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Older Age is Associated with Reduced Naive T-cell Responses to Antiretroviral Therapy: 48-week Results of ACTG Protocol 5015
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Older age is a strong predictor of accelerated HIV-disease progression, both in the presence and in the absence of HAART. To identify potential immune correlates of this interaction, ACTG researchers compared the viral and immune responses to a uniform antiretroviral regimen according to age.
This is a multi-center, prospective treatment trial of older (>45 yrs) and younger (<30 yrs) HIV-infected antiretroviral therapy-naive subjects, with HIV-RNA > 2000 copies/ml and CD4 < 600 cells/mL.
All subjects received lopinavir/ritonavir, d4T and FTC. Comparisons of changes from baseline to wk 48 in HIV-RNA and T-cells by "intent-to-treat" analysis using Wilcoxon rank sum test.
Forty-five (45) older (median age 50; range 45-79 yrs) and 45 younger (median 26; 18-30 yrs) subjects with similar demographic characteristics were enrolled.
Baseline median values for older vs younger subjects were 4.81 log (64,000 copies/ml) vs 4.45 log (28,000 copies/ml), not much different; CD4 counts 155 vs 287; naive CD4 counts 37 vs 105 (p < 0.001); and naive CD8counts 125 vs 185.
At 48 wks, HIV-RNA < 50 copies/ml was found in 30 of 41 (73%) older subjects compared with 26 of 39 (67%) younger subjects, no significant difference. Median changes from baseline to wk 48 in T-cells were:
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The authors concluded that despite similar virologic responses, older HIV-infected subjects had reduced naive T-cell restoration with antiretroviral
therapy. A diminished potential for naive cell reconstitution may contribute to the heightened, age-related morbidity and mortality in HIV-disease.
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