PT  - JOURNAL ARTICLE
AU  - Yehuda Z. Cohen
AU  - Julio C. C. Lorenzi
AU  - Lisa Krassnig
AU  - John P. Barton
AU  - Leah Burke
AU  - Joy Pai
AU  - Ching-Lan Lu
AU  - Pilar Mendoza
AU  - Thiago Y. Oliveira
AU  - Christopher Sleckman
AU  - Katrina Millard
AU  - Allison L. Butler
AU  - Juan P. Dizon
AU  - Shiraz A. Belblidia
AU  - Maggi Witmer-Pack
AU  - Irina Shimeliovich
AU  - Roy M. Gulick
AU  - Michael S. Seaman
AU  - Mila Jankovic
AU  - Marina Caskey
AU  - Michel C. Nussenzweig
TI  - Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117
AID  - 10.1101/324509
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 324509
4099  - http://biorxiv.org/content/early/2018/05/25/324509.short
4100  - http://biorxiv.org/content/early/2018/05/25/324509.full
AB  - A clinical trial was performed to evaluate 3BNC117, a potent anti_HIV_1 antibody, in infected individuals during suppressive antiretroviral therapy (ART) and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative outgrowth assay (Q2VOA) at entry and after 6 months, prior to ATI. Although there were no significant quantitative changes in the size of the reservoir, the composition of circulating reservoir clones varied over the 6_month period before treatment interruption in a manner that did not correlate with antibody sensitivity. The neutralization profile obtained from the reservoir by Q2VOA was predictive of time to rebound after ATI, and thus of antibody efficacy. Although 3BNC117 binding site amino acid variants found in rebound viruses pre_existed in the latent reservoir, only 3 of 217 rebound viruses were identical to 868 latent viruses. Instead many of the rebound viruses appeared to be recombinants, even in individuals with resistant reservoir viruses. By incorporating the possibility of recombination, 63% of the rebound viruses could have derived from the observed latent reservoir. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating reservoir, but instead appear to represent recombinants.Summary In the setting of a clinical trial evaluating the anti_HIV_1 antibody 3BNC117, Cohen et al. demonstrate that rebound viruses that emerge following interruption of antiretroviral therapy are distinct from circulating latent viruses. However, rebound viruses often appear to be recombinants between isolated latent viruses.