According to a small research published today in the journal Nature, HIV patients who started antiretroviral medication (ART) early in their illness experienced a long duration of HIV suppression without ART after obtaining two broadly neutralizing anti-HIV antibodies (bNAbs).
According to the findings, combined bNAb treatment might be a potential option to daily ART for HIV patients. Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health, collaborated on the study with researchers from the NIH Clinical Center, the Maple Leaf Medical Clinic in Toronto, the Frederick National Laboratory for Cancer Research, Harvard Medical School in Boston, and The Rockefeller University in New York City.
Despite the fact that oral antiretrovirals are very successful in keeping HIV levels under control, some HIV patients find it difficult to stick to a daily drug schedule. Furthermore, the drugs may cause long-term negative effects as a result of long-term use, as well as the development of drug-resistant viruses.
Single bNAbs had limited efficacy in maintaining virus levels low in prior studies, in part because bNAb-resistant HIV was already present or had arisen in the individual.
To address this issue, researchers at the National Institute of Allergy and Infectious Diseases’ Laboratory of Immunoregulation tried a dual combination of bNAbs named 3BNC117 and 10-1074 that target separate areas of the HIV surface.
Between September 2018 and January 2021, the researchers conducted a two-part clinical experiment. The first component was a 14-person HIV-positive Phase 1 randomized, placebo-controlled experiment. These people had begun antiretroviral therapy (ART) at the early stages of HIV infection.
Shortly after receiving their initial infusion of the combination bNAbs or placebo, they were weaned off antiretrovirals. Participants received up to eight bNAb or placebo injections over the course of 24 weeks, two in the first month and once a month thereafter. Every two weeks, HIV levels and CD4 T-cell counts were checked.
The goal of the trial was to explore if bNAb medication could suppress HIV in the absence of antiretroviral therapy (ART). Compared to six of the seven people who received placebo, none of the seven who received the bNAb therapy had to restart ART before 28 weeks post-infusion.
The median time off antiretrovirals was 39.6 weeks in the bNAb group and 9.4 weeks in the placebo group.
The trial’s second component involved bNAb infusions in a group of five study participants who were not on ART but still had low HIV levels. Only two of the five trial participants sustained complete viral suppression for an average of 41.7 weeks after receiving bNAb infusions in this smaller cohort.
The authors point out that if patients had virus resistant to either or both experimental antibodies before receiving the infusions, the bNAb combination was ineffective in reducing HIV.
According to the scientists, the prevalence of pre-existing antibody-resistant HIV poses a significant issue in the future. There were no adverse effects in the study, and the infusions were well tolerated.
The authors of the study conclude that, in the absence of ART, combination bNAb therapy can be highly efficient in suppressing HIV for long periods of time, provided that antibody-resistant virus is not present when people start antibody treatment. Larger trials are needed to confirm the findings, but as next-generation bNAbs with higher potency and durability become available, the findings will be more likely to be confirmed.
“there is reason to believe that infrequent administration (i.e., twice a year) of such antibodies, possibly along with a long-acting injectable antiretroviral drug, could lead to ART-free HIV suppression for extended periods (years) in infected individuals,” the authors wrote.