Risk Factors Associated with HIV Acquisition in Males Participating in HIV Vaccine Efficacy Trials in South Africa.

In South Africa, HIV acquisition risk has been studied less in people assigned male at birth. We studied the associations between risk behaviors, clinical features and HIV incidence amongst males in two South African HIV preventive vaccine efficacy trials. We used Cox proportional hazards models to test for associations between demographics, sexual behaviors, clinical variables and HIV acquisition among males followed in the HVTN 503 (n = 219) and HVTN 702 (n = 1611) trials. Most males reported no male sexual partners (99.09% in HVTN 503) or identified as heterosexual (88.08% in HVTN 702). Annual HIV incidence was 1.39% in HVTN 503 (95% CI 0.76-2.32%) and 1.33% in HVTN 702 (95% CI 0.80-2.07%). Increased HIV acquisition was significantly associated with anal sex (HR 6.32, 95% CI 3.44-11.62), transactional sex (HR 3.42, 95% CI 1.80-6.50), and non-heterosexual identity (HR 16.23, 95%CI 8.13-32.41) in univariate analyses and non-heterosexual identity (HR 14.99, 95% CI 4.99-45.04; p < 0.01) in multivariate analysis. It is appropriate that prevention efforts in South Africa, although focused on the severe epidemic in young women, also encompass key male populations, including men who have sex with men, but also men who engage in anal or transactional sex.

A qualitative study of stakeholder and researcher perspectives of community engagement practices for HIV vaccine clinical trials in South Africa.

Community engagement increases community trust of research and improves trial participation. However, there is limited documented appraisal of community engagement practices. Several HIV vaccine efficacy trials have been conducted in South Africa, the country most affected by HIV, predominantly in collaboration with the HIV Vaccine Trials Network (HVTN). We explored stakeholder and researcher perspectives of the HVTN community engagement practices used in the Gauteng province of South Africa. In 2017, we conducted a qualitative study. Using semi-structured interview guides, we facilitated two group discussions with Community Advisory Board (CAB) members (n = 13), and 14 in-depth interviews with HVTN-affiliated employees (n = 8 in South Africa and n = 6 in the USA). Group discussions and in-depth interviews were audio-recorded, transcribed verbatim, translated into English, and coded using NVIVO 12 Plus software for thematic data analysis. Overall, median age of study participants was 22 (interquartile range 32-54) years, and 74% (n = 20) were female. Three main themes about community engagement emerged: (i) community engagement as an ongoing iterative relationship between researchers and community; (ii) methods of community engagement, encompassing community education by linking with external stakeholders and through awareness campaigns by pamphlet distribution and mass events, working with communities to develop recruitment messages, and working with CAB as a link to communities; and (iii) strategies to improve community engagement, for example, using simple language, linking with religious leaders and traditional healers, and communicating via conventional (newspapers, television, and radio) and social (videos and listicles) media. Our data indicate ways for researchers to improve relationships with community by understanding local needs, strengthening collaborations, and tailoring communication strategies. In this regard, CABs signify critical linkages between researchers and communities. CABs can relay relevant health research needs, advise on the creation of suitable materials, and link researchers more effectively with community leaders and media.

Willingness to use HIV prevention methods among vaccine efficacy trial participants in Soweto, South Africa: discretion is important.

BACKGROUND: Despite multiple available HIV prevention methods, the HIV epidemic continues to affect South Africa the most. We sought to understand willingness to use actual and hypothetical HIV prevention methods among participants enrolled in a preventative HIV vaccine efficacy trial in Soweto, South Africa. METHODS: We conducted a qualitative study with 38 self-reporting HIV-uninfected and consenting 18-35 year olds participating in the HVTN 702 vaccine efficacy trial in Soweto. Using a semi-structured interview guide, five focus group discussions (FGDs) were held, stratified by age, gender and sexual orientation. The FGDs were composed of: (i) 10 heterosexual women aged 18-24 years; (ii) 9 heterosexual and bisexual women aged 25-35 years; (iii & iv) heterosexual men aged 25-35 years with 7 in both groups; and (v) 5 men aged 18-35 years who have sex with men. FGDs were audio-recorded, transcribed verbatim, translated into English and analysed using thematic analysis. RESULTS: We present five main themes: (i) long-lasting methods are preferable; (ii) condoms are well-known but not preferred for use; (iii) administration route of HIV prevention method is a consideration for the user; (iv) ideal HIV prevention methods should blend into the lifestyle of the user; and the perception that (v) visible prevention methods indicate sexual indiscretion. CONCLUSIONS: The participants' candour about barriers to condom and daily oral pre-exposure prophylaxis (PrEP) use, and expressed preferences for long-lasting, discreet, lifestyle-friendly methods reveal a gap in the biomedical prevention market aiming to reduce sexually acquired HIV in South Africa. Product developers should consider long-acting injectable formulations, such as vaccines, passive antibodies and chemoprophylaxis, for HIV prevention technologies. Future innovations in HIV prevention products may need to address the desire for the method to blend easily into lifestyles, such as food-medication formulations.

