Broad and potent monoclonal anti-HIV-1 antibodies (bNabs) comprise a promising class of immunotherapeutics that have the potential to suppress HIV-1 infection, increase the rate of infected cell clearance and enhance anti-HIV immunity. However, bNabs have only been tested in short term studies and their effects on the intact latent reservoir have not been interrogated in depth. Here we report on a clinical study in which people living with HIV who started ART during chronic infection received 7 doses of a combination of two bNabs over a period of 20 weeks in the presence or absence of antiretroviral therapy (ART).
We conducted a phase 1b, open label, randomized clinical trial of the combination of two bNabs, 3BNC117 and 10-1074, in the presence or absence of ART, including two study groups of people living with HIV-1 on suppressive ART for at least 12 months prior to entry (NCT03526848). Participants in Group 1 discontinued ART 2 days after the first 3BNC117 and 10-1074 infusions, while participants in Group 2 remained on ART during the period of antibody infusions through week 26 (Fig. 1a). ART was resumed according to pre-specified criteria. Participants in both groups received up to seven infusions of 30 mg/kg of each antibody over the course of 20 weeks, and were followed for a total of 48 weeks from enrollment.
Of the 26 (23 male, 3 female) enrolled participants, 18 and 8 were randomized to Group 1 or 2, respectively. Repeated antibody infusions over the course of 20 weeks were generally safe and well-tolerated. Without pre-screening for antibody sensitivity Group 1 participants maintained viral suppression for a median of 28.5 weeks in the absence of ART which was significantly longer than after 3 infusions over 6 weeks and historical controls from non-interventional ATI studies (Fig.1b, Log-rank Mantel-Cox P = 0.0224 and P < 0.0001, respectively). Rebound viremia generally occurred after one of the two antibodies reached a concentration below 10 micrograms per milliliter and 2 of 17 participants in Group 1 that underwent ATI maintained viral suppression for at least 48 weeks (Fig. 1b).
We conclude that combination anti-HIV-1 antibody therapy can maintain viral suppression for as long as bNAb levels remain therapeutic. Furthermore, post-treatment control for 48 weeks and longer was observed in 12% of the study cohort. We are evaluating the immunomodulatory effects on the size and composition of the latent reservoir.