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Raltegravir (RAL) intensification does not reduce low-level residual viremia in HIV-1-infected patients on antiretroviral therapy (ART): results from ACTG A5244
Presented by Rajesh Gandhi (United States).
R. Gandhi1, S. Zheng2, R. Bosch2, E. Chan2, D. Margolis3, S. Read4, B. Kallungal5, H. Sprenger6, J. Janik6, J. Jacobson7, A. Wiegand8, M. Kearney8, S. Palmer9, J. Coffin10, J. Mellors11, J. Eron3, AIDS Clinical Trials Group A5244 Team
1Massachusetts General Hospital / Harvard Medical School, Boston, United States, 2Harvard School of Public Health, Boston, United States, 3University of North Carolina, Chapel Hill, United States, 4National Instititues of Health, Bethesda, United States, 5Social & Scientific Systems, Inc., Silver Spring, United States, 6Frontier Science Technology and Research Foundation, Amherst, United States, 7Drexel University College of Medicine, Philadelphia, United States, 8National Cancer Institute-Frederick, Frederick, United States, 9Karolinska Institute, Stockholm, Sweden, 10Tufts University, Boston, United States, 11University of Pittsburgh Medical Center, Pittsburgh, United States
Background: Most HIV-1-infected patients on long-term successful ART (plasma viral load (VL) < 50 copies(c)/mL) have residual viremia detectable with more sensitive assays. We assessed whether adding raltegravir lowered residual viremia in such patients.
Methods: The study population was HIV-1-infected patients on ART for ≥12 months, VL below limits of detection for ≥6 months using commercial assays and detectable viremia (plasma VL>0.2 c/mL) by single copy assay (SCA). Subjects were randomized to add either RAL or placebo to their ART regimen for 12 weeks; subjects then crossed-over to the alternative agent for an additional 12 weeks while continuing pre-study ART. The primary endpoint was plasma VL by SCA averaged between weeks 10 and 12.
Results: 53 subjects were enrolled. Median age was 49 years; 91% were men. Median CD4 cell count was 589/mm3 and median screening VL was 1.7 c/mL. The median VL at week 10/12 did not differ between the RAL-intensified (n=25) and placebo-intensified (n=24) groups (1.1 vs. 1.7 c/mL, p=0.80, Wilcoxon test), nor did the median change in VL from baseline to week 10/12 (-0.3 and -0.1 c/mL, p=0.52). There was also no significant change in VL from weeks 10/12 to weeks 22/24 after subjects crossed-over from RAL to placebo or from placebo to RAL. There was a trend towards greater CD4 cell count increase from baseline to week 12 in the RAL-intensified compared with the placebo group (+42 vs. -44 cells/mm3, p=0.08), which reversed after the cross-over.
Conclusion: In this large, randomized, double-blind cross-over study, 12 weeks of RAL intensification did not reduce low-level plasma viremia in patients on currently-recommended ART. This finding argues strongly against the hypothesis that ongoing, complete cycles of viral replication and integration are the main source of residual viremia. New therapeutic strategies to eliminate reservoirs that produce residual viremia will be required to eradicate HIV-1 infection.
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