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



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.



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.



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.
*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.
Jyoti S
JS
Mathad
Nikhil
N
Gupte
Ashwin
A
Balagopal
David
D
Asmuth
James
J
Hakim
Breno
B
Santos
Cynthia
C
Riviere
Mina
M
Hosseinipour
Patcharaphan
P
Sugandhavesa
Rosa
R
Infante
Sandy
S
Pillay
Sandra W
SW
Cardoso
Noluthando
N
Mwelase
Jyoti
J
Pawar
Sima
S
Berendes
Nagalingeswaran
N
Kumarasamy
Bruno B
BB
Andrade
Thomas B
TB
Campbell
Judith S
JS
Currier
Susan E
SE
Cohn
Amita
A
Gupta
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D012737:Sex Factors
D019380:Anti-HIV Agents; D015415:Biomarkers; D018836:Inflammation Mediators