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Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation
- 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
- et al.
Published Web Location
https://doi.org/10.1097/qai.0000000000001095Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.