Study of the Effect of Atorvastatin for Reducing "Inflaming" (Aging-related Complication) in HIV-infected Patients Older Than 45 Years Receiving a Protease Inhibitor-based Regimen Versus a Raltegravir-based Regimen

Physicians in charge of HIV-infected patients are increasingly being faced to previously unrecognized comorbid conditions such as atherosclerosis and cardiovascular events, loss of renal function, osteopenia/osteoporosis and bone fractures or non-AIDS-defining cancers (1-4).

The incidence of these conditions seems to be higher than in the general population but there are controversial data about if these diseases appear at a younger age in HIV-infected patients.

Different pathogenic mechanisms are involved in the increased risk of comorbidities. First, the increased life expectancy of the HIV-infected population. The number of elderly HIV+ individuals is dramatically increasing, and nowadays, approximately one-half of the people living with HIV in the United States are age 50 or older (5). In this sense, aging itself is a condition associated with a chronic inflammation and immune senescence, contributing to accelerate age-related morbidity. Second, the persistent inflammatory state and activation of the immune system also induced by the HIV-infection, per se. This condition amplifies the risk of age-related morbidity (6-9). Finally, antiretroviral-related toxicities contribute to accelerate the apparition of some of these diseases such as the dyslipidemia and cardiovascular events (mainly associated with the protease inhibitors use), renal damage or low bone mineral density (especially by tenofovir and probably also by protease inhibitors).

As a consequence, one of the current aims of HIV management is the management of chronic non-infectious co-morbidities in an increasingly older and more complex population. The use of the newest and more safety antiretroviral drugs is a mandatory strategy, especially in this elderly population, to achieve a maintained viral suppression. However, there are many published studies showing higher levels of inflammation even in patients under a viral suppression, in comparison with general population. Regarding this condition, the investigators currently lack effective interventions to potently block this inflammatory status. Although some initial data are published about this regard, data in elderly HIV-infected people are lacking.

Based on these data, the investigators propose a strategy for treatment of elderly HIV-infected patients with a double impact on systemic inflammation and age-related co-morbidities by switching the protease inhibitors by raltegravir, a integrase inhibitor with a neutral effect on lipid and bone metabolism, and adding an statin because of their anti-inflammatory effect. For safety reasons, only patients with maintained viral suppression (documented indetectable viral load for 1 year or more), and no history of virological failure to integrase inhibitors or suspected or documented resistance mutations to the integrase or retrotranscription will be candidates for the study.