Discriminatory experiences among gay, bisexual, and other men who have sex with men, and transgender and non-binary individuals: a cross sectional analysis.

Background: Several systems of oppression combine in complex ways to impact the lives of minority populations. Following an intersectionality framework, we assessed the frequency and perceived reasons for discrimination among gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender and non-binary individuals (TGNB), stratified by race. Methods: Online survey among MSM and TGNB ≥18 years living in Brazil, between November/2021 and January/2022. We used the 18-item Explicit Discrimination Scale to assess day-to-day experiences of differential treatment, and perceived discrimination. For each item, participants indicated their perceived reasons for differential treatment using 14 pre-defined options. Negative binomial regression models assessed if race was a significant predictor of discrimination. Subsequent models, stratified by race, examined associations of perceived reasons and number of reasons with perceived discrimination. Findings: Of 8464 MSM and TGNB, 4961 (58.6%) were White, 2173 (25.7%) Pardo (Brazil's official term for admixed populations), and 1024 (12.1%) Black. Black participants' scores for perceived discrimination (mean, standard deviation) were higher (10.2, 8.8) [Pardo (6.5, 6.8), White (5.2, 5.7)], and race was both the main reason for and the strongest predictor of perceived discrimination. The number of reasons participants used to interpret their discriminatory experiences was also a predictor of discrimination score among White, Pardo, and Black participants. Interpretation: LGBTQIA+phobia was highly prevalent among all participants. Additionally, our results indicated that Black MSM and TGNB participants were more frequently discriminated against than other racial groups, with racial discrimination uniquely contributing these experiences. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.

COVID-19 vaccine efficacy in participants with weakened immune systems from four randomized-controlled trials.

BACKGROUND: Although the SARS-CoV-2 vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. METHODS: A post-hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, COVID-19 vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS (NTIS) individuals starting at 14 days after completion of the primary series through the blinded phase for each of the four trials. An analysis of participants living with well-controlled HIV was conducted using the same methods. RESULTS: 3,852/30,351 (12.7%) Moderna participants, 3,088/29,868 (10.3%) Novavax participants, 3,549/32,380 (11.0%) AstraZeneca participants, and 5,047/43,788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (versus placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants vs NTIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with HIV. CONCLUSIONS: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared to those with non-tempered immune systems in the four COVID-19 vaccine randomized controlled efficacy trials.

Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial.

Background: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results: Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/µL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. Conclusions: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS.

HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial.

OBJECTIVE: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. DESIGN: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. METHODS: HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. RESULTS: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. CONCLUSION: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.

Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics.

BACKGROUND: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. METHODS: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. RESULTS: A total of 202 PLWH with CD4 ≥ 200 cells/µL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. CONCLUSIONS: 17DD was safe and well-tolerated in PLWH with CD4 ≥ 200 cells/µL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Knowledge of HIV transmission, prevention strategies and U = U among adult sexual and gender minorities in Brazil.

INTRODUCTION: Although strong scientific evidence of the efficacy and effectiveness of treatment-as-prevention (TasP) is available, full endorsement of the "Undetectable = Untransmittable" (U = U) and "zero-risk" messages could be improved. Increasing knowledge about HIV transmission, prevention and treatment is a critical component of care efforts. The study assessed knowledge of HIV transmission and prevention strategies, and the perceived accuracy of the slogan U = U among sexual and gender minorities (SGM) in Brazil. METHODS: Cross-sectional web-based survey targeting adult SGM living in Brazil (2021-2022) recruited on social media and dating apps. We used the 12-item HIV Knowledge Assessment (HIV-KA) questionnaire to assess HIV knowledge, three items of which address pre-exposure prophylaxis (PrEP), post-exposure prophylaxis and TasP. Perceived accuracy of the U = U slogan was assessed with the question: "With regards to HIV-positive individuals transmitting HIV through sexual contact, how accurate do you believe the slogan U = U is?". We a priori grouped the study population into three mutually exclusive groups: people living with HIV (PLHIV), HIV negative and HIV unknown. We used logistic regression models to assess factors associated with high HIV knowledge and perception of the U = U as completely accurate. RESULTS: Of 50,222 individuals accessing the questionnaire, 23,981 were included: 5071 (21.0%) PLHIV, 17,257 (71.5%) HIV negative and 1653 (6.9%) HIV unknown. The proportion of participants with high knowledge was significantly higher for PLHIV and HIV negative (48.1% and 45.5%, respectively) compared to 26.1% of HIV unknown. More PLHIV perceived U = U as completely accurate (80.4%), compared to 60.0% of HIV negative and 42.9% of HIV unknown. HIV knowledge correlates with perceived accuracy of the U = U slogan across all groups. Higher HIV knowledge was associated with higher income and education regardless of HIV status. Among HIV-negative participants, PrEP awareness and use were associated with higher knowledge and accurate perception of the U = U slogan. CONCLUSIONS: Our findings show that HIV knowledge and perceived accuracy of U = U are strongly correlated, that knowledge differs according to HIV status, and that poor socio-economic is linked to poor knowledge among SGM from Brazil. Educational strategies regarding TasP, U = U and zero risk targeting socio-economically vulnerable populations are urgent in Brazil.

