Background: GEPPO is a prospective observational multi-centric cohort including HIV-infected geriatric patients. We hypothesized that the GEPPO cohort may help characterize antiretroviral (ARV) prescribing criteria used in real life by Italian infectious disease (ID) physicians. Methods: This was a cross-sectional study describing the current ARV regimen in a geriatric HIV population (≥65 years). Antiretroviral strategies were categorized as follows: (i) multidrug regimens (MDRs), which comprised triple or mega ART combinations; (ii) less drug regimens (LDRs), which comprised fewer than three ART compounds. Multi-morbidity (MM) was defined as the presence of three or more non-communicable diseases, and polypharmacy (PP) as the use of five or more medications in chronic use. Four alternative combinations (MM+PP+, MM+PP-, MM-PP+, MM-PP-) were used in logistic regression analyses. Results: A total of 1222 HIV-positive patients were included (median age 70 years). Females composed 16% of the cohort. Median duration of HIV infection was 17 years; 335 population members had been infected for .20 years. MM was present in 64% and PP in 37% of the patients. Treatment consisted of triple therapy in 66.4%, dual therapy in 25.3%, monotherapy in 6.5% and 'mega-ART' with more than three drugs in 1.64% of the patients. In multivariate logistic regression MM and PP were predictive for mono-dual, NRTI-sparing and tenofovir disoproxil fumarate (TDF)-sparing combinations. Female gender and age were predictors of unboosted ARV regimens. Conclusions: High prevalence of non-conventional ARV regimens in elderly HIV patients suggests that clinicians try to tailor ARV regimens according to age, HIV duration,MMand PP.