Residual human immunodeficiency virus type 1 infection in lymphoid tissue during highly active antiretroviral therapy: Quantitation and virus characterization

HIV-1 can persist in infected patients despite undetectable plasma viremia, To characterize the residual viral load, repetitive blood and tonsillar sa mples were collected from 11 HIV-1-positive individuals before and during 9 6 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 limi ting dilution assay. Genotypic resistance analyses and biological character ization were performed on plasma virus, blood, and tonsillar isolates. Tons illar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log(10), respectively, but 10(3)-10(4) cells, less than 0.5% of the total body CD4() T cell population carrying infectious HIV-1 provirus, remained involved i n active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of less than or equal to 10(6) latently infected CD4(+) cells. Plasma HIV-1 RNA decline of >1.5 log(10) 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 r eplicating HIV-1 continuously declines during prolonged antiretroviral ther apy. Thus, although viral eradication seems unlikely, antiretroviral therap y may induce an extended period of virologic latency in HIV-1-positive indi viduals.