Beyond antiretroviral therapy: early interventions to control HIV-1 infection.

The HIV-1 reservoir is established very early after transmission when proviruses become integrated in the genome of long-lived immune cells. Three to 6 days after infection, intracellular HIV-1 DNA in CD4þ T cells and virions attached to antigen-presenting cells can be detected in regional draining lymph nodes [1]. The rapid dissemination of HIV-1 in humans corresponds to observations in nonhuman primates (NHPs) in which simian immunodeficiency virus (SIV) DNA is detectable in lymph nodes and gastrointestinal mucosa on day 3 following infection, even in the absence of detectable plasma viremia [2]. Significantly, antiretroviral therapy (ART) initiated day 3 postinfection in NHPs delayed but did not prevent viral rebound following treatment interruption after 24 weeks of ART [2]. Thus, although ARTeffectively suppresses SIV/HIV-1 replication, it has no effect on already integrated proviruses and cannot prevent the establishment of a latent viral reservoir.