An investigational anti-HIV antibody delivered intravenously once every eight weeks safely and effectively prevented acquisition of HIV strains sensitive to that antibody, but it did not significantly reduce overall HIV acquisition after 80 weeks among participants in two multinational clinical trials, according to a news release from the National Institutes of Health (NIH).
Known as the Antibody-Mediated Prevention (AMP) Studies, the Phase 2b trials are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. The studies are being conducted jointly by the HIV Vaccine Trials Network (HVTN) and HIV Prevention Trials Network (HPTN).
Broadly neutralizing antibodies (bNAbs), which arise naturally in some people living with HIV and can stop a wide range of HIV strains from infecting human cells in the laboratory, are considered promising candidates for long-acting HIV prevention. These antibodies could be given directly by either infusion or injection or could be elicited by an HIV vaccine.
Launched in 2016, the AMP studies aimed aimed to establish whether infusions of a bNAb called VRC01 are safe, tolerable and effective at preventing HIV acquisition. The NIAID Vaccine Research Center (VRC) discovered VRC01 in 2010 in the blood of a person living with HIV and subsequently manufactured the antibody for the AMP Studies. The two trials included more than 4,600 participants. Men and transgender people who have sex with men were enrolled in the Americas and Europe – geographic regions where HIV subtype B predominates. Women were enrolled in sub-Saharan Africa, where HIV subtype C is dominant.
Study participants were randomly assigned to receive 10 intravenous infusions over 80 weeks of either VRC01 at a dose of 30 milligrams per kilogram of body weight (mg/kg), VRC01 at a dose of 10 mg/kg, or a placebo. Neither the participants nor the study investigators knew who received the antibody or the placebo.
Both VRC01 doses prevented acquisition of HIV strains determined to be sensitive to the bNAb by a laboratory test that measures viral susceptibility to neutralization by an antibody. VRC01 was 75 percent effective at preventing acquisition of sensitive HIV strains across the 80-week study period in both women in sub-Saharan Africa exposed primarily to subtype C variants and men and transgender people in the Americas and Europe exposed primarily to subtype B variants.
Overall, VRC01 infusions did not provide statistically significant protection against HIV acquisition at 80 weeks compared to placebo. Investigators attribute this to the finding that only 30 percent of HIV strains circulating in the regions where the trials were conducted were sensitive to VRC01. Similar to observations with first-generation antiretroviral drugs to treat HIV, resistance to VRC01 exhibited by a majority of HIV strains resulted in the inability of this single bNAb to prevent HIV acquisition over time across the entire study population.
Since the AMP Studies began, scientists have made progress in optimizing known HIV bNAbs in the laboratory to increase the number of HIV strains the antibody can block, how long the antibody lasts in the body, the strength of antibody binding to the virus, and how efficiently the antibody triggers the immune system to attack both the virus and HIV-infected cells. Potentially, these optimized bNAbs could be combined to develop a highly effective HIV prevention method.
