Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

BACKGROUND: A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS: In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS: In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS: The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).

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.

Development of an international sexual and reproductive health survey instrument: results from a pilot WHO/HRP consultative Delphi process.

Population health surveys are rarely comprehensive in addressing sexual health, and population-representative surveys often lack standardised measures for collecting comparable data across countries. We present a sexual health survey instrument and implementation considerations for population-level sexual health research. The brief, comprehensive sexual health survey and consensus statement was developed via a multi-step process (an open call, a hackathon, and a modified Delphi process). The survey items, domains, entire instruments, and implementation considerations to develop a sexual health survey were solicited via a global crowdsourcing open call. The open call received 175 contributions from 49 countries. Following review of submissions from the open call, 18 finalists and eight facilitators with expertise in sexual health research, especially in low- and middle-income countries (LMICs), were invited to a 3-day hackathon to harmonise a survey instrument. Consensus was achieved through an iterative, modified Delphi process that included three rounds of online surveys. The entire process resulted in a 19-item consensus statement and a brief sexual health survey instrument. This is the first global consensus on a sexual and reproductive health survey instrument that can be used to generate cross-national comparative data in both high-income and LMICs. The inclusive process identified priority domains for improvement and can inform the design of sexual and reproductive health programs and contextually relevant data for comparable research across countries.

Self-Identity, Beliefs, and Behavior Among Men Who Have Sex with Transgender Women: Implications for HIV Research and Interventions.

While transgender women have been identified as a global priority population for HIV prevention and treatment, little is known about the cisgender male partners of transgender women, including their sexual behavior and HIV prevalence. Previous research has suggested that these male partners have varied identities and sexual behavior, which make identifying and engaging them in research difficult. This paper describes interviews conducted with fifteen cisgender men who reported recent sexual activity with transgender women in Lima, Peru. The purpose of this research was to explore how these men reported their identities and sexual behavior, to better understand how they would interact with HIV outreach, research, and care. The major themes were sexual orientation and identity; view of transgender partners; social ties to transgender women and other men with transgender women partners; disclosure of relationships; HIV knowledge and risk perception; and attitudes toward interventions. We found that language used to assess sexual orientation was problematic in this population, due to lack of consistency between orientation and reported behavior, and unfamiliarity with terms used to describe sexual orientation. In addition, stigma, lack of knowledge of HIV prevention methods, and fear of disclosure of sexual behavior were identified as barriers that could impact engagement in HIV research, prevention, and care. However, participants reported social relationships with both transgender women and other men who have transgender partners, presenting possible avenues for recruitment into HIV research and healthcare services.

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.

Misclassification of Sex Assigned at Birth in the Behavioral Risk Factor Surveillance System and Transgender Reproductive Health: A Quantitative Bias Analysis.

BACKGROUND: National surveys based on probability sampling methods, such as the Behavioral Risk Factor and Surveillance System (BRFSS), are crucial tools for unbiased estimates of health disparities. In 2014, the BRFSS began offering a module to capture transgender and gender nonconforming identity. Although the BRFSS provides much needed data on the this population, these respondents are vulnerable to misclassification of sex assigned at birth. METHODS: We applied quantitative bias analysis to explore the magnitude and direction of the systematic bias present as a result of this misclassification. We use multivariate Poisson regression with robust standard errors to estimate the association between gender and four sex-specific outcomes: prostate-specific antigen testing, Pap testing, hysterectomy, and pregnancy. We applied single and multiple imputation methods, and probabilistic adjustments to explore bias present in these estimates. RESULTS: Combined BRFSS data from 2014, 2015, and 2016 included 1078 transgender women, 701 transgender men, and 450 gender nonconforming individuals. Sex assigned at birth was misclassified among 29.6% of transgender women and 30.2% of transgender men. Transgender and gender nonconforming individuals excluded due to sex-based skip patterns are demographically distinct from those who were asked reproductive health questions, suggesting that there is noteworthy selection bias present in the data. Estimates for gender nonconforming respondents are vulnerable to small degrees of bias, while estimates for cancer screenings among transgender women and men are more robust to moderate degrees of bias. CONCLUSION: Our results demonstrate that the BRFSS methodology introduces substantial uncertainty into reproductive health measures, which could bias population-based estimates. These findings emphasize the importance of implementing validated sex and gender questions in health surveillance surveys. See video abstract at, http://links.lww.com/EDE/B562.

Moderating Factors in an Anti-stigma Intervention for African American Women with HIV in the United States: A Secondary Analysis of the UNITY Trial.

African American women experience higher rates of HIV than other women in the United States, and stigma has been identified as an important determinant of engagement in HIV care. Our study examined whether key variables moderated the effect of an anti-stigma intervention on outcomes among African American women receiving treatment for HIV. Twelve potential moderators included: age, years lived with HIV, marital status, employment status, education level, PTSD diagnosis, alcohol use, social support, baseline CD4 count, baseline viral load, and number of children. Outcomes included changes in: HIV-related stigma, social support, depressive symptoms, PTSD symptoms, alcohol use, viral load, and engagement in HIV care. Results suggest that the intervention is associated with greater improvement in engagement in care among participants with PTSD or depression at baseline, and may help maintain engagement in care among participants experiencing certain mental health conditions. This provides opportunities to address discriminatory structural barriers that lead to stigma and drop-offs in HIV care.

