Hepatitis B vaccination coverage amongst healthcare workers in a tertiary academic hospital in Gauteng province, South Africa.

Background: Chronic infection with hepatitis B virus (HBV) is a major public health concern in South Africa. Hepatitis B virus is a highly infectious blood-borne virus causing liver disease. Healthcare workers (HCWs) are at high risk of occupational exposure. Objectives: This study aimed to investigate HBV vaccination amongst HCWs at a tertiary academic hospital in Gauteng province, South Africa. Method: Self-administered questionnaires were used to collect data from 500 consecutively sampled HCWs. Data were analysed using Stata version 12. Results: A total of 460 HCWs participated in the study. Most were women (68.7%), < 40 years of age (66.9%) and worked for < 10 years (66.0%). Almost 50.0% were either doctors or medical students and 40.3% were nurses or student nurses. Most HCWs in the age group of < 30 years (79.4%) had received at least 1 dose of HB vaccine. Prevaccination immunity screening was conducted on 17.5% of the HCWs, and only 11.0% reported to be protected against HBV. About 49.0% of HCWs were fully vaccinated. Post-vaccination immunity testing was conducted on 15.1%, and 24.0% of HCWs paid for vaccinations. Nursing staff and those with > 10 years of work experience were 2.5 and 2.6 times more likely to be vaccinated, respectively. Cleaning staff were less likely to be vaccinated. Conclusion: Although not all HCWs were fully vaccinated, our study found a higher proportion of fully vaccinated HCWs than previously reported in Gauteng Province. It is recommended that HB vaccination be promoted and a local vaccination policy, aligned with the national policy, be developed and implemented for all HCWs at the tertiary academic hospital.

Pharmacokinetics, safety and efficacy of maraviroc in treatment-experienced pediatric patients Infected with CCR5-tropic HIV-1

BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults

Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced Pediatric Patients Infected With CCR5-Tropic HIV-1.

BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults.

Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia.

OBJECTIVE: To evaluate the safety of combination antiretroviral therapy (ART) in conception and pregnancy in different health systems. DESIGN: A pilot ART registry to measure the prevalence of birth defects and adverse pregnancy outcomes in South Africa and Zambia. METHODS: HIV-infected pregnant women on ART prior to conception were enrolled until delivery, and their infants were followed until 1 year old. RESULTS: Between October 2010 and April 2011, 600 women were enrolled. The median CD4 cell count at study enrollment was lower in South Africa than Zambia (320 vs. 430 cells/µl; P < 0.01). The most common antiretroviral drugs at the time of conception included stavudine, lamivudine, and nevirapine. There were 16 abortions (2.7%), one ectopic pregnancy (0.2%), 12 (2.0%) stillbirths, and 571 (95.2%) live infants. Deliveries were more often preterm (29.7 vs. 18.4%; P = 0.01) and the infants had lower birth weights (2900 vs. 2995 g; P = 0.11) in Zambia compared to South Africa. Thirty-six infants had birth defects: 13 major and 23 minor. There were more major anomalies detected in South Africa and more minor ones in Zambia. No neonatal deaths were attributed to congenital birth defects. CONCLUSIONS: An Africa-specific, multi-site antiretroviral drug safety registry for pregnant women is feasible. Different prevalence for preterm delivery, delivery mode, and birth defect types between women on preconception ART in South Africa and Zambia highlight the potential impact of health systems on pregnancy outcomes. As countries establish ART drug safety registries, documenting health facility limitations may be as essential as the specific ART details.