Knowledge and attitudes in the prevention of vertical transmission of HIV in referral hospitals.

Background: Prevention of HIV vertical transmission programmes (VTPs) in South Africa has decreased paediatric HIV. These programmes require integration in referral hospitals. Objectives: To determine knowledge of and attitudes to the national VTP guidelines in staff from Obstetric and Paediatric disciplines at two referral hospitals. Method: Using a cross-sectional design, a questionnaire to assess knowledge of the guidelines and attitudes (awareness, ease-of-use and non-silo practice, measuring integrated practice) was developed and validated locally. Using standard statistical analyses, data from these questionnaires were used to draw comparisons and determine factors associated with knowledge and attitudes. Results: Of the 249 participants, 138 (55.4%) were in obstetrics, 125 (50.2%) were nurses, and 168 (67.5%) self-identified as junior staff. Knowledge scores were good, median score (Q1-Q3) was 91.7% (79.1-95.8), and higher in those who had discipline-specific training (P = 0.003). Junior staff (P = 0.002) had higher knowledge levels than senior staff. Most (80%) found the guidelines easy to use and had good awareness, which correlated with knowledge and training. Gaps included understanding of antenatal testing of HIV-negative women and timelines for neonatal HIV testing. Staff scored poorly on integrated practice; the median score (Q1-Q3) was 50% (33.3-58.3), which was inversely correlated with knowledge (r= -0.146, n = 249, P = 0.022). Conclusion: Staff in referral hospitals appear to be practising within silos when implementing VTPs, and this may result in failures to ensure integrated practice. Regularised interdisciplinary and interprofessional training may be important to ensure the integrated implementation of VTPs in referral hospitals.

COVID-19 and HIV viral load suppression in children and adolescents in Durban, South Africa.

Background: The coronavirus disease 2019 (COVID-19) pandemic poses challenges to paediatric and adolescent HIV treatment programme. Modelling exercises raised concerns over potential impact of disruptions. Objectives: To describe the impact of the COVID-19 pandemic on viral load (VL) testing among infants, children and adolescents on antiretroviral treatment (ART) in Durban, South Africa. Method: Routinely collected, aggregated data of monthly VL counts done on all those less than 19 years old from January 2018 to January 2022 was analysed. An interrupted time series analysis using a Prais-Winsten linear regression model, including terms for lockdowns and excess mortality determined VL trends. Results: The unadjusted mean VL was 2166 (confidence interval [CI]: 252.2) and 2016 (CI: 241.9), P = 0.039, and percentage VL suppression rates (72.9%, CI: 2.4% vs 73.6%, CI: 1.8%) across COVID and pre-COVID periods, showing no significant difference, P = 0.262. In the interrupted time series analysis, modelled monthly VL counts did not differ significantly by lockdown level (e.g., level 5 lockdown: -210.5 VLs, 95% CI: -483.0 to +62.1, P = 0.138) or excess mortality (-0.1, 95% CI: -6.3 to 6.1, P = 0.969). A significant downward trend in VL testing over time, including during the pre-COVID-19 period (-6.6 VL per month, 95% CI: -10.4 to -2.7, P = 0.002), was identified. Conclusion: Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19. What this study adds: Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic.

Self-Directed Learning During the COVID-19 Pandemic: Perspectives of South African Final-Year Health Professions Students.

PURPOSE: Self-directed learning (SDL) has been advocated for effective training of final-year health professions students. COVID-19 challenges conventional teaching, learning, and assessment in the clinical environment. This study aimed to identify and explore enablers and barriers to SDL among final-year health professions students training during the COVID-19 pandemic. METHODS: Adopting the SWOT (strengths, weaknesses, opportunities and threats) framework, this study explored the clinical learning and training experiences of final-year health professions students during the pandemic. A survey was conducted via online platforms. Data from 155 respondents were thematically analyzed. RESULTS: Personal attributes such as reflection, self-determination, motivation, resilience, and positive learning behaviors and skills were identified as SDL enablers. Collaborative learning networks and online learning platforms facilitate learning needs and goals. Fear and anxiety, untrusted learning sites, uncertainty about graduation, financial issues and challenges in the learning environments were the major themes related to barriers to SDL. CONCLUSION: The importance of SDL as a skill for uncertain times warrants further investigation in the training of future healthcare professionals. Inclusive planning and engagement with final-year health professions students to address identified stressors, as well as the creation of shared platforms where students are part of the decision-making processes for clinical learning and training are recommended. Responsive curricula that optimize unpredictable disruptions in clinical training are needed to equip students to diagnose their own learning needs and implement appropriate learning strategies.

Pharmacokinetics and safety of early nevirapine-based antiretroviral therapy for neonates at high risk for perinatal HIV infection: a phase 1/2 proof of concept study.

