13th International HIV Drug Resistance Workshop


8–12 June 2004, Tenerife Sur-Costa Adeje, Canary Islands, Spain


MONKEY BUSINESS: INSIGHTS INTO AIDS VIRUS PATHOGENESIS FROM STUDIES IN NON-HUMAN PRIMATES

Antiviral Therapy 2004; 9:S2 (abstract P2)

JD Lifson
AIDS Vaccine Program, SAIC Frederick, Inc., National Cancer Institute, Frederick, Md., USA

The error-prone replication mechanism employed by the primate lentiviruses is capable of generating extensive diversity in a virus population. In the face of environmental selection pressures, this process can produce viruses that are adapted, with varying degrees of fitness, to a wide variety of immunological and pharmacological environments. Drug-resistant mutant viruses and immune escape mutant viruses selected by both humoral and cellular arms of the immune system are well documented examples of this process. Nonhuman primate models offer multiple advantages in efforts to understand the processes that drive and control such selection in vivo. These include the ability to inoculate animals at defined times, via defined routes, with defined doses of defined viruses of known sequence and pathogenicity. Compared to studies of HIV-infected patients, non-human primate models may also provide opportunities for more extensive sampling of blood or tissues, especially at defined early time points relative to inoculation, as well as greater flexibility for more intensive experimental interventions such as initiation, modification or cessation of antiretroviral therapy (ART), or immunological perturbation (as in depletion of CD8+ lymphocytes through administration of mAbs). The presentation will review illustrative examples of selection processes in vivo in SIV infected macaques, including selection of mutants following transmission of wild-type viruses and development of reversions or compensatory mutations in macaques inoculated with mutant viruses. Model systems presented will include observational natural history studies, as well as interventional studies, such as a model of transient ART during primary infection and therapeutic vaccination regimens in chronically infected macaques. Additional systems showing promise for the study of resistance to antiretroviral drugs in vivo in non-human primates may also be presented.

Presenting author: JD Lifson

2004-06-08
P2

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