Effects of switching to protease inhibitor monotherapy on nucleoside analogue-related adverse events.

Switching from triple combination treatment to protease inhibitor monotherapy may increase the risk of elevations in HIV RNA, and is not recommended in most international treatment guidelines. However, the use of protease inhibitor monotherapy could prevent or reverse adverse events related to long-term use of nucleoside analogues, such as lipoatrophy, renal adverse events, osteopenia, and anemia. A detailed MEDLINE search was conducted to identify randomized clinical trials of triple-combination treatment versus protease inhibitor monotherapy with detailed analyses of safety. Summary results from analysis of changes in body composition, changes in lipids, renal adverse events, and anemia were evaluated for patients taking either protease inhibitor monotherapy or triple therapy. In six trials with dual-energy X-ray absorptiometry data available, the percentage of patients with lipoatrophy was significantly lower in the protease inhibitor monotherapy arms than the triple therapy arms (p = 0.03). In these trials there was also no significant difference in the risk of lipohypertrophy between protease inhibitor monotherapy and triple therapy arms. In one trial there was a higher risk of renal adverse events for patients taking tenofovir in the triple therapy arm. In two trials there were rises in total cholesterol when patients stopped taking tenofovir in the protease inhibitor monotherapy arms. In conclusion, there is a mixed pattern of changes in nucleoside analogue-related adverse events after switching from triple therapy to protease inhibitor therapy. The potential for safety benefits of stopping nucleoside analogues needs to be set against a higher risk of HIV RNA elevations during protease inhibitor monotherapy.