Variability in life expectancy among people with HIV in Brazil by gender and sexual orientation.

INTRODUCTION: In Brazil, though Antiretroviral Therapy (ART) is available to all, the benefits may not be experienced uniformly. We projected Life Expectancy (LE) for People Living with HIV (PLHIV) in care as currently observed and estimated the impact of guideline-concordant care. METHODS: Using a microsimulation model, we projected LE for a cohort of PLHIV and for four population groups: cisgender Men who have Sex with Men (MSM), cisgender Men who have Sex with Women (MSW), Cisgender Women (CGW), and Transgender Women (TGW). Cohort data from Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation (INI/Fiocruz) informed model parameters. We modeled five scenarios: 1) Current care: ART initiation, adherence, and retention in care as currently observed, 2) Guideline-concordant care: immediate ART initiation, full adherence to treatment, and consistent retention in care, 3) Immediate ART initiation with observed adherence to treatment and retention in care, 4) Full adherence to treatment with observed timing of ART initiation and retention in care, and 5) Consistent retention in care with observed timing of ART initiation and adherence. RESULTS: With current care, LE from age 15 would be 45.9, 44.4, 54.2, and 42.3 years, for MSM, MSW, CGW, and TGW. With guideline-concordant care, LE would be 54.2, 54.4, 63.1, and 53.2 years, for MSM, MSW, CGW and TGW, with TGW experiencing the greatest potential increase in LE (10.9 years). When investigating the components of care separately, MSW and CGW would gain most LE with immediate ART initiation, whereas for MSM and TGW consistent retention in care would be most impactful. CONCLUSIONS: In settings like INI/Fiocruz, MSW and CGW would benefit most from interventions focused on earlier diagnosis and linkage to care, whereas TGW and MSM would benefit from interventions to sustain engagement in care. Assessment of the HIV care continuum for specific populations should inform care priorities.

Frailty and health-related quality of life among older people living with HIV pre- and post-COVID-19 pandemic onset: A cross-sectional study.

INTRODUCTION: Antiretroviral therapy increased the survival and life expectancy of People living With HIV (PWH). Frailty-related syndromes among older PWH (aged 50+ years) may affect their Health-related Quality of Life (HQoL). Additionally, the COVID-19 pandemic has impacted health-related outcomes. This study aimed to estimate the prevalence of frailty and pre-frailty among older PWH, and to explore associations of HQoL with the study assessment period and frailty status. METHODS: Cross-sectional study conducted pre- (23-Mar-2019 to 5-Mar-2020) and post-COVID-19 pandemic onset (23-Jun-2021 to 5-May-2022), among older PWH at INI-Fiocruz, the largest cohort of PWH in Rio de Janeiro, Brazil. We measured frailty using Fried assessment, consisting of five domains: unintentional weight loss; self-reported exhaustion, weakness, slow walking speed, low physical activity. HQoL was assessed using the ACTG SF-21, which contains 21 questions divided into 8 domains. We used Chi-Square test, Fisher's exact test, Kruskal-Wallis and ranksum test for comparisons. RESULTS: We included 250 older PWH: 109 (43.6 %) pre- and 141 (56.4 %) post-COVID-19 pandemic onset. Median age was 60-years (IQR: 55‒64). Most self-identified as cisgender men 152 (60.8 %), Pardo/Black 146 (58.4 %), with completed secondary education or less 181 (72.7 %) and low income 132 (52.8 %). Overall, prevalence of frailty and pre-frailty were 9.2 % (95 % CI: 8.1‒10.3) and 61.6 % (95 % CI: 54.0‒69.2). Prevalence of frailty in the pre- and pos-COVID-19 pandemic periods were 7.3 % and 10.6 % (p = 0.66). HQoL scores were lower among participants with frailty compared to those with non-frailty and pre-frailty in all eight domains, and among those included in the post-COVID-19 compared to pre-COVID-19 period for four domains. CONCLUSIONS: We observed low prevalence of frailty, but high prevalence of pre-frailty among older PWH. Frailty status did not differ according to the COVID-19 assessment period. Assessment of frailty and HQoL should be incorporated in clinical practice for older PWH. Programs to reverse or prevent frailty should be implemented within the public health system.

