abacavir and Tuberculosis--Pulmonary

Optimal treatment of human immunodeficiency virus (HIV)-associated tuberculosis in patients with high CD4⁺ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression.. We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/μL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4⁺ T-cell counts of < 250 cells/μL, AIDS, or death.. Intervention and comparison arms had similar median CD4⁺ counts (517 and 534 cells/μL, respectively) and HIV RNA levels (4.6 and 4.7 log₁₀ copies/μL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis.. Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4⁺T-cell counts of >350 cells/μL was safe and associated with clinical benefits.

Topics: Adolescent; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Dideoxynucleosides; Female; HIV Infections; Humans; Lamivudine; Male; Middle Aged; Survival Analysis; Treatment Outcome; Tuberculosis, Pulmonary; Uganda; Young Adult; Zidovudine

In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.).

Topics: Anti-HIV Agents; Antitubercular Agents; Biological Availability; Child; Child, Preschool; Dideoxynucleosides; Drug Combinations; Drug Interactions; HIV Infections; Humans; Lopinavir; Prospective Studies; Rifampin; Ritonavir; Tuberculosis, Pulmonary

Human immunodeficiency virus (HIV) has caused resurgence in tuberculosis (TB) worldwide. HIV-TB coinfected individuals are at increased risk for complications of TB and HIV treatment, such as adverse drug reactions and immune reconstitution syndrome. A 17-year-old male with HIV-TB coinfection, who developed cardiac tamponade from immune reconstitution during treatment for TB and HIV, is reported in this document.

Topics: Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cardiac Tamponade; Comorbidity; Dideoxynucleosides; HIV Infections; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Pericardial Effusion; Tuberculosis, Pulmonary; Ultrasonography

Triple nucleoside reverse transcriptase inhibitors are recommended as an alternative regimen for HIV-infected patients undergoing tuberculosis treatment in resource-limited settings. Few data exist on the efficacy of such regimens in tuberculosis patients. In 34 tuberculosis/HIV-co-infected patients treated with zidovudine/lamivudine/abacavir, 76% achieved HIV RNA less than 50 copies/ml at 24 weeks. No cases of hypersensitivity or immune reconstitution syndrome were observed. These data support the continuing evaluation of nucleoside-based antiretroviral regimens as an alternative treatment for this population.

Topics: Adult; Antitubercular Agents; CD4 Lymphocyte Count; Dideoxynucleosides; Drug Hypersensitivity; Drug Therapy, Combination; Female; HIV Infections; Humans; Lamivudine; Male; Middle Aged; Neutropenia; Reverse Transcriptase Inhibitors; RNA, Viral; Treatment Outcome; Tuberculosis, Pulmonary; Zidovudine