninferiority to triple therapy (TT) in the GEMINI trials. Although the population with ≤200 CD4 cells/mm3 had a lower response rate, this was unrelated to virological failure. This trial evaluated the antiviral activity of dolutegravir/lamivudine among antiretroviral therapy (ART)-naive patients with human immunodeficiency virus (HIV) with a CD4 count ≤200 cells/mm3. METHODS:DOLCE is a randomized, hypothesis-based, open-label, multicenter study l, assessing the antiviral efficacy of DTG/3TC at week 48 in treatment-naive people with HIV (PWH) with CD4 counts ≤200 cells/mm3. Participants were randomly assigned in a 2:1 ratio to receive DTG/3TC as a single tablet regimen or DTG plus Tenofovir disoproxil fumarate (TDF)/XTC: Emtricitabine or lamivudine (FTC or 3TC). The primary endpoint was the proportion of participants with pVL <50 copies/mL at week 48 (Food and Drug Administration snapshot analysis intent-to-treat exposed population). This report presents results at week 48. RESULTS:Baseline characteristics were similar in both arms. In the DT arm, median CD4 cell count was 109 cells/mm (interquartile range [IQR]: 49-177) and median pVL was 180,000 copies/mL (IQR: 53 309-468 691); 45.4% had CD4 <100 cells/mm3, and 61.4% had pVL >100 000 copies/mL. CDC (Centers for Disease Control and Prevention) stage C: 31.4%. At week 48, virological suppression (pVL <50 copies/mL) was achieved 82.2% in the DT (125/152), and the CD4 count increased by +200 cells/mm3. Per-protocol analysis showed a response rate of 91.9%. Severe adverse events (n = 17) were reported in 15 of 152 participants (11.1%). CONCLUSIONS:Dolutegravir/3TC demonstrated high efficacy in a population with low CD4 counts and high viral load. This study adds information regarding the efficacy and safety of DTG/3TC, regardless of baseline CD4 counts and viral load. CLINICAL TRIALS REGISTRATION:NCT04880395.

Abstract Background Innovative human immunodeficiency virus (HIV) therapies, especially those with infrequent dosing, are a promising approach to advance progress toward the UNAIDS goal of ending HIV transmission. VH4011499 (VH-499) is a new capsid inhibitor in development as a long-acting antiretroviral agent for HIV-1 treatment. We present the antiviral effect, pharmacokinetics, safety, and tolerability of oral VH-499 from a proof-of-concept phase 2a trial in people with HIV-1. Methods The randomized, double-blind, placebo-controlled CINNAMON trial evaluated oral VH-499 monotherapy in adults naive to antiretroviral therapy (ART) with viremia. During a 10-day monotherapy period, participants received VH-499 25, 100, or 250 mg or placebo on Days 1 and 6. After monotherapy, participants initiated locally sourced standard-of-care ART starting on Day 11. The primary endpoint was maximum change from baseline in viral load through Day 11. Secondary endpoints included exposure–response relationship, safety, and tolerability. Results Twenty-three participants were enrolled (VH-499, n = 20; placebo, n = 3). Viral load decreased through Day 11 for all VH-499 dose groups (mean [SD] maximum decline: 25 mg, −1.8 [0.5]; 100 mg, −1.8 [0.5]; 250 mg, −2.2 [0.4]). Increasing VH-499 exposures were associated with greater viral load declines. Ninety-five percent (19/20) of participants had no emergent genotypic resistance-associated mutations. Adverse events (AEs) were mild or moderate in severity, and no serious AEs or AEs leading to withdrawal were reported. Conclusions VH-499 monotherapy demonstrated highly potent antiviral activity, was well tolerated, and had a favorable safety profile. These results support further development of VH-499 as part of a complete long-acting regimen for HIV-1 treatment. Clinical Trials Registration NCT06039579.

