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Sex-related Inflammatory Marker Changes Pre and Post
Antiretroviral Treatment (ART) Initiation
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Reported by Jules Levin
CROI 2014 March 3-6 Boston, MA
JS Mathad1, N Gupte2, A Balagopal3, D Asmuth4, J Hakim5, N Kumarasamy6, T Campbell7, JS Currier8, SE Cohn9, A Gupta2,3for the NWCS319 and ACTG 5175 study teams
1Weill Cornell Medical College, New York, NY, USA 2Johns Hopkins University-ByramjeeJeejeebhoyMedical College Clinical Trials Unit, Pune, India 3Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4University of California Davis Medical Center, Sacramento, CA, USA, 5University of Zimbabwe College of Health Sciences, Harare, Zimbabwe, 6YRGCARE Medical Centre, Chennai, India, 7University of Colorado-Denver, Aurora, CO, USA, 8David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA, 9Northwestern University Feinberg School of Medicine, Chicago, IL, USA
"Post-ART increases in markers such as CRP, LPS, and sCD14 (inflammation/activation markers) in women may reflect an ongoing sex-related inflammatory response and explain why women progress to AIDS with lower viral loads."
"Before ART, women had a more favorable immune profile with significantly higher CD4 and lower VL, CRP, detectable LPS and sCD14 than men. With ART, though, men experienced more of a decrease in inflammatory markers than women, erasing women's initial advantage. This difference in response may explain why women progress to AIDS with lower viral loads. Further studies should investigate sex-specific differences in immune activation/inflammation pathways."
Program Abstract-
Background: Immune activation and inflammation are associated with HIV disease progression
and death. Women, on average, have lower plasma HIV RNA (VL) early in infection but progress
to AIDS at the same rate as men. Sex-specific differences in immune activation/inflammation
pre- and post-ART initiation could explain these observed clinical differences,
but this has not been well studied.
Methodology: Inflammatory/immune activation markers (IFN-γ, TNF-α, IL-6, IL-18, IP-10, CRP, LPS, sCD14,
EndoCAb IgM, activated CD4/CD8) were measured pre-ART and at week 24 and 48 post-ART on a
random sub-cohort from ACTG A5175 (PEARLS) comparing 3 ART regimens in 9 countries. Only
those virologically suppressed on ART were included. We did a within-sex comparison of median
marker levels between week 48 and baseline. Percent detection was used for LPS as many had
no detectable LPS. To understand if women had more or less change in markers over time vs men,
we performed multivariable longitudinal random effects modeling adjusting for age, country, BMI,
baseline CD4, log10 VL, hemoglobin (Hb) and randomized ART arm.
Results: Samples were available for 125 men and 121 women. Women were younger (33 vs 36 years,
p=0.01) and included more black subjects (64% vs 43%, p<0.001). At baseline pre-ART,
women had higher median CD4 counts (195 vs 165 cells/mm3, p=0.01) and lower median VL
(4.9 vs 5.1 log10 copies/mL, p=0.01) and Hb (11 vs 13 g/dL, p<0.001) than men. Women also had lower median
CRP (2.1 vs 4.8 mg/L, p=0.002), percent detectable LPS (36% vs 53%, p=0.01), median sCD14 (1.8 vs 2.3 log10
pg/mL, p=0.009), and higher median EndoCAb (52 vs 45 MMU/mL, p=0.04) than men.
At week 48, women had higher median IFN-γ (21 vs 13 pg/mL, p=0.04) compared to men.
Compared to baseline, men had lower levels of all inflammatory markers at week 48, except percent
detectable LPS. Women also had decreases in TNF-α, IL-18 and IP-10, but had no change in IFN-γ, IL-6,
and increased percent detectable LPS. In multivariate longitudinal analyses of changes over 48 weeks,
women on average had a greater slope change in CD4 of 40 cells/mm3 (CI: 17-63, p=0.001),
TNF-α of 3.3 ng/mL (CI: 0.16-6.5, p=0.04), but less of change in VL (0.31 log copies/mL, CI: 0.11-0.52,
p=0.003), CRP (8 mg/L, CI: 2.4-13, p=0.005) and log10 sCD14 (3.8 log10 ng/mL, CI: 1.8-5.8, p<0.001)
as compared to men.
Conclusions: Before ART, women had a more favorable immune profile with significantly higher CD4
and lower VL, CRP, detectable LPS and sCD14 than men. With ART, though, men experienced
more of a decrease in inflammatory markers than women, erasing women's initial advantage.
This difference in response may explain why women progress to AIDS with lower viral loads.
Further studies should investigate sex-specific differences in immune activation/inflammation pathways.
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