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New antiretroviral drug classes provide opportunities to explore novel regimens.HIV+ adults (<50 copies/mL) receiving atazanavir (ATV) were randomized to raltegravir (RAL) 400 mg + ATV 300 mg twice daily (q12h) for 4 weeks followed by RAL 800 mg + ATV/ritonavir 300/100 mg once daily (q24h) for 4 weeks or vice versa. Validated assays quantitated RAL and ATV plasma concentrations. Primary endpoint was geometric mean ratio (GMR) of ATV minimum concentration (Cmin) for q24h/q12h. Equivalence was 90% confidence interval (CI) of GMR lying between 0.80 and 1.25. Participants could consent to a total 48-week follow-up.Twenty-five men, mean age 45 (range, 35-57) years, were evaluated. ATV and RAL demonstrated considerable pharmacokinetic variability. There was no period or sequence effect for pharmacokinetic parameters (P > 0.1 all measures). Ninety percent CIs of ATV GMR Cmin [1.30 (90% CI: 1.08 to 1.58)] and RAL GMR Cmin [0.48 (90% CI: 0.31 to 0.75)] demonstrated nonequivalence. Seventy-six percent consented to follow-up. There were no serious adverse events and no discontinuations due to adverse events over 48 weeks; HIV RNA remained undetectable.In virologically suppressed adults, regimens comprising ATV plus RAL were efficacious and safe. ATV q12h troughs were lower than ritonavir-boosted atazanavir q24h; RAL q24h troughs were lower than q12h. [ABSTRACT FROM AUTHOR]

Raltegravir is uncommonly associated with rhabdomyolysis and grade 3-4 creatine kinase (CK) elevation. In this cross-sectional study, we compared the prevalence of skeletal muscle toxicity in HIV-infected adults receiving raltegravir with that of a control group.Adults receiving combination antiretroviral therapy were recruited consecutively. Assessments included physical examination, an exercise questionnaire, and blood testing for CK, troponin T, and raltegravir trough levels. The primary endpoint was the prevalence of skeletal muscle toxicity, defined as a composite of any of the following: (1) isolated CK elevation; (2) myalgia; (3) proximal myopathy on examination; or (4) rhabdomyolysis.A total of 318 participants (159 raltegravir, 159 control) were evaluated; 98% were male, 89% white, with median age 51 years, and 91% had HIV-1 RNA <50 copies per milliliter. Mean raltegravir exposure was 28 months. Skeletal muscle toxicity was present in 37% of the raltegravir vs. 19% of the control group (P < 0.001). By component, there were significant respective differences in myalgia (19% vs. 3%, P < 0.001) and proximal myopathy (4% vs. 0%, P = 0.030) but not CK elevation (14% vs. 16%, P = 0.639). No patient had rhabdomyolysis. In multivariate analysis, raltegravir therapy (P < 0.001) and strenuous exercise (P = 0.002) were independently associated with overall muscle toxicity. No component of muscle toxicity was associated with duration of raltegravir or the raltegravir level.Raltegravir-based therapy is associated with a higher prevalence of symptomatic skeletal muscle toxicity, which does not seem to be concentration or time dependent, nor associated with elevated CK. Proximal myopathy may be an uncommon but significant side effect of raltegravir exposure. [ABSTRACT FROM AUTHOR]