Smoking Cessation Is Associated With Short-Term Improvement of Vascular Health in a Cohort of People Living With HIV in Rio de Janeiro, Brazil.

Smoking is highly prevalent in people living with HIV/AIDS (PLHA), leading to detrimental effects in different tissues. We examined the effects of nicotine replacement therapy (NRT) on smoking cessation and vascular health. From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking. The primary outcome was endothelial function measured by brachial artery flow-mediated dilatation (FMD). We evaluated the percent change in FMD compared to the baseline measure (Δ%FMD) to detect improvements among participants who quit smoking. To confirm the results, we used linear regression models to account for classical cardiovascular (CV) confounders. We included 117 participants with median age of 45.5 years (IQR= 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes, almost half were smoking 20+ cigarettes/day (41.7%). After 12 weeks 30.76% participants quit smoking. Comparison of Δ%FMD change from baseline to week 12 showed that among participants adherent to therapy, there has been an increase in Δ%FMD when compared to those who relapsed (1.17% [0.29-2.98] vs -0.19% [-1.95-0.91], p<0.001). After adjustment for CV factors, multiple linear regression showed that Δ%FMD in participants who quit smoking presented a 2.54 mean increase in comparison to those who continued smoking (p=0.007). In conclusion, this study provides evidence that a strategy of NRT and counseling is modestly effective for smoking cessation in PLHA and improves vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering the incidence of future cardiovascular events.

Frailty and health-related quality of life among older people living with HIV pre- and post-COVID-19 pandemic onset: A cross-sectional study

ABSTRACT Introduction: Antiretroviral therapy increased the survival and life expectancy of People living With HIV (PWH). Frailty-related syndromes among older PWH (aged 50+ years) may affect their Health-related Quality of Life (HQoL). Additionally, the COVID-19 pandemic has impacted health-related outcomes. This study aimed to estimate the prevalence of frailty and pre-frailty among older PWH, and to explore associations of HQoL with the study assessment period and frailty status. Methods: Cross-sectional study conducted pre- (23-Mar-2019 to 5-Mar-2020) and post-COVID-19 pandemic onset (23-Jun-2021 to 5-May-2022), among older PWH at INI-Fiocruz, the largest cohort of PWH in Rio de Janeiro, Brazil. We measured frailty using Fried assessment, consisting of five domains: unintentional weight loss; self-reported exhaustion, weakness, slow walking speed, low physical activity. HQoL was assessed using the ACTG SF-21, which contains 21 questions divided into 8 domains. We used Chi-Square test, Fisher's exact test, Kruskal-Wallis and ranksum test for comparisons. Results: We included 250 older PWH: 109 (43.6 %) pre- and 141 (56.4 %) post-COVID-19 pandemic onset. Median age was 60-years (IQR: 55‒64). Most self-identified as cisgender men 152 (60.8 %), Pardo/Black 146 (58.4 %), with completed secondary education or less 181 (72.7 %) and low income 132 (52.8 %). Overall, prevalence of frailty and pre-frailty were 9.2 % (95 % CI: 8.1‒10.3) and 61.6 % (95 % CI: 54.0‒69.2). Prevalence of frailty in the pre- and pos-COVID-19 pandemic periods were 7.3 % and 10.6 % (p = 0.66). HQoL scores were lower among participants with frailty compared to those with non-frailty and pre-frailty in all eight domains, and among those included in the post-COVID-19 compared to pre-COVID-19 period for four domains. Conclusions: We observed low prevalence of frailty, but high prevalence of pre-frailty among older PWH. Frailty status did not differ according to the COVID-19 assessment period. Assessment of frailty and HQoL should be incorporated in clinical practice for older PWH. Programs to reverse or prevent frailty should be implemented within the public health system.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics

ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Variability in life expectancy among people with HIV in Brazil by gender and sexual orientation

