EARLY ESTABLISHMENT OF HIV 1 LATENCY IN RESTING CD4+ T CELLS

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The presence of latently infected, resting CD4+ T cells carrying replication-competent HIV-1 has been demonstrated in chronically infected individuals who are anti-retroviral therapy na?ve as well as in those who are receiving highly active anti-retroviral therapy (HAART). We investigated whether the establishment of a pool of latently infected CD4+ T cells can be blocked by early initiation of HAART following primary infection. Our study demonstrates that despite the successful control of plasma viremia following initiation of HAART in infected individuals as early as 10 days after the onset of symptoms of primary HIV-1 infection, the generation of latently infected, resting CD4+ T cells carrying integrated HIV-1 DNA as well as infectious HIV-1 was not prevented. Furthermore, there was no correlation between either the duration of HAART at the time of study (range: 0.2 to 17 months) or the time of initiation of HAART after the onset of symptoms of primary HIV-1 infection (range: 0.3 to 4 months) and the frequencies of resting CD4+ T cells carrying either integrated HIV-1 DNA or infectious virus. These results underscore the rapidity with which latent reservoirs are established in primary HIV-1 infection and indicate that it is unlikely that early treatment during primary infection can prevent establishment of a pool of latently infected, resting CD4+ T cells as long as treatment is initiated after plasma viremia becomes evident.