Research ArticleHIV

The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation

See allHide authors and affiliations

Science Translational Medicine  09 Oct 2019:
Vol. 11, Issue 513, eaaw5589
DOI: 10.1126/scitranslmed.aaw5589

Au revoir HIV reservoir?

Curing HIV requires eliminating the latent viral reservoir. To better understand how this reservoir is formed, Abrahams et al. examined longitudinal samples from nine South African women with HIV. HIV was grown from resting CD4+ T cells isolated after several years of antiretroviral therapy (ART) and compared to viral sequences from longitudinal samples collected before ART. They found that in most subjects, reservoir viral sequences were related to viruses present at the time of ART initiation. These results suggest that the majority of the latent reservoir is seeded in response to therapy and likely is not continually formed prior to ART. HIV treatment and cure efforts could potentially exploit this information to limit the size of the reservoir when treatment is initiated.


Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. This reservoir forms even when ART is initiated early after infection, but the dynamics of its formation are largely unknown. The viral reservoirs of individuals who initiate ART during chronic infection are generally larger and genetically more diverse than those of individuals who initiate therapy during acute infection, consistent with the hypothesis that the reservoir is formed continuously throughout untreated infection. To determine when viruses enter the latent reservoir, we compared sequences of replication-competent viruses from resting peripheral CD4+ T cells from nine HIV-positive women on therapy to viral sequences circulating in blood collected longitudinally before therapy. We found that, on average, 71% of the unique viruses induced from the post-therapy latent reservoir were most genetically similar to viruses replicating just before ART initiation. This proportion is far greater than would be expected if the reservoir formed continuously and was always long lived. We conclude that ART alters the host environment in a way that allows the formation or stabilization of most of the long-lived latent HIV-1 reservoir, which points to new strategies targeted at limiting the formation of the reservoir around the time of therapy initiation.

View Full Text

Stay Connected to Science Translational Medicine