The effect of raltegravir intensification on low-level residual viremia in
HIV-infected patients on antiretroviral therapy: a randomized controlled trial.
Author(s): 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 JW, Eron JJ; AIDS Clinical Trials Group A5244 team.
Collaborators: Leavitt R, Philpotts B, Donoval BA, Levaro R, Martinez A, Demeter
LM, D'Aquila R, Pettinelli C, Janik J, Springer H, Jennings A.
Affiliation(s): Massachusetts General Hospital and Ragon Institute, Boston, Massachusetts, United
States of America. rgandhi@partners.org
Publication date & source: 2010, PLoS Med. , 7(8). pii: e1000321
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/mm(3), 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.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00515827
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