ABSTRACT
PURPOSE: Adverse effects are important determinants of quality of life (QOL) during highly active antiretroviral therapy (HAART). The PLATO study investigated the association between changes in patient-reported outcomes including QOL and substitution with lopinavir/ritonavir in patients experiencing side effects (SEs). METHOD: HIV-1-infected participants (N = 849) with undetectable viral load experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized to immediate (baseline) or deferred (week 4) substitution with lopinavir/ritonavir soft-gel capsules 400/100 mg bid. The primary endpoint was change in the total score from the AIDS Clinical Trials Group (ACTG) Symptoms Distress Module (ASDM), supplemented with two items for nephrolithiasis. Secondary endpoints included Medical Outcomes Study (MOS)-HIV scores and Center for Epidemiologic Studies-Depression (CES-D) scores. RESULTS: Immediate substitution resulted in improved ASDM total score at week 4 compared with deferred substitution (p <.001) and significant improvements in all MOS-HIV domains, while significant improvement was observed in CES-D scores at week 8. Primary SEs resolved at week 8 in 65% of participants in the immediate substitution group. Suppression of HIV-1 was maintained. Treatment was well-tolerated and associated with elevations in cholesterol and triglycerides. CONCLUSION: Substitution with LPV/r improved patient-reported outcomes including QOL in patients experiencing Grade-2 SEs, while maintaining viral suppression.
