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.

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.

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.

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.

HIV-1 envelope diversity and sensitivity to broadly neutralizing antibodies across stages of acute HIV-1 infection.

We studied the relationship between viral diversity and susceptibility to broadly neutralizing antibodies (bNAbs) in longitudinal plasma and peripheral blood mononuclear cells from 89 people with HIV who initiated antiretroviral therapy (ART) during acute and early HIV-1 infection (AEHI). HIV-1 diversity and predicted bNAb susceptibility were comparable across AEHI. Diversity evolution was not observed during ART, suggesting (pro)viruses at initiation or during treatment may identify individuals with susceptible virus for bNAb interventional trials.

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.

Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States.

Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.

HIV prevalence in transgender populations and cisgender men who have sex with men in sub-Saharan Africa 2010-2022: a meta-analysis.

Introduction: The Global AIDS Strategy 2021-2026 calls for equitable and equal access to HIV prevention and treatment programmes for all populations to reduce HIV incidence and end HIV/AIDS as a public health threat by 2030. Transgender populations (TGP), including transmen (TGM) and transwomen (TGW) are populations that have been marginalised and are at high risk of HIV infection in sub-Saharan Africa (SSA). Limited surveillance data on HIV among TGP are available in the region to guide programmatic responses and policymaking. Surveillance data on cisgender men who have sex with men (cis-MSM) are comparatively abundant and may be used to infer TGP HIV prevalence. Methods: Data from key population surveys conducted in SSA between 2010-2022 were identified from existing databases and survey reports. Studies that collected HIV prevalence on both TGP and cis-MSM populations were analysed in a random effect meta-analysis to estimate the ratio of cis-MSM:TGW HIV prevalence. Results: Eighteen studies were identified encompassing 8,052 TGW and 19,492 cis-MSM. TGW HIV prevalence ranged from 0-71.6% and cis-MSM HIV prevalence from 0.14-55.7%. HIV prevalence in TGW was 50% higher than in cis-MSM (prevalence ratio (PR) 1.50 95% CI 1.26-1.79). TGW HIV prevalence was highly correlated with year/province-matched cis-MSM HIV prevalence (R2 = 0.62), but poorly correlated with year/province-matched total population HIV prevalence (R2 = 0.1). Five TGM HIV prevalence estimates were identified ranging from 1-24%. Insufficient TGM data were available to estimate cis-MSM:TGM HIV prevalence ratios. Conclusion: Transgender women experience a significantly greater HIV burden than cis-MSM in SSA. Bio-behavioural surveys designed and powered to measure determinants of HIV infection, treatment coverage, and risk behaviours among transgender populations, distinct from cis-MSM, will improve understanding of HIV risk and vulnerabilities among TGP and support improved programmes.

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.

Human Mpox in People Living with HIV: Epidemiologic and Clinical Perspectives from Nigeria.

Sub-Saharan Africa (SSA) is disproportionately affected by mpox and HIV. We described epidemiologic trends and clinical experiences in the management of mpox in people living with HIV (PLWH) in Nigeria and further examined how the rapidly accumulating body of knowledge from the 2022 global mpox outbreak might be explored to improve mpox care in PLWH in SSA. During the 2017/2018 Nigerian mpox outbreak, we reported that 9/40 (22.5%) hospitalized mpox patients with known HIV status were PLWH. In the 2022 global mpox outbreak, 52% of confirmed mpox cases with known HIV status were PLWH, predominantly sexual and gender minority groups. However, substantial missing data on HIV status of confirmed mpox cases highlights a critical gap in HIV testing as a component of mpox management. Before 2022, sexual activity was not commonly linked to mpox transmission, but this was identified as a major driver of transmission during the 2022 mpox outbreak. Notable sexual history observed in Nigerian mpox patients in 2017/2018 suggests that the contribution of sexual activity in human-to-human mpox transmission might have been underappreciated for years. Our cohort of PLWH with mpox, predominantly individuals with advanced or uncontrolled HIV, were significantly more likely to experience severe mpox manifestations and prolonged disease compared with those without HIV. This contrasts with the generally less remarkable differences in mpox presentation between people with and without HIV in Western countries, an observation that can be at least partially explained by more stable HIV disease. The unavailability of mpox antiviral drugs and vaccines in SSA highlights global inequity in mpox response, which requires an urgent attention. As mpox countermeasures become available in SSA, lessons learned from their use in Western countries could provide important guidance for care providers in SSA. Public health measures to mitigate stigmatization in PLWH with mpox is also critical.

