Valuing Academic Freedom and Advocacy.

This is a correspondence letter in response to an article published in the journal: Flaherman VJ, Nankabirwa V, Ginsburg AS. Promoting Transparent and Equitable Discussion of Controversial Research. Journal of Empirical Research on Human Research Ethics 2023; 18(4): 248-9.

Cohort profile: the Western Cape Pregnancy Exposure Registry (WCPER).

Purpose: The Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures in pregnancy and associations with pregnancy outcomes.

Participants: Established in 2016, all women attending their first antenatal visit at primary care obstetric facilities were enrolled and followed to pregnancy outcome regardless of the site (ie, primary, secondary, tertiary facility). Routine operational obstetric and medical data are digitised from the clinical stationery at the healthcare facilities.

Increased infectious-cause hospitalization among infants who are HIV-exposed uninfected compared with HIV-unexposed.

Objectives: Increased risk of morbidity and hospitalization has been observed in children who are HIV-exposed uninfected (HEU) compared with HIV-unexposed uninfected (HUU). Studies in the era of universal maternal antiretroviral treatment (ART) are limited.

Design: Prospective cohort.

Preterm birth and severe morbidity in hospitalized neonates who are HIV exposed and uninfected compared with HIV unexposed.

Objectives: Infants who are HIV exposed but uninfected (HEU) compared with HIV unexposed uninfected (HUU) have an increased risk of adverse birth outcomes, morbidity and hospitalization. In the era of universal maternal antiretroviral treatment, there are few insights into patterns of neonatal morbidity specifically.

Design: A prospective cohort study.

Translating new evidence into clinical practice: a quasi-experimental controlled before-after study evaluating the effect of a novel outreach mentoring approach on knowledge, attitudes and confidence of health workers providing HIV and infant feeding counselling in South Africa.

Objectives: We report the effectiveness of a mentoring approach to improve health workers' (HWs') knowledge, attitudes and confidence with counselling on HIV and infant feeding.

Design: Quasi-experimental controlled before-after study.

Setting: Randomly selected primary healthcare clinics (n=24 intervention, n=12 comparison); two districts, South Africa.

A longitudinal analysis of the completeness of maternal HIV testing, including repeat testing in Cape Town, South Africa.

Introduction: The virtual elimination of mother-to-child transmission of HIV cannot be achieved without complete maternal HIV testing. The World Health Organization recommends that women in high HIV prevalent settings repeat HIV testing in the third trimester, and at delivery or directly thereafter. The Western Cape Province (South Africa) prevention of mother-to-child transmission (PMTCT) guidelines recommend a repeat maternal HIV test between 32 and 34 weeks gestation and at delivery in addition to testing at the first antenatal visit (ideally <20 weeks gestation).

Infectious morbidity of breastfed, HIV-exposed uninfected infants under conditions of universal antiretroviral therapy in South Africa: a prospective cohort study.

Background: Without breastfeeding and maternal antiretroviral therapy (ART), HIV-exposed uninfected (HEU) infants have greater infectious morbidity than HIV-unexposed (HU) infants. We hypothesised that with the introduction of universal maternal ART, breastfed HEU and HU infants would have similar morbidity.

Methods: We prospectively studied a cohort of HIV-infected pregnant women initiating ART, and a parallel group of HIV-uninfected pregnant women, starting from their first antenatal care visit at the Gugulethu Midwife Obstetrics Unit in Cape Town, South Africa.

Serious adverse drug reactions at two children's hospitals in South Africa.

Background: The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children's hospitals.

Methods: We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital.

An educational intervention to update health workers about HIV and infant feeding.

Clinical guidelines are used to translate research findings into evidence-based clinical practice but are frequently not comprehensively adopted by health workers (HWs). HIV and infant feeding guidelines were revised by the World Health Organization to align feeding advice for HIV-exposed and unexposed infants, and these were adopted in South Africa in 2017. We describe an innovative, team-based, mentoring programme developed to update HWs on these guidelines.

