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The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: A randomized controlled trial

Gandhi, RT and Zheng, L and Bosch, RJ and Chan, ES and Margolis, DM and Read, S and Kallungal, B and Palmer, S and Medvik, K and Lederman, MM and Alatrakchi, N and Jacobson, JM and Wiegand, A and Kearney, M and Coffin, JM and Mellors, JW and Eron, JJ (2010) The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: A randomized controlled trial. PLoS Medicine, 7 (8). ISSN 1549-1277

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Abstract

Background:Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods. We assessed whether adding raltegravir lowered the level of residual viremia in such patients. Methods and Findings:Patients receiving ART who had plasma HIV-1 RNA levels below 50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to add either raltegravir or placebo to their ART regimen for 12 weeks; patients then crossed-over to the other therapy for an additional 12 weeks while continuing pre-study ART. The primary endpoint was the plasma HIV-1 RNA by SCA averaged between weeks 10 and 12 (10/12) compared between treatment groups. Fifty-three patients were enrolled. The median screening HIV-1 RNA was 1.7 copies/mL. The HIV-1 RNA level at weeks 10/12 did not differ significantly between the raltegravir-intensified (n = 25) and the placebo (n = 24) groups (median 1.2 versus 1.7 copies/mL, p= 0.55, Wilcoxon rank sum test), nor did the change in HIV-1 RNA level from baseline to week 10/12 (median -0.2 and -0.1 copies/mL, p = 0.71, Wilcoxon rank sum test). There was also no significant change in HIV-1 RNA level from weeks 10/12 to weeks 22/24 after patients crossed-over. There was a greater CD4 cell count increase from baseline to week 12 in the raltegravir-intensified group compared with the placebo group (+42 versus -44 cells/mm3, p= 0.082, Wilcoxon rank sum test), which reversed after the cross-over. This CD4 cell count change was not associated with an effect of raltegravir intensification on markers of CD4 or CD8 cell activation in blood. Conclusion:In this randomized, double-blind cross-over study, 12 weeks of raltegravir intensification did not demonstrably reduce low-level plasma viremia in patients on currently recommended ART. This finding suggests that residual viremia does not arise from ongoing cycles of HIV-1 replication and infection of new cells. New therapeutic strategies to eliminate reservoirs that produce residual viremia will be required to eradicate HIV-1 infection.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gandhi, RT
Zheng, L
Bosch, RJ
Chan, ES
Margolis, DM
Read, S
Kallungal, B
Palmer, S
Medvik, K
Lederman, MM
Alatrakchi, N
Jacobson, JM
Wiegand, A
Kearney, M
Coffin, JM
Mellors, JWjwm1@pitt.eduJWM1
Eron, JJ
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
UNSPECIFIEDLeavitt, RandiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDPhilpotts, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDDonoval, Betty AUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDLevaro, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDMartinez, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDDemeter, Lisa MUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDD'Aquila, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDPettinelli, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDJanik, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDSpringer, HeatherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
UNSPECIFIEDJennings, AmyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 August 2010
Date Type: Publication
Journal or Publication Title: PLoS Medicine
Volume: 7
Number: 8
DOI or Unique Handle: 10.1371/journal.pmed.1000321
Refereed: Yes
ISSN: 1549-1277
MeSH Headings: Anti-HIV Agents--pharmacology; Anti-HIV Agents--therapeutic use; Antiretroviral Therapy, Highly Active--methods; Cross-Over Studies; Double-Blind Method; Female; HIV Infections--blood; HIV Infections--drug therapy; HIV-1--drug effects; HIV-1--metabolism; Humans; Male; Middle Aged; Pyrrolidinones--pharmacology; Pyrrolidinones--therapeutic use; Viral Load--methods; Viremia--blood; Viremia--drug therapy
Other ID: NLM PMC2919424
PubMed Central ID: PMC2919424
PubMed ID: 20711481
Date Deposited: 21 Aug 2012 14:18
Last Modified: 22 Jun 2021 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/13395

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