Safety and immunovirologic outcomes with maraviroc combination regimens in patients with a history of past treatment failures and virologic resistance in Brazil: an open-label, multicenter phase 3b study.

Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. Of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. The most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). The proportion of patients with viral load <400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining >40% until week 48. At the end of treatment, 26.7% of patients had a viral load <400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/µl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial.

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8) were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study--EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1 percent) completed the study. At the end of treatment, 95.2 percent (CI95: 88.9 percent - 100 percent) reported cure or clinical improvement; at the end of the study, that figure was 88.9 percent (CI95: 74.1 percent - 91.7 percent). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40 percent), and 8 reported presumed eradication (53.3 percent). At end of study evaluation, 9 patients showed pathogen eradication (50 percent), and 7 showed presumed eradication (38.89 percent). Therefore, negative cultures were obtained from 93.3 percent of the patients at EOT, and from 88.9 percent at the end of the study. One patient (6.67 percent of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11 percent) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3 percent of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin...

Mother-to-Infant transmission of hepatitis C virus (HCV) in Brazil.

Sixty-one women with anti-HCV antibodies, detected by a third-generation enzyme immunoassay (EIA3), were prospectively recruited for investigation of vertical HCV transmission during child-birth, at the University Hospital of the Catholic University of Campinas, Brazil, between January 1994 and July 1998. Six of the women presented coinfection with the human immunodeficiency virus type 1 (HIV-1). All of the 72 children born in this period were followed at least until they were 18 months of age. Analyses of anti-HCV, HCV RNA, and alanine aminotransferase were performed in a minimum of two blood samples during follow-up. One (2.4 per cent; 95 per cent CI, 2.2-7) of the 42 children born to HCV viremic mothers was both anti-HCV and HCV RNA-positive, with altered ALT levels. Passively transferred maternal anti-HCV antibodies became undetectable within 9-12 months. None of the nine infants born to HIV-1 infected mothers were infected either by HIV or HCV. Thus, the mother-infant HCV transmission rate is low and seems to be associated with maternal HCV RNA positivity.