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

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Journal of Acquired Immune Deficiency Syndromes

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.

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; New Work Concept Sheet 319 and AIDS Clinical Trials Group A5175 (PEARLS) Study Teams. Sex-related differences in inflammatory and immune activation markers before and after combined antiretroviral therapy initiation. J Aquir Immune Defic Syndr. 2016 Oct 1;73(2):123-9.
Division of Infectious Diseases, Center for Global Health, Weill Cornell Medical College, New York, NY
Johns Hopkins Clinical Trials Unit, Byramjee Jeejeebhoy Government Medical College, Pune, India
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD
Division of Infectious Diseases, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA
Department of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
Division of Infectious Diseases, Hospital Nossa Senhora de Conceição, Porto Alegre, Brazil
Les Centres GHESKIO, Port-Au-Prince, Haiti
Department of Medicine, University of North Carolina-Lilongwe, Lilongwe, Malawi
Research Institute for Health Sciences, Chiang Mai, Thailand
Impacta Peru, San Miguel, Peru
Durban International Clinical Research Site, Durban University of Technology, Durban, South Africa
STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil
Department of Medicine, University of Witwatersrand, Johannesburg, South Africa
National AIDS Research Institute (ICMR), Pune, India
Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre, Malawi
YRGCARE Medical Center, Chennai, India
Investigative Medicine Branch, Laboratório Integrado de Microbiologia e Imunorregulação (LIMI), Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil
Division of Infectious Diseases, University of Colorado-Denver, Aurora, CO
Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL