HIV replication persists in patients receiving HAART despite undetectable plasma virus

OBJECTIVE: To determine if there is ongoing HIV replication in patients receiving highly active antiretroviral therapy (HAART) who have less than 50 HIV RNA copies/ml in plasma. METHODS: Cells from eleven patients receiving HAART for a year or longer, nine of whom had also received intermittent interleukin-2 therapy, who had less than 50 copies of viral RNA in plasma, as determined by RT-PCR, were examined for the presence of HIV RNA using a nested RT-PCR assay (sensitivity, 20 copies/10(6) cells). Proviral DNA was determined using a semi-quantitative PCR technique. A micro culture assay was used to culture HIV from resting CD4+ T cells. RESULTS: By nested RT-PCR, HIV RNA was detected in the peripheral blood mononuclear cells of 8/11 patients, despite > 1 year of HAART and undetectable plasma HIV RNA (< 50 copies/ml). Proviral DNA was detectable in the cells of all patients, although a nested assay (sensitivity ≊ 1 copy/10(6) cells) was required to detect DNA in two patients with undetectable cellular HIV RNA. HIV could not be cultured from either of these patients using 2-5 million resting CD4+ T cells. However, both of these patients had detectable HIV RNA in their lymphoid tissue (lymph node/gut associated lymphoid tissue). Of note, it has been previously shown that resting CD4+ T cells consistently harbor latent replication-compentent HIV in patients receiving HAART. CONCLUSIONS: HIV RNA can be detected in cells by RT-PCR indicating an ongoing viral replication in these cells. Persistent HIV-1 replication can be found in peripheral blood cells or lymphoid tissue of patients receiving HAART for greater than 1 year, despite absence of detectable plasma virus. Nested RT-PCR appears to be a highly sensitive method for detecting ongoing viral replication in such patients.

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