Response to highly active antiretroviral therapy in HIV-infected patients aged 60 years or older after 24 months follow-up

The study of elderly persons with HIV disease is of interest for two reasons: the low prevalence of AIDS in individuals aged 60 years or older [1], and the fact that epidemiological evidence has mostly been collected before the introduction of highly active antiretroviral therapy (HAART) [2]. It seems that an aggressive therapeutic approach is warranted for older patients with HIV disease [3]. We compared the response to first-line HAART in patients aged 60 years or older and patients aged 40 years or less. The virological and immunological response to first-line HAART containing two nucleoside analogues and a protease inhibitor was prospectively evaluated in a cohort of 842 patients who initiated treatment between 1997 and 1998 at Hospital del Mar, in Barcelona, Spain. After 24 months follow-up, findings in 28 (3.3% patients aged 60 years or older were compared with those in 671 patients aged 40 years or less. Data were registered using a standardized form, and included the following variables: age and sex; disease stage; risk factors for HIV infection; date of treatment initiation; CD4 T cell count; HIV-1-RNA quantitation (NASBA Ultrasensitive, Organon Teknika, IGEN Inc., Rockville, USA) (minimum detectable levels 50 copies/ml); previous antiretroviral treatment; and drugs administered. Assessments at follow-up included adherence to HAART, adverse events, CD4 T cell count, viral load, and mortality rates. The hospital pharmacist in charge of the delivery of antiretroviral drugs checked adherence using a computer-assisted pharmacy dispensing system. Adherence was assessed by self-report, asking how many doses had been missed in the month before the visit and by pharmacy appointment count. Adverse drug reactions were graded 3 or 4 according to the WHO classification. The baseline characteristics of the two groups of patients are shown in Table 1. No differences were found with regard to sex, percentage of naive cases, expected potency of HAART regimen containing either indinavir (75%), nelfinavir (15% or ritonavir (10%), as well as the median plasma viral load and the median CD4 lymphocyte cell count. The only variable difference in the two groups of patients was the higher prevalence of sexually transmitted HIV in the older patients. In comparison with patients aged 40 years or less, those aged 60 years or older showed a trend towards better adherence to medication and a more favourable virological and immunological outcome; the differences were, however, not statistically significant. Adverse events were significantly more frequent in the elderly group (Table 1). After 24 months follow-up, only 10 (36% elderly patients continued therapy with protease inhibitor-containing HAART, the remaining patients were switched to non-analogue nucleosides. Self-reported lipodystrophy was found in 63% (14/22) of older patients compared with 33% (180/541) in patients aged 40 years or less (P = 0.003, odds ratio 3.5, 95% confidence interval 3.5–9.33). Three elderly patients died as a result of HIV infection (n = 1), suicide (n = 1), and respiratory failure (n = 1).Table 1: Baseline characteristics and outcome of HIV-infected patients treated with highly active antiretroviral therapy (protease inhibitor plus two nucleoside reverse transcriptase inhibitors) after 24 months of follow-up in patients aged 60 years or older compared with that of control subjects aged 40 years or younger. Numerous studies conducted before the HAART era have shown that older individuals have a more severe HIV disease course and a shorter survival rate [4,5], probably in relation to the presence of underlying conditions [6], physiological decline in the competence of the immune system associated with ageing, and late diagnosis of HIV infection [2,7]. It has been found that age is not related to HAART outcome [8]; however, the access to antiretroviral therapy was the only predictor of survival in a cohort of patients aged 50 years or older [9]. A recent case–control study [3], in which the outcome in 21 patients aged 55 years or older was compared with 84 patients aged 35 years or younger, all treated with HAART, concluded that the virological outcome was not essentially different in both groups but the immunological response appeared to be blunted among older patients. We have not found significant differences in the virological and immunological outcomes between the two groups of patients. It should be noted, however, that there was a trend towards a more favourable clinical course in older patients, which may be explained by a better adherence to the HAART regimen. The high frequency of adverse events in older patients may be related to an age-related impairment of renal and liver function as well as decreased serum albumin levels. On the other hand, the high rate of lipodystrophy may be a confounding factor associated with the ageing process. In prospective cohort studies [10], age has been recognized as a risk factor for developing the syndrome. In the present study, the virological and immunological response to HAART after a 24 month follow-up was not influenced by the patient's age. Individuals aged 60 years or older, however, experienced a significantly higher rate of adverse events than patients aged 40 years or less. More research is needed concerning treatment options other than HAART for HIV-infected patients with advanced age. Hernando Knobela Ana Guelara Gabriel Valldecilloa Alexia Carmonab Alicia Gonzáleza José L. López-Colomésa Pedro Saballsa Juan L. Gimenoa Adolfo Díeza