What's PrEP?: peer navigator acceptability among minority MSM in Washington.

BACKGROUND: Peer navigation is a promising strategy to link at-risk minority men who have sex with men (MSM) to HIV prevention services including pre-exposure prophylaxis (PrEP). METHODS: Thirty-two Black and 63 Latinx HIV-negative MSM living in western Washington completed a survey examining attitudes towards peer navigation and PrEP. Factor analysis derived a score for peer navigator acceptability, and linear regression identified associations with this outcome. RESULTS: Forty-eight percent were interested in peer navigation. Being insured, higher sexual stigma, and higher PHQ-9 score were associated with higher acceptability, while higher income and having a regular medical provider were associated with lower acceptability. In multivariable analysis, higher sexual stigma predicted higher acceptability, while higher income predicted lower acceptability. Men preferred that peers be matched on sexual orientation, race, age and culture. CONCLUSION: Peer navigation interventions to reach minority men should address stigma, focus on lower-income men, and try to match peers to clients to the extent possible.

'I make sure my doctor doesn't know that I use meth': perceived barriers to pre-exposure prophylaxis (PrEP) uptake among community peer educators in Seattle (WA, USA).

Background HIV disproportionately affects cisgender men and transgender people who have sex with men (MSM/TG) and use methamphetamine. Pre-exposure prophylaxis (PrEP) uptake has been slow in this group. It is important to understand perceptions about PrEP and barriers to its use among MSM/TG who use methamphetamine to reduce new HIV infections. METHODS: We conducted four focus groups with peer educators of a harm reduction program. We assessed their perspectives of PrEP and barriers across the PrEP continuum among MSM/TG who use methamphetamine. RESULTS: Notably, stigma related to the multiple marginalised identities of MSM/TG who use methamphetamine (e.g. MSM/TG-related stigma, methamphetamine-related stigma) was a barrier at each step. We developed a framework that combined the PrEP continuum and a stigma-based treatment cascade to explore these themes and describe the effects of stigma on PrEP engagement. Methamphetamine-related barriers were also identified. CONCLUSIONS: The findings of this study emphasise the importance of incorporating stigma reduction into PrEP delivery for MSM/TG who use methamphetamine.

HIV-Related Stigma and Viral Suppression Among African-American Women: Exploring the Mediating Roles of Depression and ART Nonadherence.

We used baseline data from a sample of African-American women living with HIV who were recruited to participate in a stigma-reduction intervention in Chicago and Birmingham (2013-2015) to (1) evaluate the relationship between HIV-related stigma and viral suppression, and (2) assess the role of depression and nonadherence to antiretroviral therapy (ART) as mediators. Data from women were included in this secondary analysis if they were on ART, had viral load data collected within 8-weeks of study entry and had complete covariate data. We used logistic regression to estimate the total effect of HIV-related stigma (14-item Stigma Scale for Chronic Illness) on viral suppression (< 200 copies/mL), and serial mediation analysis to estimate indirect effects mediated by depressive symptoms (8-item Patient Health Questionnaire) and ART nonadherence (number of days with missed doses). Among 100 women who met study inclusion criteria, 95% reported some level of HIV-related stigma. In adjusted models, higher levels of HIV-related stigma were associated with lower odds of being virally suppressed (AOR = 0.93, 95% CI = 0.89-0.98). In mediation analysis, indirect effects through depression and ART nonadherence were not significant. Findings suggest that HIV-related stigma is common among African-American women living with HIV, and those who experience higher levels of stigma are less likely to be virally suppressed. However, the mechanisms remain unclear.

Development of a targeted educational intervention to increase pre-exposure prophylaxis uptake among cisgender men and transgender individuals who have sex with men and use methamphetamine in Seattle (WA, USA).

