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.

Abstract

BACKGROUND\nHIV Vaccine Trials Network (HVTN) 703/HIV Prevention Trials Network (HPTN) 081 is a phase 2b randomized, double-blind placebo-controlled trial to assess the safety and efficacy of passively infused monoclonal antibody (mAb) VRC01 in preventing HIV acquisition in heterosexual women between the ages of 18 and 50 at risk of HIV. Participants were enrolled at 20 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe. It is one of two Antibody Mediated Prevention (AMP) efficacy trials, with HVTN 704/HPTN 085, evaluating VRC01 for HIV prevention.\n\n\nMETHODS\nIntense community engagement was utilized to optimize participant recruitment and retention. Participants were randomly assigned to receive intravenous (IV) VRC01 10 mg/kg, VRC01 30 mg/kg, or placebo in a 1:1:1 ratio. Infusions were given every eight weeks with a total of 10 infusions and 104 weeks of follow-up after the first infusion.\n\n\nRESULTS\nBetween May 2016 and September 2018, 1924 women from sub-Saharan Africa were enrolled. The median age was 26 (IQR: 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%.\n\n\nCONCLUSIONS\nThis proof-of-concept, large-scale mAb study demonstrates the feasibility of conducting complex trials involving IV infusions in high-incidence populations in sub-Saharan Africa.