Prevalence of malnutrition was high before ART initiation. Even though growth improved on ART, some children remained malnourished even after 2 years of ART, highlighting the need for more active nutritional support.

The MONOD ANRS 12206 trial was designated to assess simplification of a successful lopinavir (LPV)-based antiretroviral treatment in HIV-infected children younger than 3 years of age using efavirenz (EFV; 25 mg/kg of body weight/day) to preserve the class of protease inhibitors for children in that age group. In this substudy, EFV concentrations were measured to check the consistency of an EFV dose of 25 mg/kg and to compare it with the 2016 FDA recommended dose. Fifty-two children underwent blood sampling for pharmacokinetic study at 6 months and 12 months after switching to EFV. We applied a Bayesian approach to derive EFV pharmacokinetic parameters using the nonlinear mixed-effect modeling (NONMEM) program. The proportion of midinterval concentrations 12 h after drug intake (C 12 h ) corresponding to the EFV therapeutic pharmacokinetic thresholds (1 to 4 mg/liter) was assessed according to different dose regimens (25 mg/kg in the MONOD study versus the 2016 FDA recommended dose). With both the 25 mg/kg/day dose and the 2016 FDA recommended EFV dose, simulations showed that the majority of C 12 h values were within the therapeutic range (62.6% versus 62.8%). However, there were more children underexposed with the 2016 FDA recommended dose (11.6% versus 1.2%). Conversely, there were more concentrations above the threshold of toxicity with the 25 mg/kg dose (36.2% versus 25.6%), with C 12 h values of up to 15 mg/liter. Only 1 of 52 children was switched back to LPV because of persistent sleeping disorders, but his C 12 h value was within therapeutic ranges. A high EFV dose of 25 mg/kg per day in children under 3 years old achieved satisfactory therapeutic effective levels. However, the 2016 FDA recommended EFV dose appeared to provide more acceptable safe therapeutic profiles. (This study has been registered at ClinicalTrials.gov under identifier NCT01127204.)

Setting Drug resistance threatens tuberculosis (TB) control, particularly among HIV-infected persons. Objective We surveyed antiretroviral therapy (ART) programs from lower-income countries on prevention and management of drug-resistant TB. Design We used online questionnaires to collect program-level data in 47 ART programs in Southern Africa (14), East Africa (8), West Africa (7), Central Africa (5), Latin America (7) and Asia-Pacific (6 programs) in 2012. Patient-level data were collected on 1,002 adult TB patients seen at 40 of the participating ART programs. Results Phenotypic drug susceptibility testing was available at 36 (77%) ART programs, but only used for 22% of all TB patients. Molecular drug resistance testing was available at 33 (70%) programs and used for 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the whole treatment, 16 (34%) during intensive phase only and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line TB regimens; 18 (38%) reported TB drug shortages. Conclusions Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower income countries. DOT was not always implemented and drug supply was regularly interrupted, which may contribute to the global emergence of drug resistance.

In this context of high prevalence of opportunistic infections, a lower exposure to cotrimoxazole in children than adults was noted. To achieve comparable exposure to adults, a dosing scheme per kg was proposed.

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