Background Human papillomavirus (HPV) is a common sexually transmitted infection, with higher prevalence among men who have sex with men (MSM) and people who self-identify as transgender women (PSTGW). High-risk genotypes (hrHPV) carry oncogenic potential. This study assessed hrHPV prevalence in penile samples from MSM and PSTGW in Buenos Aires, Argentina. Methods A cross-sectional analysis of baseline data from a longitudinal study was conducted. Participants aged ≥18 were recruited from an HIV prevention center. Penile samples, collected via standardized sandpaper exfoliation, were analyzed using the AmpFire HPV Genotyping Assay for 15 genotypes. Logistic regression models identified factors associated with HPV. Results Among 298 samples from 300 participants (256 MSM, 44 PSTGW), HIV prevalence was 27%. Penile hrHPV prevalence was 31%, with no significant difference between MSM and PSTGW (p = 0.465). Frequent genotypes included HPV-33, HPV-53 and HPV-16 (6.3%, 5.3%, and 4.6% respectively). People with HIV (PWH) showed higher hrHPV prevalence than HIV negative individuals (41% vs 27%, p = 0.023), more infections with ≥3 genotypes (15% vs 4%, p < 0.001), and higher nonavalent vaccine genotype detection (30% vs 15%, p = 0.005). Multivariate analysis associated hrHPV infection with being PWH (aOR = 1.99), >5 sexual partners in the past month (aOR = 1.77), and lifetime sex work (aOR = 2.68). Conclusions Penile hrHPV was highly prevalent among MSM and PSTGW, particularly among PWH and those with a history of sex work. Low vaccination rate and high prevalence of vaccine-preventable genotypes underscore the need to expand HPV vaccination in these populations.

Abstract Background Long-acting cabotegravir+rilpivirine (CAB+RPV LA) and dolutegravir+lamivudine (DTG/3TC) are HIV-1 antiretroviral therapy regimens with different administration routes and dosing frequencies, allowing for greater choice. Methods VOLITION is a Phase 3b, multicenter, non-randomized, parallel-group, open-label implementation–effectiveness study (NCT05917509) evaluating viral suppression on DTG/3TC for up to 16 weeks, followed by a participant-determined optional switch to CAB+RPV LA dosed Q2M or continuation of DTG/3TC through Month (M) 11/12. Co-primary endpoints were the time to virologic suppression with DTG/3TC and the proportion of participants with HIV-1 RNA <50 copies/mL per the Snapshot algorithm at M11 with CAB+RPV LA. Safety and participant experience were also assessed. Results 171 participants initiated DTG/3TC. Median time to suppression on DTG/3TC was 4.1 weeks (95% confidence interval: 4.1–4.3), with 98% (n=167/171) achieving virologic suppression and similar rates observed across baseline viral load and CD4+ cell count categories. At Day of Choice (DoC), 85% (n=129/151) of eligible participants chose to switch to CAB+RPV LA. At M11, 113/129 (88%) participants maintained suppression with CAB+RPV LA; one participant had confirmed virologic failure with resistance (INSTI and NNRTI). Both regimens were well tolerated, with no new safety signals observed. Treatment satisfaction improved after DoC and remained high with CAB+RPV LA. Conclusions Providing treatment-naive participants with the option to switch to CAB+RPV LA as soon as virologic suppression was achieved on daily oral therapy allowed them to choose a treatment to meet their individualized needs while maintaining virologic suppression, which is essential for long-term treatment success and optimized quality of life. Clinical Trial Registration NCT05917509

BACKGROUND:Despite higher risk of poorer outcomes and potential sub-optimal vaccine effectiveness, people living with HIV (PLWH) are underrepresented in SARS-CoV-2 vaccine trials. We evaluated the safety and immunogenicity of the Ad5-nCoV vaccine (CanSino Biologics Inc./The Beijing Institute of Biotechnology) in PLWH. METHODS:In this single arm, open-label Phase 2b trial, PLWH were enrolled in Argentina. Participants received two doses of Ad5-nCoV vaccine (intramuscular, dosage 5x1010 viral particles) at days 0 and 56. The primary outcomes were safety as serious adverse events [SAE], solicited and unsolicited local and systemic adverse events, impact on HIV viral load and CD4 counts and immunogenicity measured by S-RBD IgG and pseudo-virus neutralizing antibodies (nAbs) up to 52 weeks (ClinicalTrials.gov:NCT05005156). FINDINGS:Between June 2021-January 2022, 140 PLWH received at least one dose of Ad5-nCoV vaccine. At baseline, the majority were on antiretroviral therapy (99.3%), virologically suppressed (93.6%), with a median (IQR) CD4-cell count:736 (531-946) cells/ul. At baseline, 38 (27%) participants were seropositive for S-RBD antibodies, and 40 (28%) for nAbs. There were no SAEs related to the vaccine. Solicited AE within 7 days after first and second dose occurred in 93 (69%) and 75 (60%) participants, mostly grade 1, included pain, drowsiness and headache. The incidence of unsolicited AE within 28 days of vaccination was 10.7%. There were no significant changes in plasma viral load, CD4 count, CD4/CD8 ratio and no new AIDS-defining illnesses were reported. There were significant increases in the geometric mean titers (GMT) of S-RBD and nAbs between baseline to week 52. Seroconversion rates 28 days after the first and second doses (day 84) were 80% and 94% for S-RBD, and 35% and 78% for nAbs. INTERPRETATION:The Ad5-nCoV vaccine was safe and induced an adequate immune response in virologically suppressed PLWH, maintaining high antibody titers at least during the first year post-vaccination. No significant changes were observed in plasma viral load, CD4 count and CD4/CD8 ratio.

