Population pharmacokinetic model of rifampicin for personalized tuberculosis pharmacotherapy: Effects of SLCO1B1 polymorphisms on drug exposure.

BACKGROUND: Rifampicin (RIF) exhibits high pharmacokinetic (PK) variability among individuals; a low plasma concentration might result in unfavorable treatment outcomes and drug resistance. This study evaluated the contributions of non- and genetic factors to the interindividual variability of RIF exposure, then suggested initial doses for patients with different weight bands. METHODS: This multicenter prospective cohort study in Korea analyzed demographic and clinical data, the solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes, and RIF concentrations. Population PK modeling and simulations were conducted using nonlinear mixed-effect modeling. RESULTS: In total, 879 tuberculosis (TB) patients were divided into a training dataset (510 patients) and a test dataset (359 patients). A one-compartment model with allometric scaling for effect of body size best described the RIF PKs. The apparent clearance (CL/F) was 16.6% higher among patients in the SLCO1B1 rs4149056 wild-type group than among patients in variant group, significantly decreasing RIF exposure in the wild-type group. The developed model showed better predictive performance compared with previously reported models. We also suggested that patients with body weights of <40 kg, 40-55 kg, 55-70 kg, and >70 kg patients receive RIF doses of 450, 600, 750, and 1050 mg/day, respectively. CONCLUSIONS: Total body weight and SLCO1B1 rs4149056 genotypes were the most significant covariates that affected RIF CL/F variability in Korean TB patients. We suggest initial doses of RIF based on World Health Organization weight-band classifications. The model may be implemented in treatment monitoring for TB patients.

Lay provider HIV testing: A promising strategy to reach the undiagnosed key populations in Vietnam.

BACKGROUND: In Vietnam, reaching the remaining one-third of undiagnosed people living with HIV and facilitating their antiretroviral therapy (ART) enrollment requires breakthrough approaches. We piloted lay provider HIV testing as an innovative approach to reach at-risk populations that never or infrequently HIV test at facility-based services. METHODS: We conducted a cross-sectional survey and analysis of routine program data in two urban provinces (Hanoi and Ho Chi Minh City) and two rural mountainous provinces (Nghe An and Dien Bien) from October 2015 through September 2017. Acceptability of lay provider testing was defined as the proportion of first-time HIV testers utilizing the service, and effectiveness was measured by HIV positivity and ART initiation rates. Univariate and multivariate analyses were used to determine lay provider testing preference and factors associated with that preference. RESULTS: Among 1,230 individuals recruited for face-to-face interviews, 74% belonged to key populations: people who inject drugs accounted for 31.4%; men who have sex with men, 60.4%; and female sex workers, 8.2%. Most clients (67%) reported being first-time HIV testers, and the majority (85.8%) preferred lay provider testing to facility-based testing. Multivariate analysis found that clients in urban areas (adjusted odds ratio [aOR] = 2.50; 95% confidence interval [CI]: 1.30-4.90) and those who had a university or higher education (aOR = 1.83; 95% CI: 1.05-3.20) were more likely to prefer lay provider testing. Lay provider testing yielded a higher HIV positivity rate (4.1%), particularly among first-time testers (6.8%), compared to facility-based testing (nationally estimated at 1.6% in 2016) and had a high ART initiation rate (91%). CONCLUSIONS: Our findings suggest that lay provider HIV testing is an effective approach to reach previously unreached at-risk populations, and, therefore, a critical addition to accelerating Vietnam's attainment of the Joint United Nations Programme on HIV/AIDS 90-90-90 goals.