Contemporary HIV-1 consensus Env with AI-assisted redesigned hypervariable loops promote antibody binding.

An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against highly diverse Envelope glycoproteins (Env). Since Env with the longest hypervariable (HV) loops is more resistant to the cognate bnAbs than Env with shorter HV loops, we redesigned hypervariable loops for updated Env consensus sequences of subtypes B and C and CRF01_AE. Using modeling with AlphaFold2, we reduced the length of V1, V2, and V5 HV loops while maintaining the integrity of the Env structure and glycan shield, and modified the V4 HV loop. Spacers are designed to limit strain-specific targeting. All updated Env are infectious as pseudoviruses. Preliminary structural characterization suggests that the modified HV loops have a limited impact on Env's conformation. Binding assays show improved binding to modified subtype B and CRF01_AE Env but not to subtype C Env. Neutralization assays show increases in sensitivity to bnAbs, although not always consistently across clades. Strikingly, the HV loop modification renders the resistant CRF01_AE Env sensitive to 10-1074 despite the absence of a glycan at N332.

Clinical, molecular, and drug resistance epidemiology of HIV in Jordan, 2019-2021: a national study.

BACKGROUND: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control. METHODS: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Among 231 (70%) participants, most were male (184/80%), and from Jordan (217/94%). Among 188 treatment-experienced-participants (>6 months), 165 (88%) were virally suppressed. High level resistance was most frequent against nucleoside reverse transcriptase inhibitor (13/81%), and integrase-strand transfer inhibitor (INSTI) (10/62%) drugs among viremic (≥1,000 HIV copies/mL) treatment-experienced participants with drug resistant mutations (DRMs, n=16). Common HIV subtypes (n=43) were B (6/14%), A1 (5/12%), and CRF01_AE (5/12%); additionally, novel recombinant forms were detected. In multivariate analysis, independently higher risk for late diagnosis (n=49) was observed with diagnosis through blood donation (vs check-up: RR 2·20, 95%CI 1·16-4·17) and earlier time-period of diagnosis (1986-2014 vs 2015-2021: RR 2·87, 95%CI 1·46-5·62). CONCLUSIONS: Late diagnosis and INSTI resistance endanger national HIV prevention and treatment in Jordan - high-level resistance to INSTI suggests therapeutic drug monitoring is needed for treatment efficacy, and conservation of treatment options.

Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa.

BACKGROUND: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings. METHODS: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in five sub-Saharan African countries included people without HIV (PWOH, n = 249) and people living with HIV (PLWH, n = 250). Adult participants received one of two accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein-specific binding antibody responses). Binding antibody responders were defined as participants with a > 2.5-fold increase from baseline or the lower limit of quantification if negative at baseline. RESULTS: The mean age was 33.4 years, 52% of participants were female, and among PLWH, the median (interquartile range) CD4+ cell count was 560.0 (418.0-752.0) cells/µL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units (EU)/mL in PWOH; 2509 EU/mL in PLWH), and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PLWH). At 12 months post-dose 2, GMCs in PWOH and PLWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen. CONCLUSIONS: Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PLWH in Africa. TRIAL REGISTRATION: NCT02598388.

Cumulative exposure to depressive symptoms and all-cause mortality among adults living with HIV in Kenya, Nigeria, Tanzania, and Uganda.

OBJECTIVE: :We estimated the effects of cumulative exposure to depressive symptoms on risk of all-cause mortality among people living with HIV in four African countries. DESIGN: :Analysis of prospective cohort data. METHODS: :The African Cohort Study (AFRICOS) is a prospective cohort of people receiving care at twelve clinics in Kenya, Nigeria, Tanzania, and Uganda. Every six months from January 2013 to May 2020, participants underwent laboratory monitoring, structured surveys, and assessment of depressive symptom severity using the Center for Epidemiologic Studies Depression Scale (CES-D). All-cause mortality was the outcome of interest. The predictor of interest was a time-updated measure of the percentage of days lived with depression (PDD). Marginal structural Cox proportional hazards regression models were used, adjusting for potential confounders including time-varying alcohol use, drug use, and viral load. RESULTS: :Among 2520 enrolled participants, 1479 (59%) were women and the median age was 38 (interquartile range [IQR]: 32-46). At enrollment, 1438 (57%) were virally suppressed (<200 copies/mL) and 457 (18%) had CES-D ≥ 16, indicating possible depression. Across 9093 observed person-years, the median PDD was 0.7% (IQR: 0-5.9%) with 0.8 deaths per 100 person-years. Leading causes of death included cancer (18% of deaths) and accidents (14%). Models suggested that each 25% absolute increase in PDD was associated with a 69% increase in the risk of all-cause mortality (HR: 1.69; 95% CI: 1.18-2.43). CONCLUSIONS: :Cumulative exposure to depressive symptoms was substantially associated with the risk of mortality in this cohort of PLWH in Africa.

Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials.

Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.

Advanced HIV disease in East Africa and Nigeria, in The African Cohort Study.

BACKGROUND: Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 count of <200 cells per cubic millimeter or clinical sequelae. We assessed factors associated with AHD among people living with HIV before and during the "test and treat" era. SETTING: The African Cohort Study prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. METHODS: Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios and 95% confidence intervals for factors associated with CD4 count of <200 cells per cubic millimeter at study visits. RESULTS: From 2013 to 2021, 3059 people living with HIV with available CD4 at enrollment were included; median age was 38 years [interquartile range: 30-46 years], and 41.3% were men. From 2013 to 2021, the prevalence of CD4 count of <200 cells per cubic millimeter decreased from 10.5% to 3.1%, whereas the percentage on ART increased from 76.6% to 100% ( P <0.001). Factors associated with higher odds of CD4 count of <200 cells per cubic millimeter were male sex (adjusted odds ratio 1.56 [confidence interval: 1.29 to 1.89]), being 30-39 years (1.42 [1.11-1.82]) or older (compared with <30), have World Health Organization stage 2 disease (1.91 [1.48-2.49]) or higher (compared with stage 1), and HIV diagnosis eras 2013-2015 (2.19 [1.42-3.37]) or later (compared with <2006). Compared with ART-naive, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 count of <200 cells per cubic millimeter (<6 months on ART: 0.45 [0.34-0.58]). CONCLUSION: With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk.

Prevalence of Urogenital Mycoplasma genitalium Infection at 2 US Army Medical Facilities.

BACKGROUND: Sexually transmitted infections (STIs) have a high incidence in the US Armed Forces and can adversely impact service members' ability to perform their duties. Better knowledge of Mycoplasma genitalium (MG) epidemiology in the military is needed to understand the potential impact of this emerging pathogen on force readiness. METHODS: We conducted cross-sectional analyses of data from US Army service members and other Military Health System beneficiaries participating in a trial of an STI/HIV behavioral intervention at Fort Liberty, NC, and Joint Base Lewis-McChord, WA. At enrollment, participants completed questionnaires and provided biological specimens for nucleic acid amplification testing for MG, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG). We used principal component analysis and robust Poisson regression to examine associations between participant characteristics and prevalent urogenital MG. RESULTS: Among 432 participants enrolled between November 2020 and February 2023, 43 had MG (prevalence, 10.0%), of whom 13 had coinfection with another bacterial STI (all 13 were positive for CT, with 1 also positive for NG). The prevalence of MG was significantly higher among female (13.5%) versus male (7.6%; P = 0.048) participants and non-Hispanic Black (14.9%) versus non-Hispanic White participants (6.6%; P = 0.045). Single relationship status and increased number of recent sexual partners were correlated, and their component was associated with higher MG prevalence (adjusted prevalence ratio, 2.11; 95% confidence interval, 1.29-3.48). CONCLUSIONS: The high prevalence of urogenital MG among Military Health System beneficiaries highlights the importance of understanding the potential clinical sequelae of MG and conducting additional epidemiologic research in military settings.

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production.

The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.

HIV prevalence and awareness among adults presenting for enrolment into a study of people at risk for HIV in Kisumu County, Western Kenya.

