Initiation of Antiretroviral Therapy 48 Hours after Infection with Simian Immunodeficiency Virus Potently Suppresses Acute-Phase Viremia and Blocks the Massive Loss of Memory CD4+ T Cells but Fails To Prevent Disease

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 2089-0460, USA.
Journal of Virology (Impact Factor: 4.44). 06/2009; 83(14):7099-108. DOI: 10.1128/JVI.02522-08
Source: PubMed


We investigated whether a 28-day course of potent antiretroviral therapy, initiated at a time point (48 h postinoculation)
following simian immunodeficiency virus (SIV) inoculation when the acquisition of a viral infection was virtually assured,
would sufficiently sensitize the immune system and result in controlled virus replication when treatment was stopped. The
administration of tenofovir 48 h after SIV inoculation to six Mamu-A*01-negative rhesus macaques did, in fact, potently suppress virus replication in all of the treated rhesus macaques, but plasma
viral RNA rapidly became detectable in all six animals following its cessation. Unexpectedly, the viral set points in the
treated monkeys became established at two distinct levels. Three controller macaques had chronic phase virus loads in the
range of 1 × 103 RNA copies/ml, whereas three noncontroller animals had set points of 2 × 105 to 8 × 105 RNA copies/ml. All of the noncontroller monkeys died with symptoms of immunodeficiency by week 60 postinfection, whereas
two of the three controller animals were alive at week 80. Interestingly, the three controller macaques each carried major
histocompatibility complex class I alleles that previously were reported to confer protection against SIV, and two of these
animals generated cytotoxic T-lymphocyte escape viral variants during the course of their infections.

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