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Sex-related differences in inflammatory and immune activation markers before and after combined antiretroviral therapy initiation

  • Author(s): Mathad, JS
  • Gupte, N
  • Balagopal, A
  • Asmuth, D
  • Hakim, J
  • Santos, B
  • Riviere, C
  • Hosseinipour, M
  • Sugandhavesa, P
  • Infante, R
  • Pillay, S
  • Cardoso, SW
  • Mwelase, N
  • Pawar, J
  • Berendes, S
  • Kumarasamy, N
  • Andrade, BB
  • Campbell, TB
  • Currier, JS
  • Cohn, SE
  • Gupta, A
  • et al.
Abstract

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Background: Women progress to death at the same rate as men despite lower plasma HIV RNA (viral load). We investigated sexspecific differences in immune activation and inflammation as a potential explanation. Methods: Inflammatory and immune activation markers [interferon-γ, tumor necrosis factor (TNF) α, IL-6, IL-18, IFN-γ- induced protein 10, C-reactive protein (CRP), lipopolysaccharide, and sCD14] were measured at weeks 0, 24, and 48 after combination antiretroviral therapy (cART) in a random subcohort (n = 215) who achieved virologic suppression in ACTG A5175 (Prospective Evaluation of Antiretrovirals in Resource-Limited Settings). Association between sex and changes in markers postcART was examined using random effects models. Average marker differences and 95% confidence intervals were estimated using multivariable models. Results: At baseline, women had lower median log10viral load (4.93 vs 5.18 copies per milliliter, P = 0.01), CRP (2.32 vs 4.62 mg/L, P = 0.01), detectable lipopolysaccharide (39% vs 55%, P = 0.04), and sCD14 (1.9 vs 2.3 μg/mL, P = 0.06) vs men. By week 48, women had higher interferon -γ (22.4 vs 14.9 pg/mL, P = 0.05), TNF-α (11.5 vs 9.5 pg/mL, P = 0.02), and CD4 (373 vs 323 cells per cubic millimeter, P = 0.02). In multivariate analysis, women had greater increases in CD4 and TNF-α but less of a decrease in CRP and sCD14 compared with men. Conclusions: With cART-induced viral suppression, women have less reduction in key markers of inflammation and immune activation compared with men. Future studies should investigate the impact of these sex-specific differences on morbidity and mortality.

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