Unique HIV Risk Factors and Prevention Needs for Transgender Women and Cisgender Men Who Have Sex with Men in Bangkok, Thailand.

Background: Transgender women (TGW) and cisgender men who have sex with men (cis-MSM) are often grouped together as key populations. We evaluated behavioral and other characteristics that may distinguish TGW from cis-MSM in Bangkok, Thailand. Methods: We enrolled into an 18-month cohort cis-MSM and TGW 18-35 years of age without HIV, who reported anal intercourse plus condomless anal intercourse, multiple partners, transactional sex, and/or sexually transmitted infection. Robust multivariable Poisson regression was used to estimate adjusted prevalence ratios (aPRs) and confidence intervals (95% CIs) for associations with being a TGW. Among TGW, logistic regression with generalized estimating equations was used to estimate adjusted odds ratios (aORs) and 95% CIs for associations with taking hormones and having undergone gender affirmation surgery (GAS). Results: From 2017 to 2019, 660 cis-MSM and 348 TGW were enrolled. Compared to cis-MSM, TGW were more likely to be attracted to mostly/only men (aPR: 3.79, 95% CI: 1.57-9.13), have a higher monthly income (aPR: 1.25, 95% CI: 1.04-1.50), have lived in their current residence for <1 year (aPR: 1.21, 95% CI: 1.01-1.46), have engaged in sex work (aPR: 1.48, 95% CI: 1.23-1.77), and be less likely to have ever undergone HIV testing (aPR: 0.83, 95% CI: 0.70-0.98). Among TGW, 149 (42.8%) were taking hormones and 33 (9.5%) had undergone GAS. GAS was more common among TGW who ever used methamphetamines (aOR: 1.55, 95% CI: 1.00-2.41) and those >23 years (18-20-year olds aOR: 0.17, 95% CI: 0.05-0.55; 21-23-year olds aOR: 0.36, 95% CI: 0.20-0.65). Conclusions: TGW and cis-MSM are unique populations; tailored, gender-affirming, differentiated models of HIV prevention and care are necessary to address vulnerabilities specific to each key population.

SARS-CoV-2 Vaccine-Induced Immune Responses Among Hematopoietic Stem Cell Transplant Recipients.

Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), several variables may impact the humoral response among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A retrospective chart review was conducted among SARS-CoV-2-vaccinated HSCT recipients between 2020 and 2022 at a single center in Boston, Massachusetts. Patients age ≥18 years who received doses of Pfizer, Moderna, or J&J vaccines were included. Anti-spike (S) immunoglobulin G (IgG) titer levels were measured using the Roche assay. Responders (≥0.8 U/mL) and nonresponders (<0.8 U/mL) were categorized and analyzed. Multivariable linear and logistic regression were used to estimate the correlation coefficient and odds ratio of response magnitude and status. Results: Of 152 HSCT recipients, 141 (92.8%) were responders, with a median (interquartile range [IQR]) anti-S IgG titer of 2500 (107.9-2500) U/mL at a median (IQR) of 80.5 (36-153.5) days from last dose, regardless of the number of doses received. Higher quantitative titers were associated with receipt of more vaccine doses (coeff, 205.79; 95% CI, 30.10 to 381.47; P = .022), being female (coeff, 343.5; 95% CI, -682.6 to -4.4; P = .047), being younger (<65 years; coeff, 365.2; 95% CI, -711.3 to 19.1; P = .039), and not being on anti-CD20 therapy (coeff, -1163.7; 95% CI, -1717.7 to -609.7; P = .001). Being male (odds ratio [OR], 0.11; 95% CI, 0.01 to 0.93; P = .04) and being on anti-CD20 therapy (OR, 0.16; 95% CI, 0.03 to 0.70; P = .016) were associated with nonresponse. Conclusions: Overall, most HSCT recipients had high SARS-CoV-2 antibody responses. More vaccine doses improved the magnitude of immune responses. Anti-S IgG monitoring may be useful for identifying attenuated vaccine-induced responses.

