This small study had 2 phases, but patients saw HIV viral suppression for about 40 weeks after receiving the combination therapy infusions.
Combination therapy with 2 HIV-specific broadly neutralizing anti-HIV antibodies (bNAbs) may be a future alternative for those with HIV instead of daily antiretroviral therapy (ART), according to a paper published in Nature.
Investigators from National Institute of Allergy and Infectious Diseases (NIAID) conducted a 2-comopnent clinical trial in order to determine the ability of 2 HIV-specific bNAbs (3BNC117 and 10-1074) to act as long-acting antiviral agents that inhibit viral replication in HIV patients.
The first part of the study involved a randomized, double-blind, placebo-controlled trial for 14 patients in the acute and early phases of HIV infection who were enrolled in ART. Between September 2018 and January 2021, the patients were taken off ART before their first infusion of bNAbs or placebo. They were given 2 infusions in the first month and once per month thereafter for a total of 8 infusions over 24 weeks. The investigators measured the patients’ CD4 T-cell counts and HIV levels every 2 weeks, they noted.
The study authors found that none of the 7 total patients who received combination therapy had to restart ART before 28 weeks post-infusion compared to 6 of the 7 patients who received placebo. Median time off ART was 39 weeks for the bNAbs group and 9 weeks for the placebo group, the study authors noted in a press release.
In the second part of the study, 5 ART-naïve HIV patients were enrolled in an open-label, single-arm trial. At the end of the study period, 2 of the 5 patients maintained complete suppression of the virus for an average of 41 weeks, the study authors reported.
If the participants had a resistant HIV strain, the study authors found the bNAbs combination therapy to be ineffective. They warned that antibody-resistant HIV is a threat to effective therapies going forward.
“Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives,” the study authors wrote.
The study authors wrote that infusions of 3BNC117 and 10-1074 were well-tolerated without any serious adverse events related to the infusions. The investigators noted that is essential for larger studies to confirm their findings, as their studies were conducted with admittedly small sample sizes. Their total number of infusions was also limited to 8, which could be further investigated in larger trials, too.
“As the next generation of bNAbs with increased breadth and prolonged half-lives (>60 days) become available, there is a reason to believe that the infrequent administration (that is, 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 individuals with infection,” the study authors concluded.