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.

Mobile Phone Questionnaires for Sexual Risk Data Collection Among Young Women in Soweto, South Africa.

Recall and social desirability bias undermine self-report of paper-and-pencil questionnaires. Mobile phone questionnaires may overcome these challenges. We assessed and compared sexual risk behavior reporting via in-clinic paper-and-pencil and mobile phone questionnaires. HVTN 915 was a prospective cohort study of 50 adult women in Soweto, who completed daily mobile phone, and eight interviewer-administered in-clinic questionnaires over 12 weeks to assess sexual risk. Daily mobile phone response rates were 82% (n = 3486/4500); 45% (n = 1565/3486) reported vaginal sex (median sex acts 2 (IQR: 1-3)) within 24 h and 40% (n = 618/1565) consistent condom. Vaginal sex reporting was significantly higher via mobile phone across all visits (p < 0.0001). There was no significant difference in condom use reporting by mobile phone and in-clinic paper-based questionnaires across all visits (p = 0.5134). The results show high adherence and reporting of sex on the mobile phone questionnaire. We demonstrate feasibility in collecting mobile phone sexual risk data.

Fertility desires and preferences for safer conception strategies among people receiving care for HIV at a publicly-funded clinic in Seattle, WA.

Understanding fertility desires and preferences for HIV prevention among individuals living with HIV, including the potential use of pre-exposure prophylaxis (PrEP) by HIV uninfected partners, can inform the delivery of safer conception counseling to reduce the risk of HIV transmission during pregnancy attempts. Men and women, predominantly heterosexual, engaged in HIV care in Seattle, WA, self-administered a questionnaire and we abstracted antiretroviral therapy (ART) status and HIV viral levels from medical records. We summarized participants' sexual behavior, fertility desires, and preferences for safer conception strategies and used log-binomial regression to identify demographic, sexual, and behavioral factors associated with perceived acceptability of PrEP for HIV uninfected partners during pregnancy attempts. 52% of the 150 participants were female and the mean age was 48 years (range 23-74). 94.7% of participants were using ART and 79.3% had HIV viral load < 40 copies/mL. 22.2% of men and 34.6% of women reported that a healthcare provider had initiated discussion about fertility desires. 28.7% of participants were reproductive-age and desired children. Among sexually active reproductive-age participants with fertility desires, 56.3% reported inconsistent condom use and 62.5% did not report using effective birth control. 74.4% of reproductive age participants with fertility desires perceived that PrEP would be acceptable to an HIV uninfected partner and there were no significant predictors of PrEP acceptability. Nearly one third of reproductive-aged individuals living with HIV expressed fertility desires, highlighting a need for safer conception counseling in this setting. PrEP and ART were favored safer conception strategies.

Risk and protective factors of posttraumatic stress disorder among African American women living with HIV.

We sought to examine risk and protective factors for Posttraumatic Stress Disorder (PTSD) among African American women living with HIV. This is a cross-sectional analysis of baseline data from a randomized trial of an HIV stigma reduction intervention. We examined data from two-hundred and thirty-nine African American women living with HIV. We examined whether age, marital status, level of education, internalized HIV-related stigma, and social support as potential protective and risk factors for PTSD symptoms using logistic regression. We analyzed bi-variate associations between each variable and PTSD symptoms, and constructed a multivariate logistic regression model adjusting for all variables. We found 67% reported clinically significant PTSD symptoms at baseline. Our results suggest that age, education, and internalized stigma were found to be associated with PTSD symptoms (p < 0.001), with older age and more education as protective factors and stigma as a risk factor for PTSD. Therefore, understanding this relationship may help improve assessment and treatment through evidence- based and trauma-informed strategies.

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.

Mixed-Methods Evaluation of a Novel, Structured, Community-Based Support and Education Intervention for Individuals with HIV/AIDS in KwaZulu-Natal, South Africa.

People living with HIV in Sub-Saharan Africa face significant challenges accessing care. Community-based peer support groups can increase linkage to treatment, though the effectiveness of structured, scalable groups has not been demonstrated. This study aimed to measure the impact of the structured Integrated Access to Care and Treatment intervention on clients' knowledge, attitudes, and practice regarding HIV/AIDS, including their experiences of stigma, in KwaZulu-Natal, South Africa. Data collection involved pre-/post-tests and client interviews. Pre-/post-test data from 66 clients were collected. 17 participants were interviewed. Paired t-tests did not detect significant changes in the main outcomes. Qualitative results suggested a psychosocial benefit as participants connected with their peers, expressed themselves openly, and re-engaged with their communities. Unfortunately, this study did not quantitatively measure psychosocial changes, and the results have limited generalizability to men. I ACT may be an effective complement to clinic-based support services, though further study should quantify the psychosocial benefit.

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.