Early sexual debut is associated with drug use and decreased educational attainment among males and females in Kisumu County, Kenya.

Differing global sociocultural contexts of sexual relationships influence age at first sexual intercourse with potentially long-lasting region-specific effects such as increased risk of contracting HIV and other sexually transmitted infections (STIs). In these cross-sectional analyses of data from the screening and enrollment visits for an HIV incidence study in Kisumu County, Kenya, we evaluated factors associated with having experienced an early sexual debut (ESD) among males and females aged 18-35 years. Clinical evaluation was performed and sexual behaviors were assessed via questionnaire. ESD was defined as self-reported age 15 years or younger at first sexual intercourse. Robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ESD. Of 1057 participants, 542 (51.3%) were female. Participants' median age at study screening was 25 years (interquartile range [IQR]: 22-29), and at sexual debut was 16 years (IQR: 14-17). Five hundred and four participants (47.7%) reported ESD. ESD was less common among females (PR 0.78, CI 0.67-0.90) and participants with more than primary education (PR 0.56, CI 0.47-0.66). ESD was more common in participants with a history of drug use (PR 1.28, CI 1.10-1.49). Drug use removed the protective effect of education (some secondary education or less, no drug use: PR 0.72, CI 0.61-0.85; some secondary education or less, drug use: PR 0.94, CI 0.74-1.18). ESD was common in our study and associated with lower educational attainment and increased likelihood of drug use. Interventions are needed early in life, well before 15 years of age, to encourage engagement in schooling and prevent drug use. Comprehensive sexual education and interventions to prevent drug use may be beneficial before the age of 15 years.

Early sexual debut can be defined as first sexual intercourse at or before 15 years of age. There are many social and cultural factors that influence the age of sexual debut. People who start having sex early in life may exhibit behaviors that increase risk for HIV and other sexually transmitted infections. We conducted a study of men and women aged 18­35 years in Kisumu County, Kenya, which included documentation of medical history, physical examination, laboratory tests, and a questionnaire to assess sexual behaviors. Among the 1057 people studied, the average age of sexual debut was 16.0 years for females and 15.4 years for males. A total of 504 (47.7%) participants reported early sexual debut. The data showed that early sexual debut was less common in females and in participants with more years of education. Early sexual debut was more common in participants with a history of drug use. The findings suggest that interventions to prevent early sexual debut might be improved if they focus on educational attainment and prevention of drug use.

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.

High hepatitis B vaccination coverage among a cohort of predominantly men who have sex with men in Germany.

Incidence of hepatitis B virus (HBV) infection has declined dramatically since the introduction of the HBV vaccine, but gaps remain in coverage. We characterized factors associated with vaccination among individuals with sexual risk of HBV infection. The BRAHMS observational cohort enrolled men and transgender women, without HIV, aged 18-55 years, with behavioral vulnerability to sexually transmitted infections at 10 German outpatient clinics. HBV surface antigen, surface antibody, and core antibody were assessed at screening for cohort eligibility to determine HBV vaccination status. Modified Poisson regression with robust standard errors was used to calculate adjusted prevalence ratios (aPR) and 95% confidence intervals (95% CI) for factors potentially associated with prior HBV vaccination. A total of 1,042 participants were included in these cross-sectional analyses, with 831 participants (79.7%) immune to HBV due to vaccination. Knowledge around HBV vaccination recommendations (aPR: 0.87; 95% CI: 0.78-0.98). and age (aPR 40-49 vs 18-29 years: 0.88; 95% CI: 0.79-0.97) were significantly associated with a history of HBV vaccination in both the unadjusted and adjusted models. Education about the availability of vaccines and recommendations for vaccinations may improve coverage.

Determinants of Preexposure Prophylaxis Cascade Among Sexual and Gender Minorities in Nigeria.

