Most advanced 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 that were sensitive to the bnAb. This 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 April 2016 and successfully enrolled 4,623 participants. The Desmond Tutu Health Foundation’s clinical research site at Groote Schuur Hospital was a participating site in the trial, where it enrolled women (aged 19-40) who were at a high risk of HIV infection.
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).
Prof Linda-Gail Bekker, COO of the Desmond Tutu Health Foundation, says that the promising results provide hope for the future of HIV prevention research. “AMP gives a green light to developing these amazing broadly neutralising antibodies for use to prevent HIV in a variety of settings. More prevention choices will enable better use”, said Bekker.
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 reported yesterday at a press conference hosted by the 4th International HIV Research for Prevention Conference (HIVR4P). 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 women vulnerable to HIV acquisition in sub-Saharan Africa, and in men and transgender persons vulnerable to HIV acquisition in South America, Switzerland and the United States.
However, intravenous administration of VRC01 at eight-week intervals over 20 months did not significantly reduce HIV transmission overall in either trial. Investigators found that only 30% of the HIV strains circulating in the regions where the trials were conducted were sensitive to VRC01. VRC01 did not prevent acquisition of resistant HIV strains (in vitro sensitivity to the antibody had an IC80 of >1 µg/ml), which were able to escape neutralization by the antibody and cause infection. Similar to what was observed with first-generation antiretroviral drugs such as AZT to treat HIV, resistance to VRC01 exhibited by a majority of circulating HIV strains resulted in the inability of this single bnAb to prevent HIV acquisition over time in the two study populations.
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 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 women in sub-Saharan Africa (exposed primarily to subtype C variants).
“The results of these trials have answered many important questions about prevention efficacy and will be instrumental in the development of future long-acting prevention methods”, said Prof Catherine Orrell, the AMP Principal Investigator at the DTHF’s Groote Schuur Hospital site. “We could not have done it without the support of our local communities. Our deepest thanks go to the superb group of young women who participated in this ground-breaking research.”
Men and transgender persons who have sex with men were enrolled from communities in Brazil, Peru, Switzerland, and the United States in HVTN 704/HPTN 085. Women were enrolled from communities in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, and Zimbabwe in HVTN 703/HPTN 081.
It is estimated that 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.