TREATMENT OF human immunodeficiency virus type 1 (HIV-1) infection has evolved dramatically during the past 3 years. Combination therapy with protease inhibitors (PIs) leads to profound and sustained suppression of HIV-1 replication,
1,2 which in turn has resulted in declining HIV-related morbidity and mortality rates in patients with advanced HIV infection.
3 However, exposure to these agents recently has been associated with the development of significant metabolic adverse effects such as hyperlipidemia, peripheral fat wasting, central adiposity, hyperglycemia, insulin resistance, and new-onset diabetes.
4 This spectrum of changes is now thought to be part of a new syndrome associated predominantly with PI use.
5-8 A recent cohort study, which followed up patients already treated with PIs for 21 months, revealed that hyperlipidemia and impaired glucose tolerance were common in PI-treated patients.
6 Nonetheless, there has been no systematic evaluation of PI-treated, HIV-infected patients before and after initiation of PI therapy. Previous studies have not performed mutual adjustment for potential cofounders, including other medication use such as nucleoside reverse-transcriptase inhibitor (NRTI) therapy, body weight changes, or improvement of the underlying HIV status. In addition, it is still unclear whether the components of the metabolic syndrome (glycemia, hypercholesterolemia, hypertriglyceridemia, and body habitus changes) represent an idiosyncratic reaction to PIs manifesting immediately after initiation of therapy or a long-term, progressive pharmacological consequence that evolves over time.