Abstract Introduction In Brazil, though Antiretroviral Therapy (ART) is available to all, the benefits may not be experienced uniformly. We projected Life Expectancy (LE) for People Living with HIV (PLHIV) in care as currently observed and estimated the impact of guideline-concordant care. Methods Using a microsimulation model, we projected LE for a cohort of PLHIV and for four population groups: cisgender Men who have Sex with Men (MSM), cisgender Men who have Sex with Women (MSW), Cisgender Women (CGW), and Transgender Women (TGW). Cohort data from Evandro Chagas National Institute of Infectious Diseases/Oswaldo Cruz Foundation (INI/Fiocruz) informed model parameters. We modeled five scenarios: 1) Current care: ART initiation, adherence, and retention in care as currently observed, 2) Guideline-concordant care: immediate ART initiation, full adherence to treatment, and consistent retention in care, 3) Immediate ART initiation with observed adherence to treatment and retention in care, 4) Full adherence to treatment with observed timing of ART initiation and retention in care, and 5) Consistent retention in care with observed timing of ART initiation and adherence. Results With current care, LE from age 15 would be 45.9, 44.4, 54.2, and 42.3 years, for MSM, MSW, CGW, and TGW. With guideline-concordant care, LE would be 54.2, 54.4, 63.1, and 53.2 years, for MSM, MSW, CGW and TGW, with TGW experiencing the greatest potential increase in LE (10.9 years). When investigating the components of care separately, MSW and CGW would gain most LE with immediate ART initiation, whereas for MSM and TGW consistent retention in care would be most impactful. Conclusions In settings like INI/Fiocruz, MSW and CGW would benefit most from interventions focused on earlier diagnosis and linkage to care, whereas TGW and MSM would benefit from interventions to sustain engagement in care. Assessment of the HIV care continuum for specific populations should inform care priorities.

Mpox severity and associated hospitalizations among people with HIV and related immunosuppression in Brazil.

OBJECTIVES: This study aimed to analyze characteristics of mpox hospitalization in a Brazilian cohort, further exploring the impact of HIV on mpox-related outcomes and hospitalization. DESIGN: We conducted a descriptive analysis, comparing characteristics of individuals diagnosed with mpox according to hospitalization and HIV status, and described the mpox cases among those living with HIV. METHODS: This was a single-center, prospective cohort study conducted at a major infectious diseases referral center in Rio de Janeiro, Brazil, that enrolled participants older than 18 years of age diagnosed with mpox. Information was collected on standardized forms, including data on sociodemographic, behavioral, clinical and laboratory characteristics. For comparisons, we used chi-squared, Fisher's exact and the Moods median tests whenever appropriate. RESULTS: From June to December, 2022, we enrolled 418 individuals diagnosed with mpox, of whom 52% were people with HIV (PWH). PWH presented more frequently with fever, anogenital lesions and proctitis. The overall hospitalization rate was 10.5% ( n  = 43), especially for pain control. Among hospitalized participants, PWH had more proctitis and required invasive support. Mpox severity was related to poor HIV continuum of care outcomes and low CD4 + cell counts. All deaths ( n  = 2) occurred in PWH with CD4 + less than 50 cells/µl. CONCLUSION: HIV-related immunosuppression likely impacts mpox clinical outcomes. This is of special concern in settings of poor adherence and late presentation to care related to socioeconomic inequalities, such as Brazil. The HIV continuum of care must be taken into account when responding to the mpox outbreak.

Recent HIV infection and annualized HIV incidence rates among sexual and gender minorities in Brazil and Peru (ImPrEP seroincidence study): a cross-sectional, multicenter study.

Background: HIV incidence estimation is critical for monitoring the HIV epidemic dynamics and the effectiveness of public health prevention interventions. We aimed to identify sexual and gender minorities (SGM) with recent HIV infections, factors associated with recent HIV infection, and to estimate annualised HIV incidence rates. Methods: Cross-sectional multicentre study in HIV testing services in Brazil and Peru (15 cities). Inclusion criteria: 18+ years, SGM assigned male at birth, not using pre-/post-exposure prophylaxis. We identified recent HIV infection using the Maxim HIV-1 LAg-Avidity EIA assay as part of a recent infection testing algorithm (RITA). Annualized HIV incidence was calculated using the UNAIDS/WHO incidence estimator tool. Multivariable logistic regression models were used to estimate factors associated with recent HIV infection. Trial registration: NCT05674682. Findings: From 31-Jan-2021 to 29-May-2022, 6899 individuals participated [Brazil: 4586 (66.5%); Peru: 2313 (33.5%)]; 5946 (86.2%) cisgender men, 751 (10.9%) transgender women and 202 (2.9%) non-binary/gender diverse. Median age was 27 (IQR: 23-34) years. HIV prevalence was 11.4% (N = 784/6899); 137 (2.0%) SGM were identified with recent HIV infection. The overall annualized HIV incidence rate was 3.88% (95% CI: 2.86-4.87); Brazil: 2.62% (95% CI: 1.78-3.43); Peru: 6.69% (95% CI: 4.62-8.69). Participants aged 18-24 years had higher odds of recent HIV infection compared to those aged 30+ years in both countries. Interpretation: Our results highlight the significant burden of HIV epidemic among SGM in large urban centres of Brazil and Peru. Public health policies and interventions to increase access to effective HIV prevention methods such as PrEP are urgently needed in Latin America. Funding: Unitaid, WHO (Switzerland), Ministry of Health from Brazil and Peru.

