Compared with a regimen of didanosine, lamivudine, and EFV, a regimen of once-daily didanosine, lamivudine, and NVP was inferior and was associated with more frequent virologic failure and death. Clinical Trials Registration. NCT00332306.

BackgroundShortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.MethodsNewly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens.ResultsOf 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification.Conclusions4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB.Trial RegistrationClinical Trials Registry of India CTRI/2012/10/003060

We compared the nutritional status of individuals with human immunodeficiency virus (HIV) infection alone, individuals with HIV infection and tuberculosis (after completion of antituberculosis treatment), and HIV-negative individuals and found that malnutrition, anemia, and hypoalbuminemia were most pronounced among HIV-positive patients with tuberculosis. Weight loss was associated with loss of fat in female patients and with loss of body cell mass in male patients.

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (C max ) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median C max and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC 0 -8 ]) of INH (C max , 2.5 versus 5.1 g/ml, respectively [P ‫؍‬ 0.016]; AUC 0 -8 , 11.1 versus 22.0 g/ml · h, respectively [P ‫؍‬ 0.047[) and PZA (C max , 34.1 versus 42.3 g/ml, respectively [P ‫؍‬ 0.055]; AUC 0 -8 , 177.9 versus 221.7 g/ml · h, respectively [P ‫؍‬ 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median C max of RMP (1.0 versus 2.8 g/ml, respectively; P ‫؍‬ 0.002) and PZA (31.9 versus 44.4 g/ml, respectively; P ‫؍‬ 0.045) were significantly lower. Among all factors studied, the PZA C max influenced TB treatment outcome (P ‫؍‬ 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP C max . The PZA C max significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.

HIV-infected patients with tuberculosis who initiate nonnucleoside reverse-transcriptase-based anti-retroviral treatment in combination with rifampicin-based antituberculosis treatment demonstrate increases in total cholesterol, low-density cholesterol, and high-density cholesterol levels but no change in blood glucose level after 1 year. Cholesterol increases were more frequent among patients receiving efavirenz.