A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings.

BACKGROUND: HIV Vaccine Trials Network 703/HIV Prevention Trials Network 081 is a phase 2b randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of passively infused monoclonal antibody VRC01 in preventing HIV acquisition in heterosexual women between the ages of 18 and 50 years at risk of HIV. Participants were enrolled at 20 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, and Zimbabwe. It is one of the 2 Antibody Mediated Prevention efficacy trials, with HIV Vaccine Trials Network 704/HIV Prevention Trials Network 085, evaluating VRC01 for HIV prevention. METHODS: Intense community engagement was used to optimize participant recruitment and retention. Participants were randomly assigned to receive intravenous VRC01 10 mg/kg, VRC01 30 mg/kg, or placebo in a 1:1:1 ratio. Infusions were given every 8 weeks with a total of 10 infusions and 104 weeks of follow-up after the first infusion. RESULTS: Between May 2016 and September 2018, 1924 women from sub-Saharan Africa were enrolled. The median age was 26 years (interquartile range: 22-30), and 98.9% were Black. Sexually transmitted infection prevalence at enrollment included chlamydia (16.9%), trichomonas (7.2%), gonorrhea (5.7%), and syphilis (2.2%). External condoms (83.2%) and injectable contraceptives (61.1%) were the methods of contraception most frequently used by participants. In total, through April 3, 2020, 38,490 clinic visits were completed with a retention rate of 96% and 16,807 infusions administered with an adherence rate of 98%. CONCLUSIONS: This proof-of-concept, large-scale monoclonal antibody study demonstrates the feasibility of conducting complex trials involving intravenous infusions in high incidence populations in sub-Saharan Africa.

Standardized metrics can reveal region-specific opportunities in community engagement to aid recruitment in HIV prevention trials.

Good Participatory Practice (GPP) guidelines support and direct community engagement practices in biomedical HIV prevention trials, however no standardized metrics define the implementation and evaluation of these practices. Collaboratively, the Community Program staff of the HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN) created a metric to describe, monitor, and evaluate one component of GPP, recruitment practices, in two HIV monoclonal Antibody Mediated Prevention (AMP) clinical trials, HVTN 703/HPTN 081 and HVTN 704/HPTN 085. Through consultation with community representatives from each clinical research site (hereafter "site(s)"), who made up the study Community Working Groups, recruitment strategy descriptors were developed for both trials to characterize responses to "How did you hear about the AMP study?" The Community Working Groups also helped to define and establish time points that were selected to allow comparisons across sites. Data were collected by 43 of 46 clinical research sites from January 1, 2017 to February 28, 2018. All 43 sites used multiple recruitment strategies successfully, but strategies varied by region. Globally, referrals was the most efficient and effective recruitment strategy as evidenced by the screening: enrollment ratio of 2.2:1 in Africa, and 2.1:1 in the Americas/Switzerland. Print materials were also valuable globally (3:1 Africa, 4.2:1 Americas/Switzerland). In Africa, in-person outreach was also quite effective (2.3:1) and led to the most enrollments (748 of 1186, 63%). In the Americas/Switzerland, outreach was also effective (2.6:1), but internet use resulted in the most screens (1893 of 4275, 44%) and enrollments (677 of 1531, 44%), compared to 12 of 2887 (0.4%) and 2 of 1204 (0.1%) in Africa, respectively. Standardized metrics and data collection aid meaningful comparisons of optimal community engagement methods for trial enrollment. Internet strategies had better success in the Americas/Switzerland than in sub-Saharan African countries. Data are essential in outreach staff efforts to improve screening-to-enrollment ratios. Because the effectiveness of recruitment strategies varies by region, it is critical that clinical research sites tailor community engagement and recruitment strategies to their local environment, and that they are supported with resources enabling use of a range of approaches.