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Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation.

  • Author(s): Mathad, Jyoti S
  • Gupte, Nikhil
  • Balagopal, Ashwin
  • Asmuth, David
  • Hakim, James
  • Santos, Breno
  • Riviere, Cynthia
  • Hosseinipour, Mina
  • Sugandhavesa, Patcharaphan
  • Infante, Rosa
  • Pillay, Sandy
  • Cardoso, Sandra W
  • Mwelase, Noluthando
  • Pawar, Jyoti
  • Berendes, Sima
  • Kumarasamy, Nagalingeswaran
  • Andrade, Bruno B
  • Campbell, Thomas B
  • Currier, Judith S
  • Cohn, Susan E
  • Gupta, Amita
  • New Work Concept Sheet 319 and AIDS Clinical Trials Group A5175 (PEARLS) Study Teams
  • et al.
Abstract

BACKGROUND:Women progress to death at the same rate as men despite lower plasma HIV RNA (viral load). We investigated sex-specific 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 post-cART 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 log10 viral 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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