Residual Human Immunodeficiency Virus Type 1 Infection in Lymphoid Tissue during Highly Active Antiretroviral Therapy: Quantitation and Virus Characterization

Abstract

HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the residual viral load, repetitive blood and tonsillar samples were collected from 11 HIV-1-positive individuals before and during 96 weeks of therapy with zidovudine, lamivudine, and indinavir. HIV-1 RNA in tonsils was quantified by RT-PCR and infectious HIV-1 provirus by the limiting dilution assay. Genotypic resistance analyses and biological characterization were performed on plasma virus, blood, and tonsillar isolates. Tonsillar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log₁₀, respectively, but 10³-10⁴ cells, less than 0.5% of the total body CD4⁺ T cell population carrying infectious HIV-1 provirus, remained involved in active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of ≤10⁶ latently infected CD4⁺ cells. Plasma HIV-1 RNA decline of >1.5 log₁₀ during the first 2 weeks of therapy may indicate low levels of this latent reservoir. Whereas the reservoir of latently infected cells remains stable, actively replicating HIV-1 continuously declines during prolonged antiretroviral therapy. Thus, although viral eradication seems unlikely, antiretroviral therapy may induce an extended period of virologic latency in HIV-1-positive individuals.