pyrimidinones and Tuberculosis--Pulmonary

South African guidelines recommend protease-inhibitor-based antiretroviral therapy (ART) with lopinavir-ritonavir for human immunodeficiency virus (HIV)-infected children <36 months of age. We investigated factors associated with viral suppression and mortality among young children initiating ART.. Treatment-naive, ART-eligible, HIV-infected children (aged 6-104 weeks) were enrolled in an ART strategies trial in South Africa and initiated protease-inhibitor-based ART. Mortality and the probability of viral suppression (defined as HIV RNA load of <400 copies/mL) by 39 weeks after ART initiation were investigated.. Of 254 children who initiated ART, 99 (39%) were cotreated for tuberculosis during follow-up. The mortality rate was 14%. Factors predicting mortality were lower pre-ART weight-for-age z score and higher HIV RNA load. By 39 weeks, 84% of surviving children achieved viral suppression. Children who were not cotreated for tuberculosis were more likely to achieve viral suppression (94.8%) than were children who were receiving cotreatment at ART initiation (74.2%) or who started tuberculosis cotreatment after ART initiation (51.6%; P < .001). Other factors predicting lower probability of viral suppression were lower pre-ART weight- and length-for-age z score, higher HIV RNA load, and World Health Organization disease stage.. High rates of viral suppression can be achieved among infants and young children who initiate protease-inhibitor-based ART. Cotreatment for tuberculosis reduced viral suppression. How best to treat HIV-infected children who require tuberculosis treatment warrants urgent investigation.

Topics: Antiretroviral Therapy, Highly Active; Antitubercular Agents; Child, Preschool; Drug Therapy, Combination; Ethionamide; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Infant; Isoniazid; Kaplan-Meier Estimate; Lopinavir; Male; Pyrimidinones; Rifampin; Ritonavir; RNA, Viral; South Africa; Tuberculosis, Pulmonary; Viral Load

The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lopinavir in HIV-infected South African children taking standard doses of lopinavir/ritonavir (ratio 4:1).. Lopinavir concentrations were measured in 15 TB/HIV-co-infected paediatric patients who were sampled during and after rifampicin-based TB treatment and in 15 HIV-infected children without TB. During TB therapy, the dose of ritonavir was increased to lopinavir/ritonavir 1:1 in order to compensate for the induction of rifampicin. The children received median (interquartile range=IQR) doses of lopinavir 292 mg/m(2) (274, 309) and ritonavir 301 mg/m(2) (286, 309) twice daily. After TB treatment completion the children received standard doses of lopinavir/ritonavir 4:1 (median [IQR] lopinavir dose 289 mg/m(2) [286, 303] twice daily) as did those without TB (median [IQR] lopinavir dose 265 mg/m(2) [249, 289] twice daily).. Lopinavir oral clearance (CL/F) was about 30% lower in children without TB than in co-infected children treated with super-boosted lopinavir. However, the predicted lopinavir C(min) was above the recommended minimum therapeutic concentration during TB/HIV co-treatment in the 15 children. Lopinavir CL/F increased linearly during the dosing interval.. Increasing the ritonavir dose to achieve a lopinavir/ritonavir ratio of 1:1 when given in combination with rifampicin-based TB treatment did not completely compensate for the enhancement of lopinavir CL/F caused by rifampicin. The time-dependent lopinavir CL/F might be due to a time-dependent recovery from ritonavir inhibition of lopinavir metabolism during the dosing interval.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Infant; Lopinavir; Male; Pyrimidinones; Rifampin; Ritonavir; South Africa; Time Factors; Treatment Outcome; Tuberculosis, Pulmonary

Topics: Adult; Anti-HIV Agents; Antitubercular Agents; Drug Interactions; HIV Infections; Humans; Lopinavir; Male; Panuveitis; Pyrimidinones; Rifabutin; Ritonavir; Tuberculosis, Pulmonary

Parameters of natural and probe fluorescence of peripheral blood lymphocytes have been studied in 25 normal persons and 72 patients suffering from extensive forms of pulmonary tuberculosis who live in various radioecological conditions. It was found that in cell suspension the intensity of fluorescence of protein and the membrane-bound merocyanine 540 dye was 2.0-3.2 and 3.9-7.1 times higher, respectively, for the lymphocytes of the examined patients. For lymphocytes of the patients who live in radionuclide-contaminated areas fluorescence of reduced pyridine nucleotides and some fluorescent probes (ANS, DPGT, the ratio of eximer to monomer fluorescence of pyrene) and the merocyanine-photosensitized cell death were also found to increase. These can indicate some changes of cell membranes and reduction of the oxidation resistance of lymphocytes. There was not any substantial dependence on the changes in the parameters determined in the patients calculated radiation doses was revealed. It was found that biophysical tests, in particular, photosensitized cell death, are informative for estimation of severity of the tuberculous process and prognosis of its outcome in patients who live in adverse radioecological conditions.

Topics: Adult; Anilino Naphthalenesulfonates; Diphenylhexatriene; Fluorescence; Fluorescent Dyes; Humans; Lymphocytes; Male; Middle Aged; Photosensitizing Agents; Power Plants; Pyrimidinones; Radioactive Hazard Release; Republic of Belarus; Tuberculosis, Pulmonary; Ukraine