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

Jyoti S. Mathad*, Nikhil Gupte, Ashwin Balagopal, David Asmuth, James Hakim, Breno Santos, Cynthia Riviere, Mina Hosseinipour, Patcharaphan Sugandhavesa, Rosa Infante, Sandy Pillay, Sandra W. Cardoso, Noluthando Mwelase, MBCHB, Jyoti Pawar, Sima Berendes, Nagalingeswaran Kumarasamy, Bruno B. Andrade, Thomas B. Campbell, Judith S. CurrierSusan E. Cohn, Amita Gupta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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 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.

Original languageEnglish (US)
Pages (from-to)123-129
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number2
StatePublished - Oct 1 2016


  • Antiretroviral treatment
  • HIV
  • Immune activation
  • Inflammation
  • Sex
  • Women

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)


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