Objective: 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, we compared the viral and immune responses to a uniform antiretroviral regimen according to age.

Methods: Multi-center, prospective treatment trial of older (³45 yrs) and younger (£30 yrs) HIV-infected antiretroviral therapy-naïve 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.

Results: 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 log₁₀HIV-RNA: 4.81 vs 4.45 (p = 0.083); CD4 counts 155 vs 287 (p = 0.029); naïve CD4 counts 37 vs 105 (p < 0.001); and naïve CD8counts 125 vs 185 (p = 0.030). 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 (p = 0.628). Median changes (and IQR) from baseline to wk 48 in T-cells were:

 

	Older, n = 41		Younger, n = 39		p-values
DCD4 counts	155	(92,264)	188	(109,300)	—
DCD4%	9	(5,13)	8	(5,12)	—
DNaïve CD4 counts	47	(18, 86)	85	(44,139)	0.028
DNaive CD4 %	3	(-3, 8)	3	(-3,12)	—
DCD8 counts	22	(-198, 296)	-1	(-227, 167)	—
DCD8%	-11	(-17, -6)	-10	(-16, -4)	—
DNaïve CD8 counts	56	(11, 128)	102	(53, 170)	—
DNaïve CD8%	9	(2, 12)	13	(8, 20)	0.019

 

There were no differences between the groups in changes, from baseline to wk 48, in other T-cell phenotypes. Toxicities, adverse events and additional functional immune indices will be described in more detail.

Conclusion: Despite similar virologic responses, older HIV-infected subjects had reduced naïve T-cell restoration with antiretroviral therapy. A diminished potential for naïve cell reconstitution may contribute to the heightened, age-related morbidity and mortality in HIV-disease.