INTRODUCTION: Despite declines in new HIV diagnoses both globally and in Kenya, parts of Western Kenya still report high HIV prevalence and incidence. We evaluated HIV prevalence to inform the development of policies for strategic and targeted HIV prevention interventions. METHODS: Adult participants aged 18-35 years were recruited in Kisumu County and screened for HIV for a prospective HIV incidence cohort. Questionnaires assessed HIV-associated risk behaviors. Participants who tested positive for HIV were disaggregated into groups based on prior knowledge of their HIV status: previously-diagnosed and newly-diagnosed. In separate analyses by prior knowledge, robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with a positive HIV test in each group, as compared to participants without HIV. RESULTS: Of 1059 participants tested for HIV, 196 (18.5%) had a positive HIV test. Among PLWH, 78 (39.8%) were newly diagnosed with HIV at screening. After adjusting for other variables, previously-diagnosed HIV was more common among females than males (PR 2.70, 95%CI 1.69-4.28), but there was no observed sex difference in newly-diagnosed HIV prevalence (PR 1.05, 95%CI 0.65-1.69). Previously-diagnosed HIV was also more common among people reporting consistent use of condoms with primary sexual partners as compared to inconsistent condom use (PR 3.19, 95%CI 2.09-4.86), but newly-diagnosed HIV was not associated with such a difference between consistent and inconsistent condom use (PR 0.73, 95%CI 0.25-2.10). CONCLUSION: Prevalence of newly-diagnosed HIV was high, at approximately 8% of participants, and not statistically different between genders, highlighting the need for improved HIV case finding regardless of sex. The higher prevalence of previously-diagnosed HIV in female participants may reflect higher rates of HIV testing through more encounters with the healthcare system. Higher prevalence of consistent condom use amongst those previously-diagnosed suggests behavioral change to reduce HIV transmission, a potential benefit of policies to facilitate earlier HIV diagnosis.

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing.

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel "block-lock-stop" approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

Implications of asymptomatic malaria infections on hematologic parameters in adults living with HIV in malaria-endemic regions with varying transmission intensities.

OBJECTIVES: HIV and malaria coinfection impacts disease management and clinical outcomes. This study investigated hematologic abnormalities in malaria-asymptomatic people living with HIV (PLHIV) in regions with differing malaria transmission. METHODS: Study participants were enrolled in the African Cohort Study: two sites in Kenya, one in Uganda, and one in Nigeria. Data was collected at enrollment and every 6 months. Logistic regression estimated odds ratios for associations between HIV/malaria status and anemia, thrombocytopenia, and leucopenia. RESULTS: Samples from 1587 participants with one or more visits comprising 1471 (92.7%) from PLHIV and 116 (7.3%) without HIV were analyzed. Parasite point prevalence significantly differed across the study sites (P <0.001). PLHIV had higher odds of anemia, with males at lower odds compared to females; the odds of anemia decreased with age, reaching significance in those ≥50 years old. Participants in Kisumu, Kenya had higher odds of anemia compared to other sites. PLHIV had higher odds of leucopenia, but malaria co-infection was not associated with worsened leucopenia. The odds of thrombocytopenia were decreased in HIV/malaria co-infection compared to the uninfected group. CONCLUSION: Hematological parameters are important indicators of health and disease. In PLHIV with asymptomatic malaria co-infection enrolled across four geographic sites in three African countries, abnormalities in hematologic parameters differ in different malaria transmission settings and are region-specific.

Safety, tolerability, and immunogenicity of the Ebola Sudan chimpanzee adenovirus vector vaccine (cAd3-EBO S) in healthy Ugandan adults: a phase 1, open-label, dose-escalation clinical trial.

