The acute HIV infection: implications for intervention, prevention and development of an effective AIDS vaccine.
ABSTRACT Effective preventive measures against HIV must function near the time of virus transmission to prevent the establishment of a chronic infection. Low-dose SIV/SHIV infections by multiple routes lead to remarkably rapid systemic dissemination of virus and large numbers of infected cells during the initial weeks of the acute infection. Here we describe the narrow time-frame during which potent post-exposure interventions such as anti-retroviral therapy or the administration of high-titered neutralizing antibodies can block the establishment of the in vivo infection. This short window of opportunity is applicable to HIV infections and represents a formidable challenge for developing effective chemoprophylaxis and vaccine approaches.
Article: Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection.[show abstract] [hide abstract]
ABSTRACT: Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.Journal of Virology 11/1997; 71(10):7518-25. · 5.40 Impact Factor