Immune reconstitution in older HIV-positive individuals

Kalayjian and colleagues from the ACTG presented clinically important findings from ACTG protocol 5015 at the Retrovirus Conference. [1] Older age has been known to be a predictor of accelerated HIV-disease progression, regardless of whether or not a patient is treated with HAART. However this could be due to various epidemiological factors in older individuals with HIV infection.

ACTG 5015 directly compared the virological and immunological responses to a single, standardised antiretroviral regimen in two age-defined cohorts treated at multiple clinics across the US. Antiretroviral therapy-naive subjects either older than 45 years or younger than 30 years with HIV-RNA >2000 copies/ml and CD4 <600 cells/mL were treated with lopinavir/ritonavir, d4T and FTC. Forty-five older (median age 50; range 45-79 yrs) and 45 younger (median 26; 18-30 yrs) subjects with similar demographic characteristics were enrolled.

At baseline viral loads were similar, while the older group had lower CD4 counts (155 vs 287; p=0.029), naive CD4 numbers (37 vs 105; p <0.001), and naive CD8 numbers (125 vs 185; p=0.030). After 48 weeks of therapy, HIV-RNA was suppressed to <50 copies/ml with equal frequency in the two groups (73% of older subjects vs. 67% of younger). Although there were a few more episodes of grade three or four toxicity, the onset of lipodystrophy or diabetes, or death in the older group, there were too few observations to reach statistical significance.

Changes in absolute CD4 counts, CD4%, CD8 counts and CD8% were not different in the two groups. However, the older group gained fewer naive CD4 cells (47 vs. 85; p=0.028) and the rise in naive CD8% was lower (9 vs. 13; p=0.019). The increase in naive CD8 cells was also lower, but did not achieve statistical significance. Data on thymic size also suggested that thymic mass increased to a lesser extent in older subjects.

These findings may weigh in the mind of the clinician when a decision to withhold or begin therapy in an older HIV-positive patient is being made. More toxicities and deaths were observed in the older cohort, although a larger or longer study would be needed to make this a significant finding. Although many of these events are likely drug-induced, the choice of withholding therapy in late stage disease is also unattractive. Therefore in HIV-positive individuals >45 years old, both increased disease progression, poorer immune reconstitution, and possibly poorer tolerance for therapy in late disease could encourage the earlier initiation of HAART.