BACKGROUND: Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available. METHODS: In this phase 1, open-label, dose-escalation trial we evaluated the safety, tolerability, and immunogenicity of a monovalent chimpanzee adenovirus 3 vaccine against Sudan Ebola virus (cAd3-EBO S) at Makerere University Walter Reed Project in Kampala, Uganda. Study participants were recruited from the Kampala metropolitan area using International Review Board-approved written and electronic media explaining the trial intervention. Healthy adults without previous receipt of Ebola, Marburg, or cAd3 vectored-vaccines were enrolled to receive cAd3-EBO S at either 1 × 1010 or 1 × 1011 particle units (PU) in a single intramuscular vaccination and were followed up for 48 weeks. Primary safety and tolerability endpoints were assessed in all vaccine recipients by reactogenicity for the first 7 days, adverse events for the first 28 days, and serious adverse events throughout the study. Secondary immunogenicity endpoints included evaluation of binding antibody and T-cell responses against the Sudan Ebola virus glycoprotein, and neutralising antibody responses against the cAd3 vector at 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT04041570, and is completed. FINDINGS: 40 healthy adults were enrolled between July 22 and Oct 1, 2019, with 20 receiving 1 × 1010 PU and 20 receiving 1 × 1011 PU of cAd3-EBO S. 38 (95%) participants completed all follow-up visits. The cAd3-EBO S vaccine was well tolerated with no severe adverse events. The most common reactogenicity symptoms were pain or tenderness at the injection site (34 [85%] of 40), fatigue (29 [73%] of 40), and headache (26 [65%] of 40), and were mild to moderate in severity. Positive responses for glycoprotein-specific binding antibodies were induced by 2 weeks in 31 (78%) participants, increased to 34 (85%) participants by 4 weeks, and persisted to 48 weeks in 31 (82%) participants. Most participants developed glycoprotein-specific T-cell responses (20 [59%, 95% CI 41-75] of 34; six participants were removed from the T cell analysis after failing quality control parameters) by 4 weeks after vaccination, and neutralising titres against the cAd3 vector were also increased from baseline (90% inhibitory concentration of 47, 95% CI 30-73) to 4 weeks after vaccination (196, 125-308). INTERPRETATION: The cAd3-EBO S vaccine was safe at both doses, rapidly inducing immune responses in most participants after a single injection. The rapid onset and durability of the vaccine-induced antibodies make this vaccine a strong candidate for emergency deployment in Sudan Ebola virus outbreaks. FUNDING: National Institutes of Health via interagency agreement with Walter Reed Army Institute of Research.

Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo.

Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during acute infection by correlating host gene expression with viral RNA abundance within individual cells. Wide sequencing of cells from one participant with the highest plasma viral load revealed that intracellular viral RNA transcription correlates inversely with expression of the gene PTMA, which encodes prothymosin α. This association was genome-wide significant (Padjusted < 0.05) and was validated in 28 additional participants from Thailand and the Americas with HIV-1 CRF01_AE and subtype B infections, respectively. Overexpression of prothymosin α in vitro confirmed that this cellular factor inhibits HIV-1 transcription and infectious virus production. Our results identify prothymosin α as a host factor that restricts HIV-1 infection in vivo, which has implications for viral transmission and cure strategies.

Achieving the third 95 in sub-Saharan Africa: application of machine learning approaches to predict viral failure.

OBJECTIVE: Viral failure in people with HIV (PWH) may be influenced by multiple sociobehavioral, clinical, and context-specific factors, and supervised learning approaches may identify novel predictors. We compared the performance of two supervised learning algorithms to predict viral failure in four African countries. DESIGN: Cohort study. METHODS: The African Cohort Study is an ongoing, longitudinal cohort enrolling PWH at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. Participants underwent physical examination, medical history-taking, medical record extraction, sociobehavioral interviews, and laboratory testing. In cross-sectional analyses of enrollment data, viral failure was defined as a viral load at least 1000 copies/ml among participants on antiretroviral therapy (ART) for at least 6 months. We compared the performance of lasso-type regularized regression and random forests by calculating area under the curve (AUC) and used each to identify factors associated with viral failure; 94 explanatory variables were considered. RESULTS: Between January 2013 and December 2020, 2941 PWH were enrolled, 1602 had been on antiretroviral therapy (ART) for at least 6 months, and 1571 participants with complete case data were included. At enrollment, 190 (12.0%) had viral failure. The lasso regression model was slightly superior to the random forest in its ability to identify PWH with viral failure (AUC: 0.82 vs. 0.75). Both models identified CD4 + count, ART regimen, age, self-reported ART adherence and duration on ART as important factors associated with viral failure. CONCLUSION: These findings corroborate existing literature primarily based on hypothesis-testing statistical approaches and help to generate questions for future investigations that may impact viral failure.

Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability.

OBJECTIVES: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability. DESIGN: RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (group 1) or were boosted with ALVAC-HIV and AIDSVAX (group 2) or only AIDSVAX alone (group 3) 24 weeks after completing the RV144 series. METHODS: Plasma samples from RV306 study participants were used to measure antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses. RESULTS: Additional boosting increased the magnitude of all Fc-mediated effector functions 2 weeks following the additional boost compared with 2 weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24-26 weeks after the last vaccination for the study participants receiving an additional boost compared with those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared with 2 weeks after completing the RV144 regimen. CONCLUSION: Additional boosting of RV144 improved the magnitude but not the durability of some Fc-mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone.

The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.

Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

OBJECTIVE: We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. METHODS: The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. RESULTS: Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). CONCLUSIONS: Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

Food and Water Insecurity in Sexual and Gender Minority Groups Living With HIV in Lagos, Nigeria.

BACKGROUND: Food and water insecurity are associated with poor health outcomes that may be exacerbated by social marginalization and barriers to health care experienced by sexual and gender minorities (SGM) in resource-limited settings. We explored factors associated with food and water insecurity in SGM with HIV. SETTING: A longitudinal study of 357 men who have sex with men, transgender women, and other gender-identifying people in Lagos, Nigeria. METHODS: Laboratory testing, interviews, food and water assessments, and anthropometry were performed quarterly. Robust Poisson regression with generalized estimating equations was used to evaluate factors potentially associated with food and water insecurity. RESULTS: From 2014 to 2018, 357 SGM with HIV completed either the food or water assessments. At baseline, participants identified as cisgender men who have sex with men 265 (74.2%), transgender women 63 (17.7%), or as nonbinary/other gender 29 (8.1%). Food insecurity and water insecurity were reported by 63/344(18.3%) and 113/357(31.7%), respectively, at any visit. Food and water insecurity each decreased with ongoing study participation. Food insecurity was associated with nonpartnered relationship status, CD4 count <500 cells/mm 3 , and lack of access to piped water. Water insecurity was associated with age 25 years or older, living with a man, transactional sex, and food insecurity. CONCLUSIONS: Food and water insecurity were common among SGM in Nigeria and decreased with continued study participation, suggesting amenability to intervention when SGM are successfully engaged in care. Targeted interventions to support food and water security may improve HIV-related outcomes, such as CD4 count.

Brain volumetrics differ by Fiebig stage in acute HIV infection.

OBJECTIVE: People with chronic HIV exhibit lower regional brain volumes compared to people without HIV (PWOH). Whether imaging alterations observed in chronic infection occur in acute HIV infection (AHI) remains unknown. DESIGN: Cross-sectional study of Thai participants with AHI. METHODS: One hundred and twelve Thai males with AHI (age 20-46) and 18 male Thai PWOH (age 18-40) were included. Individuals with AHI were stratified into early (Fiebig I-II; n  = 32) and late (Fiebig III-V; n  = 80) stages of acute infection using validated assays. T1-weighted scans were acquired using a 3 T MRI performed within five days of antiretroviral therapy (ART) initiation. Volumes for the amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus were compared across groups. RESULTS: Participants in late Fiebig stages exhibited larger volumes in the nucleus accumbens (8% larger; P  = 0.049) and putamen (19%; P  < 0.001) when compared to participants in the early Fiebig. Compared to PWOH, participants in late Fiebig exhibited larger volumes of the amygdala (9% larger; P  = 0.002), caudate nucleus (11%; P  = 0.005), nucleus accumbens (15%; P  = 0.004), pallidum (19%; P  = 0.001), and putamen (31%; P  < 0.001). Brain volumes in the nucleus accumbens, pallidum, and putamen correlated modestly with stimulant use over the past four months among late Fiebig individuals ( P s < 0.05). CONCLUSIONS: Findings indicate that brain volume alterations occur in acute infection, with the most prominent differences evident in the later stages of AHI. Additional studies are needed to evaluate mechanisms for possible brain disruption following ART, including viral factors and markers of neuroinflammation.