In HIV-infected patients from a low prevalence TB country, both interferon-gamma assays are more sensitive than TST, but seem to be less sensitive than in immunocompetent patients. The blood tests show poor agreement and differ in their dependence on the CD4 cell count.

Objective The human immundeficiency virus (HIV) protease inhibitor atazanavir is often used in once-daily observed therapy of methadone substituted former opiate drug users. We performed a matched-pairs analysis on 24 patients (12 men/women) taking atazanavir/ritonavir 300/100 mg daily plus reverse transcriptase inhibitors, with (n=12) or without (n=12) methadone co-administration. Methods Twenty-four-hour pharmacokinetic profiles of atazanavir/ritonavir were assessed at steady-state and measured by liquid chromatography-tandem mass spectrometry. The geometric mean (GM, t test) minimum and maximum plasma drug concentrations (C min , C max ), area under the concentration-time curve (AUC), and total clearance (CL total ) were compared between the groups of pairs, which were matched for age, sex, weight, and ethnicity. Results The GM [90% confidence interval (CI)] of the atazanavir C min , C max , and AUC of patients taking the methadone oral solution at doses of 20-175 mg/day simultaneously with antiretroviral therapy were impaired compared to patients not taking methadone oral solution: C min =315 (range 197-448) vs. 519 (279-793) ng/mL [GM ratio (GMR)=0.61, p=0.229]; C max =1714 (1238-2262) vs. 3190 (2412-4076) ng/mL (GMR=0.54, p=0.018); AUC=21,987 (15,870-29,327) vs. 35,572 (26,211-46,728) ng h/mL (GMR=0.62, p=0.074). Methadone dose, which is proportional to the amount of methadone oral solution (10 mg/mL), was significantly correlated to atazanavir C max (r 2 =0.40, p=0.001) and AUC (r 2 =0.32, p=0.006). Ritonavir pharmacokinetics was similar between the groups with C min , C max , and AUC GMR of 1.01, 0.80, and 0.96, respectively. Conclusion The partial decrease in atazanavir plasma concentrations in patients concomitantly taking racemic methadone oral solution in this daily observed therapy setting deserves further attention, and therapeutic drug monitoring should be considered.

The evolution of intra-host human immunodeficiency virus type 1 (HIV-1) quasispecies prior and after treating active tuberculosis (TB) with chemotherapy in HIV-1/TB patients was assessed. Two time points HIV-1 quasispecies were evaluated by comparing HIV-1-infected patients with active tuberculosis (HIV-1/TB) and HIV-1-infected patients without tuberculosis (HIV-1/non-TB). Plasma samples were obtained from the Frankfurt HIV cohort, and HIV-1 RNA was isolated. C2V5 env was amplified by PCR and molecular cloning was performed. Eight to twenty-five clones were sequenced from each patient. Various phylogenetic analyses were performed. We found a significant increase in diversity and divergence in HIV-1/TB compared to the HIV-1/non-TB. For HIV-1/TB, the average rate of evolution of C2V5 env was higher than previous reports (2.4 × 10(-4) substitution/site/day). Two groups of HIV-1/TB were observed based on the rate of HIV-1 evolution and coreceptor usage: A fast evolving R5-tropic dominating group and a relatively slowly evolving X4 group. The results demonstrated that active TB has an impact on HIV-1 viral diversity and divergence over time. The influence of active TB on longitudinal evolution of HIV-1 may be predominant for R5 viruses.