Short-course raltegravir intensification does not increase 2 long terminal repeat episomal HIV-1 DNA in patients on effective antiretroviral therapy.

To the Editor—Controversy exists about whether human immunodeficiency virus type 1 (HIV-1) replication persists in patients receiving effective antiretroviral therapy. Residual viremia can often be detected in such patients by sensitive quantitative polymerase chain reaction assays, but the source of this viremia is unknown [1]. Possibilities include ongoing cycles of HIV-1 replication, long-lived HIV-1–infected cells that continuously or intermittently produce virus, or both. If residual plasma viremia is derived from ongoing HIV-1 replication, intensification of an effective regimen with another potent antiretroviral drug should lower viremia. Such treatment intensification studies have been conducted with different classes of antiretroviral agents (nucleoside reverse-transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, protease inhibitors, and the integrase inhibitor raltegravir), and none has shown reduction in residual viremia [2–6]. However, Buzon et al [7] showed transient increases in episomal (2-Long Terminal Repeat [2-LTR] circle) HIV-1 DNA levels in 13 of 45 patients after raltegravir intensification, suggesting raltegravir blocked ongoing HIV-1 replication without affecting plasma viremia. Moreover, Yukl et al [5] showed reductions in unspliced HIV-1 RNA levels in