Clinical trials testing broadly neutralizing antibody against HIV demonstrate efficacy against sensitive strains

The proof-of-concept AMP studies demonstrated that a broadly neutralizing antibody (bnAb) called VRC01 was effective at preventing the acquisition of HIV strains to the 30% of strains that were sensitive to the bnAb. This finding was seen both in Sub-Saharan Africa and the U.S. and South America. VRCO1 did not prevent the acquisition of HIV to strains that were resistant to the bNAb. As the resistant strains constituted nearly 70% of the circulating strains in these regions, there was no difference noted between the VRC01 arms and placebo arm in terms of overall prevention of HIV acquisition. The sensitivity to bNAbs was assessed by a laboratory test that measures a virus' susceptibility to neutralization by an antibody.

The two studies (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) opened in 2016 and successfully enrolled 4,623 participants. The AMP studies are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The studies are conducted jointly by the HIV Vaccine Trials Network (HVTN) and HIV Prevention Trials Network (HPTN).

The NIAID Vaccine Research Center (VRC) isolated VRC01 in 2010 from the blood of a person living with HIV and subsequently manufactured the antibody for the AMP studies. Data from the AMP studies were first reported at a press conference hosted by the 4th International HIV Research for Prevention Conference (HIVR4P) on January 26, 2021. VRC01 was 75% effective at preventing acquisition of HIV strains that were susceptible to the bnAb (in vitro sensitivity to the antibody had an IC80 of <1 μg/ml) in cisgender men and transgender persons vulnerable to HIV acquisition in South America, Switzerland and the U.S., and in cisgender women vulnerable to HIV acquisition in Sub-Saharan Africa. The AMP data were published today in the New England Journal of Medicine.

Susceptibility to VRC01 of the HIV strain to which a person was exposed was the key determinant of how well the antibody worked to prevent HIV acquisition. Among participants who acquired a VRC01-sensitive HIV strain during the trials, the HIV incidence rate was 0.2 per 100 person-years for VRC01 recipients and 0.86 per 100 person-years for placebo recipients. Results were similar in the HVTN 704/HPTN 085 trial conducted among cisgender men and transgender persons in the U.S., Switzerland and South America (exposed primarily to subtype B variants) and in the HVTN 703/HPTN 081 trial in cisgender women in Sub-Saharan Africa (exposed primarily to subtype C variants).

"The AMP trials were designed to determine whether long-term administration of a bnAb could reduce HIV acquisition, if susceptibility of circulating viruses in the community to the bnAb would influence prevention efficacy, and if measuring this susceptibility would be a biomarker of prevention efficacy. All three of these questions were answered by these two trials," said Larry Corey, M.D., AMP Protocol Chair and Principal Investigator, HVTN Leadership Operations Center, which is based at the Fred Hutchinson Cancer Research Center.

Cisgender men and transgender persons who have sex with cisgender men were enrolled from communities in Brazil, Peru, Switzerland, and the U.S. in HVTN 704/HPTN 085. Cisgender women were enrolled from communities in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, and Zimbabwe in HVTN 703/HPTN 081. The median age of participants enrolled in HVTN 704/HPTN 085 is 28 years, and 31.6% are White, and 15.1% Black, and 57.1% Latinx. In HVTN 703/HPTN 081, the median age of participants is 26 years, and 98.9% are Black. Study participants were randomized to receive intravenous infusions of VRC01 at 10 mg/kg (active lower dose), VRC01 at 30 mg/kg (active higher dose), or placebo administered every eight weeks (total of 10 intravenous infusions). Testing for HIV infection occurred every four weeks, and participants were followed for two years. PrEP use was evenly distributed among the randomized study arms. VRC01 was well-tolerated by participants in both trials, and no safety concerns were identified.

The results indicate that more than one single bnAb is needed to prevent HIV acquisition. Similar to antiretroviral medications, combination monoclonal antibody cocktails need to be developed to offer effective protection against the diverse population of HIV strains that circulate in these communities.

"The results from the AMP trials will be instrumental in the development of future trials testing combinations of the highly potent long-acting bnAbs under clinical development," said Myron Cohen, M.D., AMP Protocol Chair, HPTN Principal Investigator, and Director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill. "We look forward to using this knowledge as we continue towards our goal to end HIV."

There are still more than 1.7 million new cases per year of HIV globally; more than 75 million people have acquired HIV and more than 32 million people have died from AIDS-related illnesses since the pandemic began. The need for a safe and effective preventive HIV vaccine and other HIV prevention technologies is as urgent as ever.