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CD4/CD8 Ratio Better in HIV+ Women Than Men, But Survival Similar
  6th International Workshop on HIV and Aging
October 5-6, 2015, Washington, DC
Mark Mascolini
HIV-positive women in a 2000-person US cohort had a consistently higher (better) CD4/CD8 ratio than men when young, middle-aged, or older [1]. But this apparent immunologic advantage among women did not confer a survival benefit. Study results also suggested that a low CD4/CD8 ratio may predict mortality in HIV-positive people under 40, but not in older patients.
Vanderbilt University researchers who conducted this study noted that a lower CD4/CD8 ratio predicts death independently of age in HIV-negative adults. The CD4/CD8 ratio tends to fall with age in the general population as CD8-cell populations expand. In people with HIV, the researchers added, the CD4/CD8 ratio is a marker of immunosenescence and is linked to noncommunicable diseases. The ratio differs between women and men with and without HIV. The Vanderbilt team performed this analysis to determine whether sex differences in the CD4/CD8 ratio affect mortality risk as HIV-positive adults age.
The study involved 1554 men and 452 women who began care at the Vanderbilt Comprehensive Care Clinic between January 1998 and December 2012. All had two provider visits in the first year of care, and all had an undetectable viral load for at least 1 year on antiretroviral therapy (ART). Researchers compared baseline CD4/CD8 ratios in women and men in three age groups--young (under 40), middle-aged (40 to 49), and older (50 and up). They used Cox proportional hazard models to analyze associations between CD4/CD8 ratio and mortality stratified by age.
Women were significantly younger than men (median 40 versus 42, P = 0.004) and included a higher proportion of nonwhites (62% versus 38%, P < 0.001). Median initial CD4/CD8 ratio proved significantly higher in women than men (0.67 versus 0.54, P < 0.001), reflecting both a higher CD4 count and a lower CD8 count in women. Median CD4/CD8 ratio proved significantly higher (better) in women than men in every age group: young (n = 880) 0.71 versus 0.62, middle-aged (n = 763) 0.65 versus 0.51, and older (n = 363) 0.61 versus 0.44 (P < 0.001 for all comparisons).
Among study participants younger than 40, women had a significantly higher median CD4 count than men (555 versus 475, P < 0.01) but did not differ in CD8 count. Among participants 50 and older, women had a significantly lower median CD8 counts than men (722 versus 912, P < 0.01) but did not differ in CD4 count.
Through a median follow-up of 3.6 years, 129 of the 2006 participants (6.4%) died. Age-stratified analysis linked a low CD4/CD8 ratio to higher mortality risk only in people under 40 years old. After adjustment for sex and CD4 count, every 0.1-unit higher CD4/CD8 ratio cut the death risk 14% (adjusted hazard ratio 0.86), but that association stopped short of statistical significance (95% confidence interval 0.74 to 1.02, P = 0.08). In people older than 40, neither unadjusted nor adjusted models linked CD4/CD8 ratio to mortality.
The researchers proposed a low CD4/CD8 ratio "may be predictive of mortality in the youngest HIV-infected adults, even after adjusting for CD4 cell count."
A recent US-Spanish study of 95 people who reached a CD4 count above 500 on ART found that those with a persistently low CD4/CD8 ratio ran a higher risk of heightened CD8-cell activation and non-AIDS morbidity and mortality [2]. The authors proposed that "the CD4/CD8 ratio might help to further discriminate the risk of disease progression of successfully treated HIV-infected individuals, and a successful response to ART may require both normalization of the peripheral CD4+ T cell count and the ratio of CD4+ to CD8+ T cell counts."
1. Castilho JL, Shepherd BE, Koethe J, et al. Differences in associations of CD4/CD8 ratio, sex, and age on risk of mortality in HIV-infected adults on ART. 6th International Workshop on HIV and Aging. October 5-6, 2015, Washington, DC. Abstract 16.
2. Serrano-Villar S, Sainz T, Lee SA, et al. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality. PLoS Pathog. 2014;10:e1004078. http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004078