Immunologic and Clinical Responses to Highly Active
Immunologic and Clinical Responses to Highly Active
Objective: To study immunologic and clinical responses to HAART in patients over 50 years old.
Design and Methods: A prospective cohort study which 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 × 10 cells/l per month in patients under 50 years and +36.9 × 10 cells/l per month in patients over 50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9 and +15.6 × 10 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 progression (hazard ratio (HR) = 1.52 [95% confidence interval (CI), 1.15-2.00]) and were more likely to achieve a viral load below 500 copies/ml [HR = 1.23, (95% CI, 1.11-1.38)].
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.
The introduction of highly active antiretroviral therapy (HAART) has markedly improved the length of survival and the morbidity of HIV-infected patients through the improvement of the immunodeficiency caused by the 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 comorbidity.
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 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, we compared the immunologic and clinical responses to first-line HAART according to age (< and ≥ 50 years) in a large cohort of 3015 HIV-infected patients followed for a median period of 30 months.
Objective: To study immunologic and clinical responses to HAART in patients over 50 years old.
Design and Methods: A prospective cohort study which 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 × 10 cells/l per month in patients under 50 years and +36.9 × 10 cells/l per month in patients over 50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9 and +15.6 × 10 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 progression (hazard ratio (HR) = 1.52 [95% confidence interval (CI), 1.15-2.00]) and were more likely to achieve a viral load below 500 copies/ml [HR = 1.23, (95% CI, 1.11-1.38)].
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.
The introduction of highly active antiretroviral therapy (HAART) has markedly improved the length of survival and the morbidity of HIV-infected patients through the improvement of the immunodeficiency caused by the 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 comorbidity.
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 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, we compared the immunologic and clinical responses to first-line HAART according to age (< and ≥ 50 years) in a large cohort of 3015 HIV-infected patients followed for a median period of 30 months.