Early initiation of antiretroviral therapy for people newly diagnosed with HIV infection in Australia: trends and predictors, 2004-2015.

OBJECTIVES: To determine trends in and predictors of early treatment for people newly diagnosed with human immunodeficiency virus (HIV) infection in Australia. DESIGN, SETTING: Retrospective cohort analysis of routinely collected longitudinal data from 44 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) program. PARTICIPANTS: Patients diagnosed with HIV infections, January 2004 - June 2015. MAIN OUTCOME MEASURES: Commencement of antiretroviral therapy within 6 months of HIV diagnosis (early treatment); demographic, clinical, and risk group characteristics of patients associated with early treatment; trends in early treatment, by CD4+ cell count at diagnosis. RESULTS: 917 people were diagnosed with HIV infections, their median age was 34 years (interquartile range [IQR]: 27-43 years), and 841 (92%) were men; the median CD4+ cell count at diagnosis was 510 cells/µL (IQR, 350-674 cells/µL). The proportion of patients who received early treatment increased from 17% (15 patients) in 2004-06 to 20% (34 patients) in 2007-09, 34% (95 patients) in 2010-12, and 53% (197 patients) in 2013-15 (trend, P < 0.001). The probability of early treatment, which increased with time, was higher for patients with lower CD4+ cell counts and higher viral loads at diagnosis. CONCLUSIONS: The proportion of people newly diagnosed with HIV in sexual health clinics in Australia who received treatment within 6 months of diagnosis increased from 17% to 53% during 2004-2015, reflecting changes in the CD4+ cell count threshold in treatment guidelines. Nevertheless, further strategies are needed to maximise the benefits of treatment to prevent viral transmission and morbidity.

Lack of enzyme-inducing effect of rifampicin on the pharmacokinetics of enfuvirtide.

The primary objective was to determine whether rifampicin influences the pharmacokinetics of enfuvirtide in HIV-1-infected patients. In a single-center, open-label, one-sequence crossover, clinical pharmacology study, 12 HIV-1-infected adults received enfuvirtide (90 mg, twice daily) on days 1 to 3 and days 11 to 13 (morning dose only on days 3 and 13) and rifampicin (600 mg, once daily) from days 4 to 13. Plasma concentrations were measured for enfuvirtide and its metabolite (days 3 and 13) and rifampicin (day 13 only). The ratios of least squares means (LSM) and 90% confidence intervals for enfuvirtide and enfuvirtide metabolite pharmacokinetic parameters (AUC12h, Cmax, Ctrough) were estimated in the presence and absence of rifampicin. Treatments were compared using an analysis of variance for natural log-transformed variables, with factors patient and treatment. Efficacy and safety were also monitored. Steady-state rifampicin had no appreciable effect on any of the pharmacokinetic parameters assessed for either enfuvirtide or its metabolite. The ratio of LSM for AUC12h, Cmax, and Ctrough for enfuvirtide was 97.5%, 103%, and 84.9%, respectively, and 108%, 112%, and 92.9%, for the enfuvirtide metabolite. Rifampicin did not affect the t1/2 of enfuvirtide or its metabolite. There were no unexpected effects of rifampicin on the short-term antiviral effect or safety of the administered antiretroviral treatment. The pharmacokinetics of enfuvirtide are not induced by a 10-day pretreatment with rifampicin.