Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.

TitleChanges in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.
Publication TypeJournal Article
Year of Publication2015
AuthorsKelesidis T, Tran TTien T, Stein JH, Brown TT, Moser C, Ribaudo HJ, Dubé MP, Murphy R, Yang OO, Currier JS, McComsey GA
JournalClin Infect Dis
Volume61
Issue4
Pagination651-60
Date Published2015 Aug 15
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Atazanavir Sulfate, Biomarkers, Darunavir, Female, HIV Infections, Humans, Inflammation, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Raltegravir Potassium, Treatment Outcome
Abstract

BACKGROUND: It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs).

METHODS: In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control.

RESULTS: Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups.

CONCLUSIONS: Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens.

CLINICAL TRIALS REGISTRATION: NCT00811954 and NCT00851799.

DOI10.1093/cid/civ327
Alternate JournalClin. Infect. Dis.
PubMed ID25904376
PubMed Central IDPMC4542595
Grant ListAI 068636 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI56933 / AI / NIAID NIH HHS / United States
AI69471 / AI / NIAID NIH HHS / United States
HL095126 / HL / NHLBI NIH HHS / United States
HL095132 / HL / NHLBI NIH HHS / United States
K24 AI120834 / AI / NIAID NIH HHS / United States
U01 AI025915 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States