Abstract
Background Despite advances in antiretroviral therapy (ART), a subset of people living with HIV (PLWH) remain on outdated regimens (OUT-ART), which are associated with higher toxicity, reduced tolerability, and increased pill burden. We conducted a cross-sectional, observational study at a tertiary HIV clinic in Northern Italy to assess the prevalence, clinical characteristics, and switch feasibility of PLWH on OUT-ART. Methods The study enrolled all PLWH currently receiving OUT-ART who had attended at least one clinical visit between January 2023 and January 2024 at the HIV outpatient clinics of the Infectious Diseases Unit, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia in Brescia, Italy. Eligible participants were aged ≥18 years, had sustained virological suppression (HIV-RNA < 50 copies/mL), and were receiving ART regimens not listed as first-line or alternative options in the 2023 EACS guidelines. Participants were categorized into two groups: those for whom a switch to an integrase inhibitor-based single-tablet regimen (INI STR) was feasible (Group A) and those for whom it was not (Group B). Demographic, clinical, resistance, and adverse drug reaction (ADR) data were analyzed using descriptive statistics. To evaluate factors associated with the feasibility of switching to an INI-based STR and its relationship with ADR, we performed multivariate logistic regression with multiple imputation and Firth's correction on normalized data. Results Among 3,848 PLWH in care, 54 (1.4%) were on OUT-ART, and 40 (1.0%) met inclusion criteria: Group A comprised 22 individuals; Group B, 18. Our sample had a mean age of 55.4 (± 9.2) years and a mean duration of HIV infection of 24.1 (± 8.8) years, with a generally preserved immunological profile. Genotypic resistance analysis revealed a high prevalence of thymidine analogue mutations in both groups, with non-significantly higher rates of K65R, M184V. INI-resistance mutations were rare. Mild-to-moderate biochemical ADRs were frequent in both groups (63.6% vs. 72.2%, p=0.564), with Group B showing significantly higher rates of hyperbilirubinemia (27.8% vs. 4.5%, p=0.041) and metabolic alterations (27.8% vs. 0%, p=0.008). Multivariate analysis showed that patient refusal was the only variable significantly associated with continued OUT-ART use despite eligibility for switching (OR=581.8; 95% CI: 2.5-134035.4; p=0.0279). Conclusions Patient preference, rather than clinical or virological factors, was the main barrier to regimen optimization. These findings emphasize the need for shared decision-making strategies to improve care in aging, treatment-experienced HIV populations.