Background Cisgender men and transgender individuals who have sex with men (MSM/TG) and use methamphetamine are at elevated risk for HIV and have had limited pre-exposure prophylaxis (PrEP) uptake. The aim of this study was to quantify the knowledge and use of PrEP, identify barriers to PrEP use, and develop a targeted educational campaign to promote PrEP among MSM/TG who use methamphetamine. METHODS: We conducted three consultations with peer educators of Project Needle and Sex Education Outreach Network (NEON) to develop and disseminate educational materials. We surveyed the peers' HIV-negative contacts before and after this work to explore knowledge and opinions about PrEP and to assess the effect of our materials. RESULTS: There were 221 respondents at baseline (August 2016) and 100 at follow-up (April-May 2017). At baseline, nearly all participants had 'heard of PrEP' (96%) and were insured (97%). However, only 3% had ever used PrEP. Peers suggested educational cards that included a definition of PrEP, adherence tips and that PrEP does not prevent other sexually transmissible infections. Peers distributed approximately 2560 educational cards. At follow-up, approximately half the respondents (53%) had seen the cards, and those who did reported significantly more agreement with the majority of the card messages about PrEP. Significantly more participants reported ever receiving PrEP at follow-up (21%; P<0.001). There was a trend between seeing the cards and PrEP use (P=0.053). CONCLUSIONS: Although we cannot be certain that the effect was due to our intervention, a greater number of the peers' contacts reported receiving PrEP at follow-up, and those who saw our materials were more likely to agree with factual statements about PrEP. There is continued need for PrEP education for MSM/TG who use methamphetamine.

Partner Abuse Among HIV-Positive Sexual Minority Men: "That Was All I Deserved . . ."

Living with HIV can be both a precipitant and a consequence of partner abuse (PA) across populations, including male-male partnerships. However, overlapping experiences of living with HIV and experiencing PA are not well characterized. We conducted 24 qualitative interviews with urban HIV-positive sexual minority men (SMM) recruited from a public hospital HIV clinic in Seattle, Washington, who reported lifetime PA histories, and analyzed them using content analysis. Participants reported psychological, physical, and sexual victimization from partners, varying in severity. Themes included (a) how HIV and minority stress (e.g., through self-stigma, serosorting) and (b) familial and repeated exposure to violence (e.g., through normalization or acceptance of PA, partnering as strategy for increasing one's own safety, esteem, or social status), independently and in combination, provided a context for the men's victimization. Our findings suggest that PA-related interventions might focus on coping with stigma, expanding social networks, and educating SMM about dysfunctional relationship dynamics.

Enhancing diversity in the public health research workforce: the research and mentorship program for future HIV vaccine scientists.

OBJECTIVES: We developed and evaluated a novel National Institutes of Health-sponsored Research and Mentorship Program for African American and Hispanic medical students embedded within the international, multisite HIV Vaccine Trials Network, and explored its impact on scientific knowledge, acquired skills, and future career plans. METHODS: Scholars conducted social, behavioral, clinical, or laboratory-based research projects with HIV Vaccine Trials Network investigators over 8 to 16 weeks (track 1) or 9 to 12 months (track 2). We conducted an in-depth, mixed-methods evaluation of the first 2 cohorts (2011-2013) to identify program strengths, areas for improvement, and influence on professional development. RESULTS: A pre-post program assessment demonstrated increases in self-reported knowledge, professional skills, and interest in future HIV vaccine research. During in-depth interviews, scholars reported that a supportive, centrally administered program; available funding; and highly involved mentors and staff were keys to the program's early success. CONCLUSIONS: A multicomponent, mentored research experience that engages medical students from underrepresented communities and is organized within a clinical trials network may expand the pool of diverse public health scientists. Efforts to sustain scholar interest over time and track career trajectories are warranted.

Sexual victimization, alcohol intoxication, sexual-emotional responding, and sexual risk in heavy episodic drinking women.

This study used an experimental paradigm to investigate the roles of sexual victimization history and alcohol intoxication in young women's sexual-emotional responding and sexual risk taking. A nonclinical community sample of 436 young women, with both an instance of heavy episodic drinking and some HIV/STI risk exposure in the past year, completed childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) measures. A majority of them reported CSA and/or ASA, including rape and attempted rape. After random assignment to a high alcohol dose (.10 %) or control condition, participants read and projected themselves into an eroticized scenario of a sexual encounter involving a new partner. As the story protagonist, each participant rated her positive mood and her sexual arousal, sensation, and desire, and then indicated her likelihood of engaging in unprotected sex. Structural equation modeling analyses revealed that ASA and alcohol were directly associated with heightened risk taking, and alcohol's effects were partially mediated by positive mood and sexual desire. ASA was associated with attenuated sexual-emotional responding and resulted in diminished risk taking via this suppression. These are the first findings indicating that, compared to non-victimized counterparts, sexually victimized women respond differently in alcohol-involved sexual encounters in terms of sexual-emotional responding and risk-taking intentions. Implications include assessing victimization history and drinking among women seeking treatment for either concern, particularly women at risk for HIV, and alerting them to ways their histories and behavior may combine to exacerbate their sexual risks.

Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial.

