Preexposure prophylaxis (PrEP) with antiretroviral drugs constitutes a promising strategy for HIV prevention. Potent PrEP regimens with
reverse transcriptase inhibitors can prevent detectable SHIV
infection in a repeated low-dose macaque model that resembles human transmission, supporting plans to quickly move this approach into human trials. However, the possibility remains that extremely low levels of virus replication could nonetheless occur during PrEP and seed viral reservoirs in tissues. Therefore, seemingly protected macaques may harbor occult virus that may be initially contained by cytotoxic T cells, but could emerge later. To explore this possibility, we studied whether CD8(+) cells suppress
viremia in four rhesus macaques apparently protected by daily or intermittent
Truvada (
FTC and
tenofovir) during 14 low-dose, rectal SHIV(SF162P3) challenges and during a subsequent
drug washout period. CD8(+) cells were efficiently ablated with
antibodies in these and two additional control macaques that were previously infected but had reached undetectable virus set points. During 4 weeks of follow-up, all four macaques remained free of plasma
viremia and provirus in blood lymphocytes. In contrast, plasma
viremia resurged to 10(6) to 10(7) copies per milliliter within 2 weeks in both control macaques. Thus, these results indicate that the undetectable
viremia in the PrEP-protected macaques was not due to CD8(+) cells that were containing a low-level
infection. Rather, the PrEP treatment created conditions in which
infection was prevented, eliminated, or controlled by unknown mechanisms. These data provide important information for PrEP usage to prevent HIV transmission, and fully support the continued pursuit of PrEP prevention measures in humans.