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CD4 Changes on Effective ART Similar in People Under and Over 50 Years Old
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2nd International Workshop on HIV and Aging, October 27-28, 2011, Baltimore, Maryland
Mark Mascolini
Adding to the growing mound of (conflicting) evidence on how age affects CD4 changes in people on suppressive antiretroviral therapy (ART), Canadian researchers reported no difference in rate of CD4 recovery, rate of CD4/CD8 ratio recovery, proportions gaining at least 100 CD4s, and proportions reaching at least 350 CD4s when comparing people under and over 50 years old [1].
McGill University and University of Montreal investigators cited seven studies that found no CD4 recovery difference with age and nine studies that did find such a difference. To assess CD4 changes in their own patient population, these researchers focused on 41 people with a low pretreatment CD4 count and continuous virologic suppression for 5 or more years. The study excluded people with more than one viral load blip. Twenty-five people were younger than 50, and 16 people were 50 or older.
Age averaged 57 (range 52 to 60) in the older group and 36 (range 33 to 41) in the younger group. Fifteen of the 16 older people were men, as were 20 of the 25 younger people. Average pretreatment CD4 count was low in both groups but nonsignificantly higher in the older people (93 versus 84). Pretreatment CD4/CD8 ratios were similar in the older group (0.13) and the younger group (0.11), as were pretreatment viral loads (4.5 and 4.4 log, or about 30,000 and 25,000 copies).
Most people in both groups (81% of the older people and 84% of the younger) began treatment with a ritonavir-boosted protease inhibitor. Time to first undetectable viral load was faster in the older group (0.6 versus 1.1 years), but that difference was not statistically significant.
People over and under 50 gained virtually the same number of CD4 cells per year over 5 years, averaging 36.38 +/- 11.67 cells per year in the older group and 37.86 +/- 5.28 cells per year in the younger group (P = 0.91). Change in the CD4/CD8 ratio was nearly identical in the two groups, averaging 0.060 +/- 0.004 per year in the older group and 0.064 +/- 0.002 per year in the younger group (P = 0.44).
Proportions of people who gained at least 100 CD4s after 5 years of follow-up were 67% in the older group and 62% in the younger group. The proportion who reached a CD4 count above 350 was lower in older people than younger people (50% versus 67%), but that difference lacked statistical significance. If those proportions held in a large population, though, half versus two thirds getting their CD4 count over 350 might reach statistical (and clinical) significance. Not reaching 350 CD4s after 5 years could indicate a slower flow of recent thymic immigrants in the older group [2].
Julian Falutz, the senior author of this study, observed several times during the Aging Workshop that 50 years is an arbitrary cutoff for older versus younger people that is widely applied in studies of people with HIV but may be physiologically meaningless. He and others proposed that 60 years may be a more telling cutoff, but they recognize that most HIV cohorts include too few people over 60 (at this point) to make over-versus-under 60 comparisons meaningful.
At least year's Aging Workshop, a 44,491-person US-Canadian study found that people over 50 consistently entered HIV care with a lower CD4 count than younger people [3]. Older people did seem to close the CD4 gap with younger people after they entered care: In an analysis adjusted for age, race, HIV transmission group, and cohort, estimated average annual increase in CD4 count at presentation rose by 7 cells (95% confidence interval 5 to 9) in the 50-and-over group and by 5 cells (95% confidence interval 4 to 6) in people under 50. From 1997 through 2007, the proportion of people 50 or over entering care rose significantly from 17% to 27% (P < 0.01).
References
1. Ndumbi P, Tsoukas C, Chilakos J, Falutz J. Recovery of CD4 T-cells in older versus younger patients with prolonged virologic suppression and low baseline CD4 T-cell counts. 2nd International Workshop on HIV and Aging, October 27-28, 2011. Baltimore, Maryland. Abstract P_16.
2. Li T, Wu N, Dai Y, et al. Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy. Clin Infect Dis. 2011;53:944-951.
3. Althoff KN, Gebo KA, Gange SJ, et al; North American AIDS Cohort Collaboration on Research and Design. CD4 count at presentation for HIV care in the United States and Canada: are those over 50 years more likely to have a delayed presentation? AIDS Res Ther. 2010;7:45. http://www.aidsrestherapy.com/content/7/1/45.
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