Immunologic and Clinical Responses to HAART in Patients Over 50 Years of Age

The introduction of HAART has significantly improved the length of survival and the morbidity of HIV-infected patients through the improvement of the immunodeficiency caused by HIV infection.

Most published data on immunologic and clinical responses to HAART concern relatively young patients (median age, 35 to 40 years). Indeed, the HIV pandemic has mainly concerned young adults, and older patients tend to be excluded from clinical trials because of the risk of age-related co-morbidity.

Clinicians are now seeing an increasing number of older HIV-seropositive patients in their everyday practice. A recent report from the US Centers for Disease Control and Prevention (CDC) indicates that the cumulative number of AIDS cases in adults over 50 years quintupled during the previous decade.

This trend is likely to become more pronounced as HIV infection becomes a quasi-chronic disease in wealthy countries, and as the HIV-infected population ages as a consequence of effective treatment.

Only few data specifically concerning older HIV-infected populations have been published since the advent of HAART. The most recent studies of responses to HAART among older patients mainly involved small populations and limited follow-up.

Moreover, there is evidence that thymus involution in adults may negatively influence CD4 cell recovery, potentially leading to a lesser immunologic response to antiretroviral therapy and a higher risk of clinical progression than in younger subjects.

In the present study, researchers compared the immunologic and clinical responses to first-line HAART according to age (< and > or = 50 years) in a large cohort of 3015 HIV-infected patients followed for a median period of 30 months.

This prospective cohort study included 68 hospitals in France. A total of 3015 antiretroviral-naive patients, 401 of whom were aged 50 years or over, were enrolled following initiation of HAART.

The influence of age on the mean CD4 cell count increase on HAART was studied by using a two-slope mixed model. Progression, defined by the occurrence of a new AIDS-defining event (ADE) or death, was studied by Cox multivariate analyses.

Results

Among patients with baseline HIV RNA above 5 log copies/ml, CD4 mean increase during the first 6 months on HAART was +42.9 x 106 cells/l per month in patients under 50 years and +36.9 x 106 cells/l per month in patients over 50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9 and +15.6 x 106 cells/l per month (P < 0.0001).

Similar trends were observed in patients with baseline HIV RNA below 5-log copies/ml, and also after stratification for the baseline CD4 cell count.

After a median follow-up of 31.5 months, 263 patients had a new ADE and 44 patients died. After adjustment for baseline characteristics, older patients had a significantly higher risk of clinical and were more likely to achieve a viral load below 500 copies/ml.

Conclusion

Patients over 50 years of age have an immunologic response to HAART. However, their CD4 cell reconstitution is significantly slower than in younger patients, despite a better virologic response. This impaired immunologic response may explain their higher risk of clinical progression.

Discussion

One of the striking differences between the older group and the younger one is that the older patients were at a much more advanced stage of HIV disease than the younger patients, both at inclusion in this study and at FHDH enrollment.

Moreover, the distribution of HIV transmission categories was quite particular in the older group. About half these patients (46.6%) were heterosexuals, very few were intravenous drug users (0.3 versus 13.7% of younger patients) and the HIV transmission group was frequently unknown (16.5 versus 7.9%).

We found that older age was associated with a better virological response to HAART. This confirms previous reports that younger age is associated with weaker virological responses and with viral rebound. Whether this effect is due to poorer adherence or to less favorable pharmacokinetics in younger patients remains to be determined.

Despite the better virologic response in older subjects, the researchers found that the immunologic response to HAART (CD4 cell count increment) was weaker than in younger subjects. Previous studies involving far fewer patients and non-longitudinal methods failed to show such a difference.

The CD4 cell count increment according to the baseline viral load level was slower in older patients than in younger patients and, as expected, was more rapid during the first 6 months of HAART than subsequently, regardless of age. These findings were not influenced by the baseline CD4 cell count (< 200 or ≥ 200 × 10⁶ cells/l).

The slower CD4 cell reconstitution in older patients may be related to an impaired thymic function. CD4 reconstitution has been shown to be age dependent.

There are currently no specific clinical guidelines on HIV-infected patients over 50 years of age. Whether this slower immune response in older patients should have implications in the clinical management of elderly patients notably for the timing of HAART initiation, remain to be assessed after evaluating the relative contribution of age-related immune function on one hand, and late diagnosis and treatment on the other.

Older patients had a faster clinical progression to a new ADE or to death, as well as a faster progression to a new ADE regardless of death, than younger patients.

The higher incidence of opportunistic infections in older patients was probably related to the poorer immunologic status and response to HAART of these subjects as it could not be related to an impaired virologic response.

In conclusion, the authors write, “Patients over 50 years of age do exhibit an immune response after HAART. However, relative to younger patients, their CD4 cells reconstitution is significantly slower, despite a better virological response. This may explain why older patients have a higher risk of clinical progression on HAART.”

“Awareness campaigns targeting patients in this age group, and their practitioners, are needed to reduce the current delay in HIV diagnosis and treatment and thereby, preserving their chance of treatment success.”

10/13/04

Reference
S Grabar and others. Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV. AIDS 18(15): 2029-2038, October 21, 2004.