Sex-related Differences in Inflammatory and Immune Activation Markers before and after combined Antiretroviral Therapy Initiation.

TitleSex-related Differences in Inflammatory and Immune Activation Markers before and after combined Antiretroviral Therapy Initiation.
Publication TypeJournal Article
Year of Publication2016
AuthorsMathad 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
Corporate AuthorsNew Work Concept Sheet 319 and AIDS Clinical Trials Group A5175(PEARLS) study teams
JournalJ Acquir Immune Defic Syndr
Date Published2016 May 27
ISSN1944-7884
Abstract

BACKGROUND: Women progress to death at the same rate as men despite lower plasma HIV RNA (VL). We investigated sex-specific differences in immune activation and inflammation as a potential explanation.

METHODS: Inflammatory and immune activation markers (IFN-γ, TNF-α, IL-6, IL-18, IP-10, CRP, LPS, sCD14) were measured at weeks 0, 24, and 48 post-cART in a random subcohort (n=215) who achieved virologic suppression in ACTG A5175 (PEARLS). Association between sex and changes in markers post-cART was examined using random effects models. Average marker differences and 95%CI were estimated using multivariable models.

RESULTS: At baseline, women had lower median log10VL (4.93 vs 5.18 copies/mL, p=0.01), CRP (2.32 vs 4.62 mg/L, p=0.01), detectable LPS (39% vs 55%, p=0.04), and sCD14 (1.9 vs 2.3 mcg/mL, p=0.06) versus men. By week 48, women had higher IFN-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/mm, 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 to 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.

DOI10.1097/QAI.0000000000001095
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID27258230
Grant ListKL2 TR000458 / TR / NCATS NIH HHS / United States
P30 AI094189 / AI / NIAID NIH HHS / United States
R01 AI080417 / AI / NIAID NIH HHS / United States
U01 AI027668 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States