Prior research has indicated that older HIV positive individuals tend to experience smaller CD4 cell gains after starting treatment, but past studies have produced mixed findings. Poor immune recovery may be due to age-related changes in the thymus and lymphoid tissues that produce T-cells or the cumulative effects of chronic inflammation and persistent immune activation.

To shed further light on this issue, Keri Althoff from Johns Hopkins University and colleagues performed a pooled analysis of medical records from participants in 19 prospective cohort studies that are part of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

The analysis included 12,196 treatment-naive patients who started combination antiretroviral therapy between 1998 and 2008. The average age was 42 years, and about 20% were age 50 or older. Overall, they had relatively advanced HIV disease, with CD4 counts below 250 cells/mm3; baseline CD4 counts did not differ according to age.

Nearly three-quarters started on an ART regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI), while the rest received a ritonavir-boosted protease inhibitor (PI). About half changed their regimen during the follow-up period (48% of NNRTI recipients and 57% of PI recipients).

The investigators looked at how long it took to reach HIV viral load < 500 copies/mL and how long to achieve a CD4 cell gain of at least 100 cells/mm3 within the first 2 years of treatment.

Results

People who started on a boosted PI were less likely to achieve a virological response, or viral load suppression (adjusted hazard odds ratio [HOR] 0.77, or 23% less likely). 

Patient age, however, did not have a significant influence on likelihood of viral suppression. 

Conversely, immunological response did not differ according to type of ART regimen. 

Here, however, increasing age was associated with decreasing likelihood of achieving a CD4 cell increase of 100 cells/mm3, regardless of initial regimen: 

< 30 years: reference group for comparison; 
30-39 years: adjusted HOR 0.92, or 8% less likely; 
40-49 years: adjusted HOR 0.85, or 15% less likely; 
50-59 years: adjusted HOR 0.82, or 18% less likely; 
> 60 years: adjusted HOR 0.74, or 26% less likely. 

Based on these findings, the study authors concluded, "We found no evidence of an interaction between age and initial antiretroviral regimen on virologic or immunologic response to [combination ART]."

"Decreased immunologic response with increasing age may have implications for age-specific when-to-start guidelines," they suggested.

"Our data do not currently support the use of specific [combination ART] regimens for specific age groups," they elaborated in their discussion. "However, given the impact of CD4 cell count on long-term survival, initiating [combination ART] at higher CD4 cell counts for older individuals may be useful given the decreased likelihood of a robust CD4 cell response with increasing age."

Investigator affiliations: Johns Hopkins University, Baltimore, MD; Yale University and the VA Connecticut Healthcare System, New Haven, CT; University of California, San Francisco, San Francisco, CA; University of Alabama, Birmingham, Birmingham, AL; Kaiser Permanente Northern California, Oakland, CA; University of Calgary, Calgary, Alberta, Canada; University of North Carolina, Chapel Hill, Chapel Hill, NC; Temple University, Philadelphia, PA; McGill University, Montreal, Quebec, Canada.

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