BackgroundThe unparalleled success of combination antiretroviral therapy (cART) is based on the combination of three drugs from two classes. There is insufficient evidence whether simplification to ritonavir boosted protease inhibitor (PI/r) monotherapy in virologically suppressed HIV-infected patients is effective and safe to reduce cART side effects and costs.MethodsWe systematically searched Medline, Embase, the Cochrane Library, conference proceedings and trial registries to identify all randomised controlled trials comparing PI/r monotherapy to cART in suppressed patients. We calculated in an intention to treat (loss-of follow-up, discontinuation of assigned drugs equals failure) and per-protocol analysis (exclusion of protocol violators following randomisation) and based on three different definitions for virological failure pooled risk ratios for remaining virologically suppressed.FindingsWe identified 10 trials comparing 3 different PIs with cART based on a PI/r plus 2 reverse transcriptase inhibitors in 1189 patients. With the most conservative approach (viral load <50 copies/ml on two consecutive measurements), the risk ratios for viral suppression at 48 weeks of PI/r monotherapy compared to cART were in the ITT analysis 0.94 8 (95% CI 0.89 to 1.00) p = 0.06; risk difference −0.06 (95%CI -0.11 to 0) p = 0.05, p for heterogeneity = 0.08, I2 = 43.1%) and in the PP analysis 0.93 ((95%CI 0.90 to 0.97) p<0.001; risk difference −0.07 (95%CI −0.10 to −0.03) p<0.001, p for heterogeneity = 0.44, I2 = 0%). Reintroduction of cART in 44 patients with virological failure led in 93% to de-novo viral suppression.InterpretationVirologically well suppressed HIV-infected patients have a lower chance to maintain viral suppression when switching from cART to PI/r monotherapy. Failing patients achieve high rates of de-novo viral suppression following reintroduction of reverse transcriptase inhibitors.
Among protease inhibitors, atazanavir has not been associated with urolithiasis in clinical studies. We describe 11 cases of atazanavir-associated urolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients with low water intake, high urinary pH, and a prior history of urinary stones may have a higher risk of atazanavir-associated urine crystallization.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.