Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy

Context Despite suppressive treatment with highly active antiretroviral the rapy (HAART), replication-competent virus can still be isolated from periph eral blood mononuclear cells and genital cells of many individuals receivin g 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 HAA RT. 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 R NA 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 p olymerase chain reaction able to quantify cell-free virion RNA to a lower l imit 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 per ipheral 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' g enital fluids compared with blood plasma and in 12 patients were undetectab le. Conclusions These data suggest that low-level replication of HIV-1 in patie nts taking suppressive HAART may be demonstrated not only in peripheral blo od mononuclear cells but also in peripheral plasma as cell-free virion RNA. Complete ablation of viral replication may require intensification of anti retroviral therapies beyond standard suppressive HAART.