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In high prevalence settings, tuberculosis and HIV dual infection and co-treatment is frequent. Rifamycins, especially rifampicin, in combination with isoniazid, ethambutol and pyrazinamide are key components of short-course antituberculosis therapy. Areas covered: We reviewed available data, for which articles were identified by a Pubmed search, on rifamycin-antiretroviral interactions in HIV-infected children. Rifamycins have potent inducing effects on phase I and II drug metabolising enzymes and transporters. Antiretroviral medications are often metabolised by the enzymes induced by rifamycins or may suppress specific enzyme activity leading to drug-drug interactions with rifamycins. These may cause significant alterations in their phamacokinetic and pharmacodynamic properties, and sometimes that of the rifamycin. Recommended strategies to adapt to these interactions include avoidance and dose adjustment. Expert opinion: Despite the importance and frequency of tuberculosis as an opportunistic disease in HIV-infected children, current data on the management of co-treated children is based on few studies. We need new strategies to rapidly assess the use of rifamycins, new anti-tuberculosis drugs and antiretroviral drugs together as information on safety and dosing of individual drugs becomes available.

A growing number of children globally are being treated for multidrug-resistant tuberculosis (MDR-TB). The second-line injectable antituberculosis medications amikacin, kanamycin and capreomycin, traditionally a mainstay of MDR-TB treatment, cause important adverse effects including permanent sensorineural hearing loss, nephrotoxicity, electrolyte abnormalities, injection pain and local injection site complications. Areas covered: To characterize the safety and tolerability of the second-line injectables in children treated for MDR-TB, we reviewed data on the mechanism of injectable associated adverse effects, risk factors for their development, and the incidence of injectable-associated adverse effects in adults and children treated for MDR-TB. Expert opinion: Despite a substantial evidence base in adults demonstrating the frequent and potentially serious adverse effects of second-line injectables, important knowledge gaps remain. Improved characterization of the incidence of injectable-associated adverse effects will inform rational guidance on monitoring children with TB on injectables. Eliminating the need for injectables in MDR-TB treatment regimens is a high priority, and will rely on the use of novel antituberculosis TB drugs. Strategies to reduce the risk of adverse effects of injectables, if used, deserve evaluation. This includes evaluation of potentially otoprotective medications N-acetylcysteine or aspirin, high frequency hearing screening for earlier detection of ototoxicity and therapeutic drug monitoring.

The association of childhood tuberculosis (TB) and malnutrition is known, but treatment response, the influence of the acute-phase response (APR) and concomitant HIV infection are not well documented.To evaluate the nutritional response and APR in HIV-infected and uninfected children hospitalised for the treatment of TB and receiving standard anti-tuberculosis chemotherapy.During a study of the pharmacokinetics of standard anti-tuberculosis agents, anthropometric parameters were measured and blood concentrations of nutrients and C-reactive protein (CRP) determined at 1 and 4 months after initiation of chemotherapy.24 HIV-infected and 34 HIV-uninfected children were studied. On enrollment, 31.6% of HIV-infected and 2.9% of HIV-uninfected children were underweight, and 31.6% and 14.7%, respectively, were stunted. Mean values of weight, height/length, head circumference and mid-upper-arm circumference on enrollment and at 4-month assessment in HIV-infected and uninfected children did not differ. Mean triceps skinfold (TSF) (8.17 and 9.73 cm) and subscapular skinfold (SSF) thicknesses (5.75 and 7.5 cm) on enrollment differed significantly (P = 0.03 and P = 0.003); by 4 months, TSF had declined to 5.97 cm (P0.001) and 8.87 cm (P = 0.05), respectively, and SSF to 5.57 cm (P = 0.79) and 6.73 cm (P = 0.04); the arm muscle area (AMA) was low in a majority of children on enrollment and remained so at the second assessment. CRP was raised in 66.6% and 53.3% of HIV-infected and -uninfected children on enrollment, but at 4-month assessment was raised in 63.2% and 15.2%, respectively. Other micronutrient and haematological findings probably reflect an APR, but no children had sub-normal zinc or magnesium values; most selenium and vitamin C and E values were normal. An elevated platelet count (420 × 10(9)/L) was significantly more common in HIV-uninfected children, and was still raised in 39% at 4 months.A majority of HIV-infected and uninfected children had an APR but it had resolved by 4 months in most HIV-uninfected children. In both groups, low and declining skinfolds and a persistently low AMA indicate a persistent disturbance of fat and protein metabolism, despite successful chemotherapy.

Drug-resistant tuberculosis is a threat to tuberculosis control programs and community health. This growing problem mirrors the increasing incidence of tuberculosis in general. Public health problems include the absence of early diagnosis and effective treatment. The real need is to identify tuberculosis patients far earlier, particularly those with drug-resistant strains, and to begin appropriate therapy, which is of the shortest possible duration with minimal risk of acquiring further drug resistance or permitting further transmission. This article will address the epidemic of drug resistance and discuss some of the inherent difficulties in the treatment of drug-resistant tuberculosis. We highlight some of the controversies and new findings in this area, as well as future perspectives requiring more active interventions, in addition to new technology and developments.