Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat
Cynthia L. Gay, Katherine S. James, Marina Tuyishime, Shane D. Falcinelli, Sarah Joseph, Matthew Moeser, Brigitte Allard, Jennifer Kirchherr, Matthew L. Clohosey, Samuel L M Raines, David C. Montefiori, Xiaoying Shen, Robert J. Gorelick, Lúcio Gama, Adrian B. McDermott, Richard A. Koup, John R. Mascola, Michelle Floris-Moore, JoAnn Kuruc, Guido Ferrari, Joseph J. Eron, Nancie M. Archin, David M. Margolis
Abstract
We tested the combination of a broadly neutralizing HIV antibody with the latency reversal agent vorinostat (VOR). Eight participants received 2 month-long cycles of VRC07-523LS with VOR. Low-level viremia, resting CD4+ T-cell-associated HIV RNA (rca-RNA) was measured, and intact proviral DNA assay (IPDA) and quantitative viral outgrowth assay (QVOA) were performed at baseline and posttreatment. In 3 participants, IPDA and QVOA declines were accompanied by significant declines of rca-RNA. However, no IPDA or QVOA declines clearly exceeded assay variance or natural decay. Increased resistance to VRC07-523LS was not observed. This combination therapy did not reduce viremia or the HIV reservoir. Clinical Trials Registration. NCT03803605.