Jyoti S Mathad1, 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, Jyoti Pawar, Sima Berendes, Nagalingeswaran Kumarasamy, Bruno B Andrade, Thomas B Campbell, Judith S Currier, Susan E Cohn, Amita Gupta. 1. *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; and ¶¶¶Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL.
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.
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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