No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy.

TitleNo effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2012
AuthorsGandhi RT, Coombs RW, Chan ES, Bosch RJ, Zheng L, Margolis DM, Read S, Kallungal B, Chang M, Goecker EA, Wiegand A, Kearney M, Jacobson JM, D'Aquila R, Lederman MM, Mellors JW, Eron JJ
Corporate AuthorsAIDS Clinical Trials Group(ACTG) A5244 Team
JournalJ Acquir Immune Defic Syndr
Volume59
Issue3
Pagination229-35
Date Published2012 Mar 1
ISSN1944-7884
KeywordsAnti-HIV Agents, CD4 Lymphocyte Count, DNA, Viral, HIV Infections, HIV Long Terminal Repeat, HIV-1, Humans, Lymphocyte Activation, Polymerase Chain Reaction, Pyrrolidinones, Raltegravir Potassium, RNA, Viral, T-Lymphocytes, Viremia, Virus Replication
Abstract

BACKGROUND: Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.

METHODS: We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.

RESULTS: Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.

CONCLUSIONS: In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.

DOI10.1097/QAI.0b013e31823fd1f2
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID22083073
PubMed Central IDPMC3423091
Grant List1U01AI068636 / AI / NIAID NIH HHS / United States
2P30 AI060354-06 / AI / NIAID NIH HHS / United States
AI 068634 / AI / NIAID NIH HHS / United States
AI-38858 / AI / NIAID NIH HHS / United States
AI-68636 / AI / NIAID NIH HHS / United States
G08 LM008830 / LM / NLM NIH HHS / United States
G08 LM008830-03 / LM / NLM NIH HHS / United States
G08LM008830-01 / LM / NLM NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI060354-06 / AI / NIAID NIH HHS / United States
P30-AI-27757 / AI / NIAID NIH HHS / United States
R01 AI066992 / AI / NIAID NIH HHS / United States
R01 AI066992-04A1 / AI / NIAID NIH HHS / United States
R01 AI066992-05 / AI / NIAID NIH HHS / United States
U01 AI 694722 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636-05 / AI / NIAID NIH HHS / United States
U01 AI069423 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States