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

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 vire...

Full description

Saved in:

Bibliographic Details
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
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Author contributions: J.M.C., J.W.M., R.F.S., and F.M. designed research; J.B.D., S.Y.K., A.M.W., S.E.P., L.C., A.O., M.C., A.S., T.B., M.F.K., J.M.M., C.A.R., and F.M. performed research; J.B.D., S.Y.K., S.J.G., M.A.P., J.M.C., R.F.S., and F.M. analyzed data; and J.B.D., S.Y.K., J.M.C., J.W.M., R.F.S., and F.M. wrote the paper. 2Present address: Department of Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, SE-171 82 Solna, Sweden. Contributed by J. M. Coffin, March 23, 2009 1J.B.D. and S.Y.K. contributed equally to this work.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0903107106