A randomized trial of the effect of ritonavir in maintaining quality of life in advanced HIV disease

Background: The aim of treatment for HIV disease is prolonging survival and improvement in health-related quality of life. Ritonavir is a potent, orally bioavailable HIV protease inhibitor with demonstrated impact on surrogate endpoints, AIDS-defining disease, and mortality. Objectives: To evaluate the effect of ritonavir combined with reverse transcriptase inhibitor therapy on patient functioning and well-being. Methods: An international, multicenter randomized placebo-controlled clinical trial of ritonavir was conducted in HIV-infected patients with CD4 cell counts less than or equal to 100 X 10 super(6)/l. A total of 1090 patients were randomized to ritonavir and continued treatment with as many as two nucleoside agents (n = 543) or placebo and continued treatment with as many as two nucleoside agents (n = 547). Health-related quality of life was measured at baseline and after 3 and 6 months of treatment using the Medical Outcomes Study HIV Health Survey (MOS-HIV) and HIV-related symptoms scale. MOS-HIV contains 10 subscales and two summary scores (physical health and mental health). Results: The two treatment groups were comparable on baseline CD4 cell counts, demographic characteristics, and MOS-HIV and HIV symptom subscale scores. After 3 months, statistically significant differences (P < 0.03) favoring the ritonavir-treated patients were seen on the physical health summary, mental health summary, and general health perceptions, social function, mental health, and energy/fatigue subscales. After 6 months of ritonavir therapy, significant differences were observed on physical health and mental health summary scores (P < 0.001), and on measures of general health perceptions, physical function, role function, social function, cognitive function, mental health, health distress, energy/fatigue, and overall ratings of quality of life (P < 0.01). Ritonavir-treated patients reported fewer fever symptoms and neurologic symptoms than the placebo group after 6 months of treatment (P less than or equal to 0.005). Conclusions: Ritonavir therapy, combined with other antiretroviral treatments, significantly contributes to maintenance of functioning and well-being over at least 6 months in patients with advanced HIV disease.