BACKGROUND: With increasing intention to treat HIV as early as possible, evidence to confirm the safety and therapeutic drug concentrations of a nevirapine-based antiretroviral regimen in the early neonatal period is needed. This study aims to establish dosing of nevirapine for very early treatment of HIV-exposed neonates at high risk of HIV acquisition. METHODS: IMPAACT P1115 is a multinational phase 1/2 proof-of-concept study in which presumptive treatment for in-utero HIV infection is initiated within 48 h of birth in HIV-exposed neonates at high risk of HIV acquisition. Participants were neonates who were at least 34 weeks gestational age at birth and enrolled within 48 h of birth, born to women with presumed or confirmed HIV infection who had not received antiretrovirals during this pregnancy. The regimen consisted of two nucleoside reverse transcriptase inhibitors plus nevirapine dosed at 6 mg/kg twice daily for term neonates (≥37 weeks gestational age) or 4 mg/kg twice daily for 1 week and 6 mg/kg twice daily thereafter for preterm neonates (34 to <37 weeks gestational age). Here, we report the secondary outcomes of the study: nevirapine exposures in study weeks 1 and 2 and treatment-associated grade 3 or 4 adverse events at least possibly related to study treatment up to study week 4. A population pharmacokinetic model to assess nevirapine exposure was developed from dried blood spot and plasma nevirapine concentrations at study weeks 1 and 2. Nevirapine exposure was assessed in all patients with available blood samples and safety was assessed in all participants. This trial is registered at ClinicalTrials.gov (NCT02140255). FINDINGS: Between Jan 23, 2015, and Sept 4, 2017, 438 neonates were enrolled and included in analyses; 36 had in-utero HIV infection and 389 (89%) were born at term. Neonates without confirmed in-utero HIV infection received nevirapine for a median of 13 days (IQR 7-14). Measured dried blood spot nevirapine concentrations were higher than the minimum HIV treatment target (3 µg/mL) in 314 (90%, 95% CI 86-93) of 349 neonates at week 1 and 174 (87%, 81-91) of 201 at week 2. In Monte-Carlo simulations, week 1 nevirapine concentrations exceeded 3 µg/mL in 80% of term neonates and 82% of preterm neonates. DAIDS grade 3 or 4 adverse events at least possibly related to antiretrovirals occurred in 30 (7%, 95% CI 5-10) of 438 infants but did not lead to nevirapine cessation in any neonates; neutropenia (25 [6%] neonates) and anaemia (six [1%]) were most common. INTERPRETATION: Nevirapine at the dose studied was confirmed to be safe and provides therapeutic exposure concentrations. These data support nevirapine as a component of presumptive HIV treatment in high-risk neonates. FUNDING: National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

The learning environment of paediatric interns in South Africa.

BACKGROUND: South African (SA) paediatric interns (recently qualified medical graduates) work in a high disease burdened and resource deficient environment for two years, prior to independent practice. Perceptions of this learning environment (LE) influences their approaches to training as well as the outcomes of this period of development. Obstacles to creating a supportive LE and supervisor interaction affects the quality of this training. Measuring perceptions of the LE with validated instruments can help inform improvements in learning during this crucial period of medical education. METHODS: The aims of this study was to determine the psychometric qualities of the Postgraduate Hospital Educational Environment Measure (PHEEM) amongst paediatric interns across four hospital complexes in South Africa and to measure the LE as perceived by both interns and their supervisors. Construct validity was tested using factor analysis and internal consistency was measured with Cronbach's alpha. RESULTS: A total of 209 interns and 60 supervisors (69% intern response rate) responded to the questionnaire. The PHEEM was found to be very reliable with an overall Cronbach's alpha of 0.943 and 0.874 for intern and supervisors respectively. Factor analysis using a 3-factor solution accounted for 42% of the variance with the teaching subscale having the best fit compared with the other sub-scales of the original tool. Most interns perceived the learning environment as being more positive than negative however, their perceptions differed significantly from that of their supervisors. Poor infrastructural support from institutions, excessive workloads and inadequate supervision were factors preventing optimal training of paediatric interns. CONCLUSIONS: The SA version of the PHEEM tool used was found to be a reliable and valid instrument for use in interns amongst high disease burdened contexts. Various obstacles to creating an ideal learning environment for paediatric interns were identified to be in need of urgent review. Key differences in perceptions of an ideal learning environment between interns and their supervisors need to be fully explored as these may result in sub-optimal supervision and mentoring.

Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.

BACKGROUND: Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence. METHODS: We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol. FINDINGS: The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001). INTERPRETATION: Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea. RELEVANCE TO PRACTICE: Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.