BACKGROUND: Preexposure prophylaxis (PrEP) is effective in preventing human immunodeficiency virus (HIV) infection among sexual and gender minorities (SGMs). We evaluated the characteristics associated with engagement in 7 steps of the PrEP cascade among SGMs in Nigeria. METHODS: Sexual and gender minorities without HIV from the Abuja site of TRUST/RV368 cohort who were surveyed on awareness of and willingness to use PrEP were approached for PrEP initiation upon availability of oral daily PrEP. To understand gaps in the uptake of oral daily PrEP, we categorized the HIV PrEP cascade as (i) education about PrEP, (ii) interest in PrEP, (iii) successful contact, (iv) appointment scheduled, (v) appointment attendance, (vi) PrEP initiation, and (vii) plasma protective levels of tenofovir disoproxil fumarate. Multivariable logistic regression models were used to determine factors associated with each of the 7 steps in the HIV PrEP cascade. RESULTS: Of 788 participants, 718 (91.1%) showed interest in taking oral daily PrEP every day and/or after a sexual act, 542 (68.8%) were successfully contacted, 433 (54.9%) scheduled an appointment, 409 (51.9%) attended a scheduled appointment, 400 (50.8%) initiated oral daily PrEP, and 59 (7.4%) had protective levels of tenofovir disoproxil fumarate. Of initiators of PrEP, 23 (5.8%) seroconverted at a rate of 13.9 cases/100 person-years. Better social support, larger network density, and higher education were associated with engagement in 4 to 5 components of the cascade. CONCLUSIONS: Our data highlight a gap between willingness and actual PrEP use. Despite PrEP's effectiveness in preventing HIV, the optimal impact of PrEP for SGMs in sub-Saharan Africa will require multifaceted approaches that combine social support, education, and destigmatization.

"Building that strong energy": An exploration of stigma coping strategies among sexual and gender minorities in Nigeria.

Sexual and gender minority stigma (SGM stigma) affecting Nigerian sexual and gender minorities (SGM) is associated with suboptimal HIV outcomes, and one mechanism found to explain the relationship is suicidal ideation. A better understanding of coping strategies may help mitigate the harmful impacts of SGM stigma. Interviews of 25 SGM from Abuja, Nigeria participating in the [Blinded for Review] study were thematically analyzed in regards to how they coped with SGM stigma. Four coping themes emerged: avoidant behaviors, self-monitoring so as to not attract stigma, seeking support and safe spaces to be themselves, and empowerment and self-acceptance through a process of cognitive change. They utilized multiple coping strategies, often believing that stigma could be avoided through the right actions and a masculine appearance. Multi-level and person-centered interventions that increase safety and support, facilitate resiliency, and improve mental health and engagement in HIV programming could mitigate the effects of SGM stigma and coping responses of isolation, blame, and mental health stressors among Nigerian SGM.

Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in adults primed with a Japanese encephalitis virus or yellow fever virus vaccine in the USA: a phase 1, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika virus vaccine is, therefore, a global health priority. Assessment of heterologous flavivirus vaccination is important given co-circulation of Japanese encephalitis virus and yellow fever virus with Zika virus. We investigated the effect of priming flavivirus naive participants with a licensed flavivirus vaccine on the safety and immunogenicity of a purified inactivated Zika vaccine (ZPIV). METHODS: This phase 1, placebo-controlled, double-blind trial was done at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, MD, USA. Eligible participants were healthy adults aged 18-49 years, with no detectable evidence of previous flavivirus exposure (by infection or vaccination), as measured by a microneutralisation assay. Individuals with serological evidence of HIV, hepatitis B, or hepatitis C infection were excluded, as were pregnant or breastfeeding women. Participants were recruited sequentially into one of three groups (1:1:1) to receive no primer, two doses of intramuscular Japanese encephalitis virus vaccine (IXIARO), or a single dose of subcutaneous yellow fever virus vaccine (YF-VAX). Within each group, participants were randomly assigned (4:1) to receive intramuscular ZPIV or placebo. Priming vaccinations were given 72-96 days before ZPIV. ZPIV was administered either two or three times, at days 0, 28, and 196-234. The primary outcome was occurrence of solicited systemic and local adverse events along with serious adverse events and adverse events of special interest. These data were analysed in all participants receiving at least one dose of ZPIV or placebo. Secondary outcomes included measurement of neutralizing antibody responses following ZPIV vaccination in all volunteers with available post-vaccination data. This trial is registered at ClinicalTrials.gov, NCT02963909. FINDINGS: Between Nov 7, 2016, and Oct 30, 2018, 134 participants were assessed for eligibility. 21 did not meet inclusion criteria, 29 met exclusion criteria, and ten declined to participate. 75 participants were recruited and randomly assigned. 35 (47%) of 75 participants were male and 40 (53%) were female. 25 (33%) of 75 participants identified as Black or African American and 42 (56%) identified as White. These proportions and other baseline characteristics were similar between groups. There were no statistically significant differences in age, gender, race, or BMI between those who did and did not opt into the third dose. All participants received the planned priming IXIARO and YF-VAX vaccinations, but one participant who received YF-VAX dropped out before receipt of the first dose of ZPIV. 50 participants received a third dose of ZPIV or placebo, including 14 flavivirus-naive people, 17 people primed with Japanese encephalitis virus vaccine, and 19 participants primed with yellow fever vaccine. Vaccinations were well tolerated across groups. Pain at the injection site was the only adverse event reported more frequently in participants who received ZPIV than in those who received placebo (39 [65%] of 60 participants, 95% CI 51·6-76·9 who received ZPIV vs three [21·4%] of 14 who received placebo; 4·7-50·8; p=0·006). No patients had an adverse event of special interest or serious adverse event related to study treatment. At day 57, the flavivirus-naive volunteers had an 88% (63·6-98·5, 15 of 17) seroconversion rate (neutralising antibody titre ≥1:10) and geometric mean neutralising antibody titre (GMT) against Zika virus of 100·8 (39·7-255·7). In the Japanese encephalitis vaccine-primed group, the day 57 seroconversion rate was 31·6% (95% CI 12·6-56·6, six of 19) and GMT was 11·8 (6·1-22·8). Participants primed with YF-VAX had a seroconversion rate of 25% (95% CI 8·7-49·1, five of 20) and GMT of 6·6 (5·2-8·4). Humoral immune responses rose substantially following a third dose of ZPIV, with seroconversion rates of 100% (69·2-100; ten of ten), 92·9% (66·1-99·8; 13 of 14), and 60% (32·2-83·7, nine of 15) and GMTs of 511·5 (177·6-1473·6), 174·2 (51·6-587·6), and 79 (19·0-326·8) in the flavivirus naive, Japanese encephalitis vaccine-primed, and yellow fever vaccine-primed groups, respectively. INTERPRETATION: We found ZPIV to be well tolerated in flavivirus naive and primed adults but that immunogenicity varied significantly according to antecedent flavivirus vaccination status. Immune bias towards the flavivirus antigen of initial exposure and the timing of vaccination may have impacted responses. A third ZPIV dose overcame much, but not all, of the discrepancy in immunogenicity. The results of this phase 1 clinical trial have implications for further evaluation of ZPIV's immunisation schedule and use of concomitant vaccinations. FUNDING: Department of Defense, Defense Health Agency; National Institute of Allergy and Infectious Diseases; and Division of Microbiology and Infectious Disease.

Preparing for future European efficacy trials of interventions to prevent HIV and other sexually transmitted infections: Lessons on willingness to participate and barriers to participation from ten German clinics serving behaviorally vulnerable men who have sex with men.

Future efficacy testing of interventions to prevent HIV or other infections will require engagement of vulnerable populations. We characterized willingness to participate in a future HIV vaccine trial and barriers to participation among men who have sex with men in a 12-month German cohort study. Among 1015 participants at enrollment, 604 (60%) reported willingness, 60 (6%) were unwilling, 351 (35%) were unsure or refused to answer. Among those unwilling, the primary reason was fear of getting HIV. Among those willing, reasons included protection against HIV and furthering scientific knowledge. In a multivariable logistic regression model, higher odds of willingness to participate were seen among participants at the 12-month visit (aOR: 1.09, 95% CI: 1.04-1.15) and with prior knowledge of HIV vaccine research (aOR: 1.14, 95% CI: 1.06-1.23). Educating potential participants about vaccine research may facilitate recruitment and participation in future trials of HIV vaccine candidates and other prevention interventions.