Residual HIV-1 RNA in Blood Plasma of Patients Taking Suppressive Highly Active Antiretroviral Therapy

Abstract

CONTEXT: Despite suppressive treatment with highly active antiretroviral therapy (HAART), replication-competent virus can still be isolated from peripheral blood mononuclear cells and genital cells of many individuals receiving suppressive HAART. OBJECTIVE: To determine whether free virion RNA can be detected in the blood plasma and/or genital tract fluids from patients receiving suppressive HAART. DESIGN: Prospective cohort study conducted from November 1998 to May 1999. SETTING: Academic medical center. PATIENTS: Human immunodeficiency virus 1-infected individuals (20 men and 2 women) shown in our laboratories to have fewer than 50 copies/mL of HIV-1 RNA in peripheral blood plasma while taking suppressive HAART. MAIN OUTCOME MEASURES: Free virion RNA levels in peripheral blood plasma and genital fluids, quantified using an ultrasensitive reverse transcriptase polymerase chain reaction able to quantify cell-free virion RNA to a lower limit of 5 copies/mL and qualitatively detect viral RNA below this level. RESULTS: In all 22 patients, residual viral RNA could be detected in the peripheral blood plasma (mean level, 17 copies/mL). The presence of viral RNA suggests that ongoing viral replication is occurring, albeit at low levels, in each patient evaluated. Viral RNA levels were lower in most patients' genital fluids compared with blood plasma and in 12 patients were undetectable. CONCLUSIONS: These data suggest that low-level replication of HIV-1 in patients taking suppressive HAART may be demonstrated not only in peripheral blood mononuclear cells but also in peripheral plasma as cell-free virion RNA. Complete ablation of viral replication may require intensification of antiretroviral therapies beyond standard suppressive HAART.