Differential gene expression of cytokines, receptors, and miRNAs in individuals living with HIV-1 and vaccinated against yellow fever.

Between 2016 and 2018, Brazil faced a yellow fever (YF) outbreak, which led to an expansion of vaccination coverage. The coexistence of the YF outbreak and the HIV-1 epidemic in Brazil raised concerns regarding the immune response and vaccine effectiveness in individuals living with HIV (PLWH). The aim of this study was to investigate the immune response to YF vaccination in PLWH and HIV-uninfected individuals as controls. Transcript levels of immunomodulatory molecules, including IL-6, IL-10, IL-21, TGF-ß, CD19, CD163, miR-21, miR-146, and miR-155, were measured using RTqPCR. TCD4+ cells were evaluated by cytometry, and neutralizing antibody (Nab) titers were detected by a micro plaque-reduction neutralization test. The findings of our study revealed several noteworthy observations. First, there was a notable reduction in the circulation of TCD4+ cells postvaccination. Among people living with HIV (PLWH), we observed an increase in the expression of IL-10 following vaccination, while IL-6 expression was diminished in PLWH with lower TCD4+ counts. Furthermore, we identified the downregulation of CD19 and TGF-ß, along with the upregulation of IL-21 and CD163. Notably, we observed positive correlations between the levels of IL-10/IL-21, IL-10/CD163, and IL-6/CD19. Additionally, there was a positive correlation between miRNAs 146 and 155. It is important to emphasize that all participants exhibited robust neutralizing antibody responses after receiving 17DD YF vaccination. In this context, the gene expression data presented can be useful for biomarker studies of protective antibodies induced by YF vaccination. This study sheds light on immune mechanisms in individuals living with HIV and YF vaccination.

Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial.

BACKGROUND: Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study. METHODS: The HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094. FINDINGS: Of the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation. INTERPRETATION: Long-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance. FUNDING: Division of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.

Characteristics of women diagnosed with mpox infection compared to men: A case series from Brazil.

BACKGROUND: Cisgender men were mostly affected during the 2022 mpox multinational outbreak, with few cases reported in women. This study compares the characteristics of individuals diagnosed with mpox infection according to gender in Rio de Janeiro. METHODS: We obtained surveillance data of mpox cases notified to Rio de Janeiro State Health Department (June 12 to December 15, 2022). We compared women (cisgender or transgender) to men (cisgender or transgender) using chi-squared, Fisher's exact, and Mood's median tests. RESULTS: A total of 1306 mpox cases were reported; 1188 (91.0%) men (99.8% cisgender, 0.2% transgender), 108 (8.3%) women (87.0% cisgender, 13.0% transgender), and 10 (0.8%) non-binary persons. Compared to men, women were more frequently older (40+years: 34.3% vs. 25.1%; p < 0.001), reported more frequent non-sexual contact with a potential mpox case (21.4% vs. 9.8%; p = 0.004), fewer sexual partnerships (10.9 vs. 54.8%; p < 0.001), less sexual contact with a potential mpox case (18.5% vs. 43.0%; p < 0.001), fewer genital lesions (31.8% vs. 57.9%; p < 0.001), fewer systemic mpox signs/symptoms (38.0% vs. 50.1%; p = 0.015) and had a lower HIV prevalence (8.3% vs. 46.3%; p < 0.001), with all cases among transgender women. Eight women were hospitalized; no deaths occurred. The highest number of cases among women were notified in epidemiological week 34, when the number of cases among men started to decrease. CONCLUSIONS: Women diagnosed with mpox presented differences in epidemiological, behavioral, and clinical characteristics compared to men. Health services should provide a comprehensive assessment that accounts for gender diversity.