HIV disease and advanced age: an increasing therapeutic challenge

The mean age of patients at both first HIV detection and AIDS diagnosis is progressively rising over time. However, reliable epidemiological estimates, clinical data or controlled therapeutic and outcome figures are lacking for elderly patients, especially with regard to laboratory and clinical response to antiretroviral therapy, treatment tolerability, drug-drug interactions, short- and long-term toxicity, and interactions with underlying illnesses and concurrent pharmacological treatment. In fact, the large majority of randomised, controlled trials evaluating and comparing new antiretroviral drugs or anti-HIV therapeutic strategies, as well as antimicrobial treatment or chemoprophylaxis of HIV-related complications, either excluded patients with advanced age and/or concurrent disorders or did not offer substudies or detailed data analysis focusing on older patients compared with younger ones. The life expectancy of HIV-infected persons receiving highly active antiretroviral therapy (HAART) is now extended (approaching that of the general population), so that the definition of AIDS has lost its epidemiological and clinical significance thanks to the immune reconstitution resulting from potent antiretroviral therapy. However, an ever-increasing number of individuals aged > or =50 years with HIV infection is expected in the coming years, as a result of both increased survival of patients with treated disease and delayed recognition of individuals with occult HIV disease. The limited data available about combined antiretroviral therapy in the elderly seem to show an overlapping virological success rate but a slower and blunted immune recovery compared with younger patients. Thymic output, however, seems somewhat preserved even in adulthood and may contribute to the reconstitution of most of the quantitative and functional T cell abnormalities caused by HIV disease. More attention must be paid to underlying end-organ disorders, as well as expected pharmacological interactions and combined drug toxicity that may interfere with HAART efficacy and patients' compliance with recommended regimens and could lead to increased adverse effects. The available guidelines for antiretroviral treatment and therapy and prophylaxis of AIDS-related illnesses should be regularly updated and should include problems related to HIV disease in an aging population. Specific trials or substudies focusing on older people are warranted to obtain controlled data on all issues of antiretroviral therapy in the elderly, including time and mode of initiation, and modification and salvage HAART regimens. Antiretroviral drug dosage adjustment to take into account underlying pathological conditions or other pharmacological treatments is another emerging issue.