Altered drug exposures of first-line TB drugs in a moxifloxacin-containing treatment regimen.

BACKGROUND: Pharmacokinetic variability arising from drug-drug interactions and pharmacogenetics may influence the effectiveness of treatment regimens for TB. The Improving Treatment Success Trial compared the WHO-recommended standard treatment in TB patients with an experimental regimen substituting ethambutol with moxifloxacin (MFX) in Durban, South Africa.METHODS: Non-linear mixed-effects modelling was used to investigate the population pharmacokinetics of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA). A total of 25 single-nucleotide polymorphisms, including pregnane-X-receptor, were selected for analysis.RESULTS: TB drug concentrations were available in a subset of 101 patients: 58 in the MFX arm and 43 in the control arm. Baseline characteristics were well-balanced between study arms: median age and weight were respectively 36 years and 57.7 kg; 75.2% of the patients were living with HIV. Although weight-based drug dosing was the same in the two arms, we found that RIF exposure was increased by 19.3%, INH decreased by 19% and PZA decreased by 19.2% when administered as part of the MFX-containing regimen. Genetic variation in pregnane-X-receptor (rs2472677) was associated with a 25.3% reduction in RIF exposure.CONCLUSION: Optimised weight-based TB treatment dosing is essential when RIF, INH and PZA are co-administered with fluoroquinolones. The reduction in RIF exposure associated with pharmacogenetic variation is worrying.

The price of adherence: qualitative findings from HIV positive individuals purchasing fixed-dose combination generic HIV antiretroviral therapy in Kampala, Uganda.

Contrary to early expectations, recent studies have shown near-perfect adherence to HIV antiretrovirals in sub-Saharan Africa We conducted qualitative interviews with patients purchasing low-cost, generic antiretroviral therapy to better understand the social dynamics underlying these findings. We found that concerns for family well-being motivate adherence, yet, the financial sacrifices necessary to secure therapy may paradoxically undermine family welfare. We suggest that missed doses may be more due to a failure to access medication rather than a failure to adhere to medications, and that structural rather than behavioral interventions may be most useful to insure optimal treatment response.

Luxation of the eyeball.

Luxation of the eyeball in two African patients is reported for its rarity. It followed minor trauma to the face and was reduced in both cases without permanent visual disability.