Rajesh T. Gandhi, MD reviewing Bar KJ et al. N Engl J Med 2016 Nov 9.

A broadly neutralizing antibody, VRC01, delayed HIV rebound when antiretroviral therapy was stopped, but selection of resistance to the antibody was common.

Broadly neutralizing antibodies (bNAbs) against HIV are being evaluated for prevention and treatment of infection. A bNAb called VRC01 was previously shown to decrease HIV RNA levels in viremic patients (Sci Transl Med 2015; 7:319ra206). To evaluate whether VRC01 can delay HIV rebound when antiretroviral therapy (ART) is withdrawn, two single-arm trials were conducted, one by the AIDS Clinical Trials Group (ACTG) and the other at the National Institutes of Health (NIH).

Both trials enrolled HIV-infected participants who were virologically suppressed on ART. In the ACTG study, 14 participants had up to three infusions of VRC01 every 3 weeks; ART was stopped 1 week after the first infusion. In the NIH trial, 10 participants received VRC01 infusions 3 days before and 2 and 4 weeks after ART was withdrawn and then monthly thereafter. Comparisons were made to historical controls that underwent ART interruption without receiving an immunotherapeutic intervention.

Following ART discontinuation, all participants had viral rebound. The median time to HIV rebound was 4.0 weeks in the ACTG trial and 5.6 weeks in the NIH trial. At week 4 after ART interruption, a significantly higher proportion of VRC01-treated participants were still virally suppressed: 38% in the ACTG trial, 80% in the NIH trial, and only 13% of historical controls. However, by 8 weeks after ART interruption, viral suppression did not differ between the groups. Selection of virus that was VRC01-resistant was frequent during the treatment interruption.

CITATION(S):

Bar KJ et al. Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N Engl J Med 2016 Nov 9; [e-pub].

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