Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody

Abstract

the HVTN 704/HPTN 085 study group Background: The Antibody-Mediated Prevention trials (HVTN 704/ HPTN 085 and HVTN 703/HPTN 081) are the first efficacy trials to evaluate whether VRC01, a broadly neutralizing monoclonal antibody targeting the CD4-binding site of the HIV envelope protein, prevents sexual transmission of HIV-1. HVTN 704/HPTN 085 enrolled 2701 cisgender men and transgender (TG) individuals who have sex with men at 26 sites in Brazil, Peru, Switzerland, and the United States.Methods: Participants were recruited and retained through early, extensive community engagement. Eligible participants were randomized 1:1:1 to 10 mg/kg or 30 mg/kg of VRC01 or saline placebo. Visits occurred monthly, with intravenous (IV) infusions every 8 weeks over 2 years, for a total of 10 infusions. Participants were followed for 104 weeks after first infusion. Results:The median HVTN 704/HPTN 085 participant age was 28 years; 99% were assigned male sex; 90% identified as cisgender men, 5% as TG women and the remaining as other genders. Thirtytwo percent were White, 15% Black, and 57% Hispanic/Latinx. Twenty-eight percent had a sexually transmitted infection at enrollment. More than 23,000 infusions were administered with no serious IV administration complications. Overall, retention and adherence to the study schedule exceeded 90%, and the dropout rate was below 10% annually (7.3 per 100 person-years) through week 80, the last visit for the primary end point.Conclusions: HVTN 704/HPTN 085 exceeded accrual and retention expectations. With exceptional safety of IV administration and operational feasibility, it paves the way for future large-scale monoclonal antibody trials for HIV prevention and/or treatment.

Broadly Neutralizing Antibodies for HIV-1 Prevention

“…The NIAID-funded HIV Vaccine Trials Network (HVTN) and HIV Prevention Trials Network (HPTN) therefore collaborated on the design and conduct of the two Antibody Mediated Prevention (AMP) trials, HVTN 704/HPTN 085 (NCT02716675) and HVTN 703/HPTN 081 (NCT02568215) ( 107 ). HVTN 704/HPTN 085 enrolled 2,699 cisgender men and transgender (TG) people who have sex with men in Brazil, Peru, Switzerland, and the US ( 108 ) while HVTN 703/HPTN 081 enrolled 1,924 cisgender women in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, and Zimbabwe ( 109 ).…”

Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS

“…Recent studies have shown that passively infused broadly neutralizing monoclonal antibodies (bnAbs) exhibit favorable safety profiles and are promising strategies for therapy and prevention of HIV-1 (5)(6)(7). The Antibody Mediated Prevention (AMP) studies substantiated the concept that a bnAb can prevent HIV acquisition (5,(8)(9)(10). In addition to prevention of HIV-1 infection, bnAbs are being investigated as an approach to achieve viral control without the use of antiretroviral therapy (11)(12)(13).…”

Combinations of Single Chain Variable Fragments From HIV Broadly Neutralizing Antibodies Demonstrate High Potency and Breadth

“…The results of the first efficacy trials of an antibody for HIV prevention tested in Africa and the Americas have recently been published (14)(15)(16)(17). These two Antibody-Mediated Prevention (AMP www.ampstudy.org.za) trials showed that VRC01 had 75% prevention efficacy in high-risk men and women if the infecting virus was sensitive to the antibody at <1mg/ml (IC 80 ).…”