Background: Antiretroviral therapy (ART) dramatically improves outcomes for children in Africa; however excellent adherence is required for treatment success. This study describes the utility of different measures of adherence in detecting lapses in infants and young children in Cape Town, South Africa.

The effect of rifampicin-based antitubercular treatment on lopinavir concentrations was attenuated by adding ritonavir to rifampicin. Although the median Cmax and AUC0-12 were lowered by 26% and 31%. respectively, the Cmin was greater than the minimum recommended concentration in most children.

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We present a rapid analytic framework for predicting kilonova light curves following neutron star (NS) mergers, where the main input parameters are binary-based properties measurable by gravitational wave detectors (chirp mass and mass ratio, orbital inclination) and properties dependent on the nuclear equation of state (tidal deformability, maximum NS mass). This enables synthesis of a kilonova sample for any NS source population, or determination of the observing depth needed to detect a live kilonova given gravitational wave source parameters in low latency. We validate this code, implemented in the public mosfit package, by fitting it to GW170817. A Bayes factor analysis overwhelmingly (B > 1010) favours the inclusion of an additional luminosity source in addition to lanthanide-poor dynamical ejecta during the first day. This is well fit by a shock-heated cocoon model, though differences in the ejecta structure, opacity or nuclear heating rate cannot be ruled out as alternatives. The emission thereafter is dominated by a lanthanide-rich viscous wind. We find the mass ratio of the binary is q = 0.92 ± 0.07 (90% credible interval). We place tight constraints on the maximum stable NS mass, MTOV $=2.17^{+0.08}_{-0.11}$ M⊙. For a uniform prior in tidal deformability, the radius of a 1.4 M⊙ NS is R1.4 ∼10.7 km. Re-weighting with a prior based on equations of state that support our credible range in MTOV, we derive a final measurement R1.4 $=11.06^{+1.01}_{-0.98}$ km. Applying our code to the second gravitationally-detected neutron star merger, GW190425, we estimate that an associated kilonova would have been fainter (by ∼0.7 mag at one day post-merger) and declined faster than GW170817, underlining the importance of tuning follow-up strategies individually for each GW-detected NS merger.

Concomitant rifampicin-based antitubercular treatment was not an important determinant of efavirenz concentrations. The substantial proportion of participants with estimated Cmin <1 mg/L could result in the rapid emergence of efavirenz-resistant mutations and treatment failure.

Our findings, together with those of previous studies, indicate that many children dosed according to the current guidelines do not achieve adequate efavirenz exposure. Because low efavirenz concentrations are associated with the rapid emergence of efavirenz-resistant mutations and treatment failure, the current recommended efavirenz doses should be re-evaluated, especially in developing countries, where therapeutic drug monitoring is seldom available.

Objectives An efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis. Design Plasma efavirenz concentrations were compared in 40 children during concomitant treatment for tuberculosis and HIV-1, after stopping rifampicin, and in a control group of children without tuberculosis. Associations with antituberculosis treatment, metabolizer genotype (based on CYP2B6 516G→T, 983T→C, and 15582C→T), weight, and time after dose were evaluated. Results Compared to children with extensive metabolizer genotypes, efavirenz concentrations were increased 1.42-fold (95% confidence interval, CI 0.94–2.15) and 2.85-fold (95% CI 1.80–4.52) in children with intermediate and slow metabolizer genotypes, respectively. Concomitant antituberculosis treatment increased efavirenz concentrations 1.49-fold (95% CI 1.10–2.01) in children with slow metabolizer genotypes, but did not affect efavirenz concentrations in extensive or intermediatemetabolizer genotypes. After adjustment for dose/kg, each kilogram of weight was associated with a 2.8% (95% CI 0.9–4.7) decrease in efavirenz concentrations. Despite higher milligram per kilogram doses, a higher proportion of children in the lowest weight band (10–13.9 kg) had efavirenz concentrations less than 1.0 mg/l than larger children. Conclusion Antituberculosis treatment was not associated with reduced efavirenz concentrations in children, which does not support increased efavirenz doses. Children with slow metabolizer genotype have increased efavirenz concentrations during antituberculosis treatment, likely due to isoniazid inhibiting enzymes involved in accessory metabolic pathways for efavirenz.

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