In the PREVENT-19 phase 3 trial of the NVX-CoV2373 vaccine (NCT04611802), anti-spike binding IgG concentration (spike IgG), anti-RBD binding IgG concentration (RBD IgG), and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks post-dose two are assessed as correlates of risk and as correlates of protection against COVID-19. Analyses are conducted in the U.S. cohort of baseline SARS-CoV-2 negative per-protocol participants using a case-cohort design that measures the markers from all 12 vaccine recipient breakthrough COVID-19 cases starting 7 days post antibody measurement and from 639 vaccine recipient non-cases. All markers are inversely associated with COVID-19 risk and directly associated with vaccine efficacy. In vaccine recipients with nAb ID50 titers of 50, 100, and 7230 international units (IU50)/ml, vaccine efficacy estimates are 75.7% (49.8%, 93.2%), 81.7% (66.3%, 93.2%), and 96.8% (88.3%, 99.3%). The results support potential cross-vaccine platform applications of these markers for guiding decisions about vaccine approval and use.

Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine.

In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was -5.8% (-651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines.

Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial.

The best assay or marker to define mRNA-1273 vaccine-induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antibodies to the spike protein (spike IgG) or receptor binding domain (RBD IgG) and pseudovirus neutralizing antibody 50 or 80% inhibitory dilution titer measured on day 29 or day 57, as correlates of risk (CoRs) and CoPs against symptomatic COVID-19 over 4 months after dose. Here, we assessed a new marker, live virus 50% microneutralization titer (LV-MN50), and compared and combined markers in multivariable analyses. LV-MN50 was an inverse CoR, with a hazard ratio of 0.39 (95% confidence interval, 0.19 to 0.83) at day 29 and 0.51 (95% confidence interval, 0.25 to 1.04) at day 57 per 10-fold increase. In multivariable analyses, pseudovirus neutralization titers and anti-spike binding antibodies performed best as CoRs; combining antibody markers did not improve correlates. Pseudovirus neutralization titer was the strongest independent correlate in a multivariable model. Overall, these results supported pseudovirus neutralizing and binding antibody assays as CoRs and CoPs, with the live virus assay as a weaker correlate in this sample set. Day 29 markers performed as well as day 57 markers as CoPs, which could accelerate immunogenicity and immunobridging studies.

Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial.

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs.

Awakening: The Unveiling of Historically Unaddressed Social Inequities During the COVID-19 Pandemic in the United States.

The violence and victimization brought by colonization and slavery and justified for over a century by race-based science have resulted in enduring inequities for black, Indigenous and people of color (BIPOC) across the United States. This is particularly true if BIPOC individuals have other intersecting devalued identities. We highlight how such longstanding inequities paved the way for the disproportionate burdens of coronavirus disease 2019 (COVID-19) among the BIPOC populations across the country and provide recommendations on how to improve COVID-19 mitigation strategies with the goal of eliminating disparities.

Perceptions of Sexual Risk, PrEP Services, and Peer Navigation Support among HIV-Negative Latinx and Black Men who have Sex with Men (MSM) Residing in Western Washington.

Introduction: HIV PrEP (pre-exposure prophylaxis) is underutilized among Latinx and Black men who have sex with men (MSM) in the United States. Although peer navigation approaches may increase PrEP uptake and adherence, it remains unclear what strategies work best for MSM of color. Methods: From July 2017 to August 2018, we conducted semi-structured in-depth interviews with 25 purposively sampled Latinx and Black cisgender MSM to evaluate how the intersectionality of race/ethnicity, sexual orientation, and other identities influenced men's views on PrEP in general and on peer navigation specifically. Thematic analysis was used to identify and analyze emergent themes. Results: Emergent themes included: (1) awareness of vulnerability in intimate relationships; (2) barriers to PrEP initiation including perceived side effects, stigma, and financial concerns; (3) a wish to connect with other Latinx and Black MSM in a health and prevention space; and (4) the desire for peer matching based on identity considerations and lived experience. Younger men and Spanish-speaking Latinx men were most interested in peer navigation to access PrEP, while bisexual men had confidentiality concerns. Conclusions: In our study, Latinx and Black MSM viewed peer navigation services favorably, especially if they addressed men's desire to connect with other MSM of color. Policy Implications: Developing culturally-congruent peer navigation programming could help improve PrEP uptake and care engagement for Latinx and Black MSM. Programs should recruit peers from the racial/ethnic minority communities most impacted by HIV and prioritize matching peers to clients based on identity concerns, needs, and preferences.

Immune Correlates Analysis of a Single Ad26.COV2.S Dose in the ENSEMBLE COVID-19 Vaccine Efficacy Clinical Trial.

Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.

Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.

In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.