Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 23; pp. 9403 - 9408
• Main Authors: Dinoso, J.B, Kim, S.Y, Wiegand, A.M, Palmer, S.E, Gange, S.J, Cranmer, L, O'Shea, A, Callender, M, Spivak, A, Brennan, T, Kearney, M.F, Proschan, M.A, Mican, J.M, Rehm, C.A, Coffin, J.M, Mellors, J.W, Siliciano, R.F, Maldarelli, F
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09-06-2009; National Acad Sciences
• Subjects: Adult; Anti-HIV Agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; Antiretrovirals; Antiviral agents; Antivirals; Arts; Biological Sciences; Drug resistance; Drug therapy; Drugs; Efavirenz; highly active antiretroviral therapy; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Infection; Infections; Lopinavir; Pharmacology; Prospective Studies; Replication; Ribonucleic acid; Ritonavir; RNA; T lymphocytes; Viremia; Viremia - drug therapy; Virus Replication; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0903107106

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.