 |
|
|
| |
Immune Reconstitution in Older HIV+ Individuals
Written by David Margolis, MD, University of Texas, Southwestern Medical Center
|
| |
| |
Kalayjian and colleagues from the ACTG presented clinically important findings from ACTG protocol 5015 (abstr. 346) at the Retrovirus Conference (Feb 10-14, 2003). 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 immune responses to a single, standardized antiretroviral regimen in 2 age cohorts treated at multiple clinics across the US. Antiretroviral therapy-naive subjects either older than 45 yrears 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 counts (37 vs 105; p < 0.001), and naive CD8 counts (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 3 or 4 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-infected 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-infected 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.
|
|
| |
|
|
|
|
|