BACKGROUND:Doravirine/islatravir is an investigational regimen that is being studied for human immunodeficiency virus type 1 (HIV-1) treatment. METHODS:In this phase 3, double-blind, double-dummy trial (ClinicalTrials.gov NCT04233879), previously untreated adults with HIV-1 were randomized (1:1) and stratified by HIV-1 RNA (≤/>100 000 copies/mL) and CD4 count (</≥200 cells/µL) to doravirine/islatravir (100/0.75 mg) or bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) orally once-daily (primary endpoint: percentage of participants with HIV-1 RNA <50 copies/mL at week 48; US Food and Drug Administration snapshot, 10% noninferiority margin). RESULTS:Overall, 597 participants were treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. Doravirine/islatravir was noninferior to bictegravir/emtricitabine/tenofovir alafenamide: 265 of 298 (88.9%) versus 264 of 299 (88.3%) had HIV-1 RNA <50 copies/mL (difference, 0.5%; 95% confidence interval [CI]: -4.7, 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference, -50; 95% CI: -79, -21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 × 109/L (difference, -0.20; 95% CI: -0.30, -0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with coronavirus disease 2019 being most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs that led to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria that required discontinuation for decreased CD4 and lymphocyte counts. CONCLUSIONS:Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped. CLINICAL TRIALS REGISTRATION:NCT04233879.

BACKGROUND:Definitions of virological failure and treatment discontinuation for long-acting injectable (LAI) cabotegravir and rilpivirine antiretroviral therapy are inconsistent in clinical practice and observational studies, which complicates interpretation and implementation of findings. The CONSENSUS-LAI study aimed to establish consistent definitions of virological failure and treatment discontinuation to enhance evidence transferability and support optimal clinical outcomes. METHODS:The study had two phases. Phase 1 was an international online survey exploring existing definitions of virological and treatment discontinuation, conducted between April 25 and July 1, 2024. Eligible participants were health-care professionals working in infectious disease or sexual health services who had provided care to at least ten people living with HIV in the past 6 months, had prescribed LAI cabotegravir and rilpivirine in clinical trials or clinical practice, and were able to give informed consent. Participants were recruited via social media and mailing lists of medical specialist societies. Phase 2 was a Delphi process, in which a panel of experts, selected to ensure representation from all six WHO regions, scored leading definitions from phase 1 on a 9-point Likert scale. The proposed definitions were scored according to four validity criteria: clarity, usability in the expert's setting, appropriateness across clinical purposes, and applicability across relevant population groups. Revisions were suggested in iterative rounds until consensus was reached. Consensus was predefined as at least 75% of experts agreeing or strongly agreeing (scores 7-9) with the validity criteria. FINDINGS:386 LAI cabotegravir and rilpivirine prescribers across 28 countries completed the survey, revealing 15 definitions for virological failure on LAI cabotegravir and rilpivirine and nine for treatment discontinuation. 52 experts participated in the Delphi process. Consensus agreement on both definitions was reached after two rounds for all validity criteria. For virological failure, the consensus definition was as follows: (a) viral load 200 copies or more per mL or more on two occasions 2-4 weeks apart, or (b) a single viral load of more than 1000 copies per mL, and/or (c) emergent resistance, in the context of timely injections and prior suppression of less than 200 copies per mL, OR (d) unable to suppress viral load to less than 200 copies per mL on continuous therapy. For treatment discontinuation the consensus definition was as follows: people on LAI cabotegravir and rilpivirine who have missed two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation. INTERPRETATION:The consensus definitions provide a foundation for aligning practice and evaluating patient outcomes. Further validation of the viral load threshold for virological failure and the optimal viral load retesting window is required. FUNDING:ViiV Healthcare.

