Residual viral replication persists in a significant proportion of human immunodeficiency virus (HIV)-infected patients receiving potent antiretroviral therapy. To determine the source of this virus, levels of HIV RNA and DNA from lymphoid tissues and levels of viral RNA in serum, cerebrospinal fluid (CSF), and genital secretions in 28 patients treated for ≤2.5 years with indinavir, zidovudine, and lamivudine were examined. Both HIV RNA and DNA remained detectable in all lymph nodes. In contrast, HIV RNA was not detected in 20 of 23 genital secretions or in any of 13 CSF samples after 2 years of treatment. HIV envelope sequence data from plasma and lymph nodes from 4 patients demonstrated sequence divergence, which suggests varying degrees of residual viral replication in 3 and absence in 1 patient. In patients receiving potent antiretroviral therapy, the greatest virus burden may continue to be in lymphoid tissues rather than in central nervous system or genitourinary compartments.
Bibliographical noteFunding Information:
Financial support: National lnstitutes of Health (grants AI-43752 to J.K.W.; AI-27670, AI-38858, AI-29164, and AI-36214 to D.D.R.; HD-37260; and RR-00046); Swiss National Science Foundation (grant 84AD-046176 to H.F.G.); Medical Research Council Research fellowship (G81/ 298 to S.D.W.F.); Fogarty Foundation (to A.J.L.B.); Merck Research Laboratories (unrestricted educational grant); Research Center for AIDS and HIV Infection of the San Diego Veterans Affairs Healthcare System; VA Career Development Award (to J.K.W.).