An Observational Retrospective Database Analysis to Evaluate Raltegravir Based-regimens, Including NUC-sparing Regimens, in Aged HIV Patients (RalAge)

Objectives The primary endpoint will be the description of the proportion of participants with an HIV-1 viral load < 50 copies/mL.

The secondary endpoints will be:

• Change from Baseline in CD4+ T-cell counts, CD8 cell counts, CD4/ CD8 ratio
• Proportion of subjects with laboratory alterations
• Proportion of patients with adverse events (AE), serious adverse events (SAE), also according to their severity

Hypotheses Being this a retrospective study, a formal hypothesis is not formulated. Background and Rationale Antiretroviral therapy has changed the natural history of HIV infection. However, antiretroviral therapy must be maintained for life. Its potential long-term adverse effects may interact synergistically with the ageing process, resulting in a higher incidence of comorbidities. The increasing number of non-antiretroviral drugs used to treat comorbidities may also place the patient at a higher risk of clinically meaningful interactions. Nowadays, efficacy is well demonstrated by all antiretroviral drugs compared with previous times. In fact a substantial number of HIV-infected patients from areas where antiretroviral therapy is widely available have achieved sustained suppression of plasma HIV replication. In contrast, the contributions of antiretroviral therapy to the development and progression of comorbidities and to the risk of potentially severe interactions have gained increasing importance as HIV-infected patients are getting older. More than half of HIV-infected patients aged ≥ 50 years have been reported to suffer from two or more concomitant comorbidities. In some of these patients, maintenance of antiretroviral therapy with combinations including NRTIs or PIs may be challenging. Data on ageing HIV patients under antiretroviral therapy are lacking.

RAL is considered one of the better-tolerated antiretroviral medications, due to limited side effects and few long-term safety concerns. Five-year clinical trial outcomes and clinical experience have demonstrated durable virologic suppression in both treatment-naïve and treatment-experienced patients, including patients with extensive antiretroviral history and documented antiretroviral resistance. Studies have also exhibited low adverse effect rates and reliable long-term safety lending to improved tolerance. Several trials have evaluated the reduction in adverse effects in patients switched from various antiretroviral agents to RAL. Treatment-naïve studies have demonstrated a lipid-neutral effect in patients on RAL-containing regimens. When transitioning patients from a ritonavir-boosted PI regimen, statistically significant decreases in total plasma cholesterol, low-density lipoprotein, and triglycerides were demonstrated. Given its negligible interaction with the cytochrome P450 system, RAL displays minimal drug-drug interactions, making it a good option for ageing patients on multiple medications.