BACKGROUND:There is a high unmet need for effective HIV prevention options, including vaccines, for individuals at high risk of HIV acquisition who choose not to use pre-exposure prophylaxis or other prevention strategies. This study evaluated the efficacy and safety of an HIV-1 vaccine regimen consisting of tetravalent mosaic adenovirus serotype 26-based vaccine (Ad26.Mos4.HIV) and bivalent clade C glycoprotein (gp) 140-mosaic gp140 vaccine, in a population with high seroincidence. METHODS:This randomised, double-blind, phase 3 trial enrolled adult cisgender men and transgender individuals without HIV from 52 academic medical centres, health departments, and community-based clinics in Latin America, Europe, and the USA. Participants were randomly assigned (1:1) by use of a centrally prepared, computer-generated randomisation schedule to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks. Study participants, study site personnel (except for those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked from vaccine allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140-mosaic gp140 at months 6 and 12. The primary endpoint was vaccine efficacy in preventing HIV-1 acquisition between months 7 and 24 or between months 7 and 30 in the per-protocol population, which included all randomly assigned participants who received at least one study vaccination and who had not been diagnosed with HIV-1 4 weeks after the third vaccination, had received all planned vaccinations at the first three vaccination visits within the respective visit windows, and had no major protocol deviations linked to incorrect product administration. Safety outcomes were assessed in all randomised participants who received at least one study vaccination. The trial is registered with ClinicalTrials.gov (NCT03964415) and is complete. FINDINGS:Between Nov 4, 2019, and Aug 13, 2021, 3900 participants were enrolled and randomly assigned; 3887 received at least one study vaccination (1942 assigned to vaccine, 1945 to placebo). 3870 (99·6%) of 3887 participants were assigned male at birth, seven (0·2%) were assigned female, and one participant's sex at birth was undifferentiated; 3557 (91·5%) participants identified as male gender, 48 (1·2%) as female gender, and 278 (7·2%) as transgender or non-binary. The per-protocol population included 1525 participants in the vaccine group and 1494 in the placebo group. From month 7 to month 24 in the per-protocol population, HIV-1 incidence per 100 person-years was 3·63 (95% CI 2·77 to 4·67) in the vaccine group and 3·35 (2·53 to 4·36) in the placebo group, with an estimated vaccine efficacy (months 7-24) of -0·7% (95% CI -50·9 to 32·8; p=0·97). Vaccine efficacy (months 7-30) was -149·1% (-737·7 to 26·0; p=0·14). Most solicited local and systemic adverse events were mild or moderate and short-lived. Medically attended adverse events occurred in 999 (51·4%) of 1942 participants given vaccine and 1002 (51·5%) of 1945 participants given placebo; serious adverse events occurred in 82 (4·2%) of 1942 participants given vaccine and 77 (4·0%) of 1945 participants given placebo. No fatal adverse events considered related to the study vaccine occurred. Adverse events of special interest (thrombotic events or thrombocytopenia) occurred in four participants with vaccine and two with placebo; none had thrombosis with thrombocytopenia syndrome. INTERPRETATION:The lack of efficacy in this and other HIV vaccine trials points to the importance of current efforts to develop vaccines that generate broadly neutralising antibodies. FUNDING:Johnson & Johnson; HIV Vaccine Trials Network; Division of AIDS, a division of National Institute of Allergy and Infectious Diseases; and US Army Medical Materiel Development Activity, a subordinate command of the US Army Medical Research and Development Command.

Background Although Argentina provides access to no cost HIV care, treatment adherence and retention in care remain suboptimal. This study aimed to explore factors associated with self-reported adherence and appointment attendance over time. Method Participants ( N = 360) were people living with HIV (PLWH) that were lost to care (i.e., three missed pharmacy pickups in the last 6 months, or had not attended a physician visit in the last 12 months). Participants were recruited from seven HIV clinics in four urban centers in Argentina and re-engaged in care. Demographic variables, predictors, i.e., alcohol use, self-efficacy, motivation, patient-provider communication, insurance type (private/public), and outcomes, i.e., missed infectious disease (ID) specialist appointments, other missed clinic and lab appointments, and self-reported adherence were assessed over 2 years. A logistic regression and Poisson regression model within a generalized linear mixed model framework was used to analyze the association between predictors, treatment adherence outcomes, and interactions with time. Results Following re-engagement in care, increased alcohol use was associated with lower odds of antiretroviral therapy adherence over time, increased odds of missing ID specialist appointments, and missed clinic/lab appointments. Self-efficacy was associated with better medication adherence and fewer missed ID specialist appointments over time. Similarly, both motivation and patient/provider communication were associated with fewer missed ID specialist and clinic/lab appointments over time. Having private health insurance was also associated with less missed clinic/lab appointments. Conclusion Findings suggest alcohol use reduction interventions could improve treatment outcomes in this population. Additionally, interventions targeting patient-provider communication and patient self-efficacy and motivation may enhance retention following re-engagement in care.