OBJECTIVE: Despite lower plasma HIV RNA levels, women progress faster to AIDS than men. The reasons for these differences are not clear but might be a consequence of an elevated inflammatory response in women. METHODS: We investigated sex differences in cytokine profiles by measuring the concentrations of 36 cytokines/chemokines by Luminex in blood of women and men (sex at birth) with chronic HIV infection under suppressive therapy. We initially performed a principal component analysis to see if participants clustered by sex, and then fit a partial least squares discriminant analysis (PLS-DA) model where we used cytokines to predict sex at birth. The significance of the difference in nine cytokines with VIP greater than 1 was tested using Wilcoxon test-rank. Further, potential confounding factors were tested by multivariate linear regression models. RESULTS: Overall, we predicted sex at birth in the PLS-DA model with an error rate of approximately 13%. We identified five cytokines, which were significantly higher in women compared with men, namely the pro-inflammatory chemokines CXCL1 (Gro-α), CCL5 (RANTES), CCL3 (MIP-1α), CCL4 (MIP-1β), as well as the T-cell homeostatic factor IL-7. The effect of sex remained significant after adjusting for CD4 + , age, ethnicity, and race for all cytokines, except for CCL3 and race. CONCLUSION: The observed sex-based differences in cytokines might contribute to higher immune activation in women compared with men despite suppressive therapy. Increased levels of IL-7 in women suggest that homeostatic proliferation may have a differential contribution to HIV reservoir maintenance in female and male individuals. Our study emphasizes the importance of sex-specific studies of viral pathogenesis.
OBJECTIVE: Despite lower plasma HIV RNA levels, women progress faster to AIDS than men. The reasons for these differences are not clear but might be a consequence of an elevated inflammatory response in women. METHODS: We investigated sex differences in cytokine profiles by measuring the concentrations of 36 cytokines/chemokines by Luminex in blood of women and men (sex at birth) with chronic HIV infection under suppressive therapy. We initially performed a principal component analysis to see if participants clustered by sex, and then fit a partial least squares discriminant analysis (PLS-DA) model where we used cytokines to predict sex at birth. The significance of the difference in nine cytokines with VIP greater than 1 was tested using Wilcoxon test-rank. Further, potential confounding factors were tested by multivariate linear regression models. RESULTS: Overall, we predicted sex at birth in the PLS-DA model with an error rate of approximately 13%. We identified five cytokines, which were significantly higher in women compared with men, namely the pro-inflammatory chemokines CXCL1 (Gro-α), CCL5 (RANTES), CCL3 (MIP-1α), CCL4 (MIP-1β), as well as the T-cell homeostatic factor IL-7. The effect of sex remained significant after adjusting for CD4 + , age, ethnicity, and race for all cytokines, except for CCL3 and race. CONCLUSION: The observed sex-based differences in cytokines might contribute to higher immune activation in women compared with men despite suppressive therapy. Increased levels of IL-7 in women suggest that homeostatic proliferation may have a differential contribution to HIV reservoir maintenance in female and male individuals. Our study emphasizes the importance of sex-specific studies of viral pathogenesis.
Authors: Theodore D Ruel; Brian C Zanoni; Isaac Ssewanyana; Huyen Cao; Diane V Havlir; Moses Kamya; Jane Achan; Edwin D Charlebois; Margaret E Feeney Journal: Clin Infect Dis Date: 2011-08-12 Impact factor: 9.079
Authors: J S Evans; T Nims; J Cooley; W Bradley; L Jagodzinski; S Zhou; G P Melcher; D S Burke; M Vahey Journal: J Infect Dis Date: 1997-04 Impact factor: 5.226
Authors: Angela Meier; J Judy Chang; Ellen S Chan; Richard B Pollard; Harlyn K Sidhu; Smita Kulkarni; Tom Fang Wen; Robert J Lindsay; Liliana Orellana; Donna Mildvan; Suzane Bazner; Hendrik Streeck; Galit Alter; Jeffrey D Lifson; Mary Carrington; Ronald J Bosch; Gregory K Robbins; Marcus Altfeld Journal: Nat Med Date: 2009-07-13 Impact factor: 53.440
Authors: Jeffy George; Ryan C Johnson; Mary J Mattapallil; Lynnsey Renn; Ronald Rabin; D Scott Merrell; Joseph J Mattapallil Journal: PLoS One Date: 2019-09-06 Impact factor: 3.240