Containment of simian immunodeficiency virus infection: Cellular immune responses and protection from rechallenge following transient postinoculationantiretroviral treatment

To better understand the viral and host factors involved in the establishme nt of persistent productive infection by primate lentiviruses, we varied th e time of initiation and duration of postinoculation antiretroviral treatme nt with tenofovir {9-[2-(R)-(phosphonomethoxy)propyl]adenine} while perform ing intensive virologic and immunologic monitoring in rhesus macaques, inoc ulated intravenously with simian immunodeficiency virus SIVsmE660. Postinoc ulation treatment did not block the initial infection, but we identified tr eatment regimens that prevented the establishment of persistent productive infection, as judged by the absence of measurable plasma viremia following drug discontinuation. While immune responses were heterogeneous, animals in which treatment resulted in prevention of persistent productive infection showed a higher frequency and higher levels of SIV-specific lymphocyte prol iferative responses during the treatment period compared to control animals , despite the absence of either detectable plasma viremia or seroconversion . Animals protected front the initial establishment of persistent productiv e infection were also relatively or completely protected from subsequent ho mologous rechallenge. Even postinoculation treatment regimens that did not prevent establishment of persistent infection resulted in downmodulation of the level of plasma viremia following treatment cessation, compared to the viremia seen in untreated control animals, animals treated with regimens k nown to be ineffective, or the cumulative experience with the natural histo ry of plasma viremia following infection with SIVsmE660. The results sugges t that the host may be able to effectively control SIV infection if the ini tial exposure occurs under favorable conditions of low viral burden and in the absence of ongoing high level cytopathic infection of responding cells. These findings may be particularly important in relation to prospects for control of primate lentiviruses in the settings of both prophylactic and th erapeutic vaccination for prevention of AIDS.