Breastfeeding advice for reality: Women's perspectives on primary care support in South Africa.

Breastfeeding education and support are critical health worker skills. Confusion surrounding infant feeding advice linked to the HIV epidemic has reduced the confidence of health workers to support breastfeeding. High antiretroviral therapy coverage of breastfeeding women living with HIV, and an Infant Feeding policy supportive of breastfeeding, now provides an opportunity to improve breastfeeding practices.

Growth trajectories of breastfed HIV-exposed uninfected and HIV-unexposed children under conditions of universal maternal antiretroviral therapy: a prospective study.

Background: Over 1 million HIV-exposed uninfected (HEU) children are born in sub-Saharan Africa annually. Little data exist on the risk of impaired growth in this population under current policies of universal maternal antiretroviral therapy (ART) with breastfeeding. We aimed to study the growth of breastfed HEU children born to women who initiated ART during pregnancy and compare their growth with that of breastfed HIV-unexposed (HU) children drawn from the same community.

Neonatal and infant diagnostic HIV-PCR uptake and associations during three sequential policy periods in Cape Town, South Africa: a longitudinal analysis.

Introduction: To strengthen the early infant diagnosis (EID) programmes and timeously identify and treat HIV-infected infants, birth HIV-PCR for some/all infants has been recommended in the Western Cape, South Africa since 2014. Operational data on the implementation of such programmes in low- and middle-income countries are limited.

Methods: Utilizing the electronic records platform at primary care facilities, we developed an electronic register which consolidated obstetric and HIV-related data, allowing us to track a cohort of HIV-infected/exposed mother/infant dyads longitudinally from antenatal care through delivery to infant HIV-PCR.

HIV Viremia During Pregnancy and Neurodevelopment of HIV-Exposed Uninfected Children in the Context of Universal Antiretroviral Therapy and Breastfeeding: A Prospective Study.

Background: Elevated HIV viral load (VL) in pregnancy has been linked to increased risk of mortality, immunologic abnormalities, infectious morbidity and restricted growth among HIV-exposed uninfected (HEU) children, but little is known about effects on child development.

Methods: HIV-infected women initiating lifelong antiretroviral therapy (ART; tenofovir + emtricitabine + efavirenz) antenatally were followed from first antenatal visit through delivery and with their breastfed infants postpartum. Cognitive, motor and expressive language development (Bayley Scales of Infant and Toddler Development-Third Edition; delay defined as score <85) were assessed on a subset of HEU infants.

Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa.

Objectives: To assess neurodevelopment of breastfed HIV-exposed uninfected (HEU) and breastfed HIV-unexposed children in the context of universal maternal antiretroviral therapy (ART).

Design: Prospective study with antenatal enrolment and follow-up of breastfeeding HEU and HIV-unexposed mother-infant pairs through 12-18 months postpartum.

Setting: Peri-urban community, Cape Town, South Africa.

Field evaluation of HIV point-of-care testing for early infant diagnosis in Cape Town, South Africa.

Background: Early infant HIV diagnosis (EID) coverage and uptake remains challenging. Point-of-care (POC) testing may improve access and turn-around-times, but, while several POC technologies are in development there are few data on their implementation in the field.

Methods: We conducted an implementation study of the Alere q Detect POC system for EID at two public sector health facilities in Cape Town.

Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis Services in Cape Town, South Africa.

Introduction: Polymerase chain reaction testing at birth ("birth-testing") is suggested by new World Health Organization guidelines for rapid diagnosis of infants infected with HIV in utero. However, there are few data on the implementation of this approach in sub-Saharan Africa, and whether birth testing affects uptake of subsequent routine early infant diagnosis (EID) testing at 6-10 weeks of age is unknown.

Methods: We reviewed 575 consecutive infants undergoing targeted high-risk birth testing in Cape Town, South Africa, and matched those testing HIV negative at birth (n = 551) to HIV-exposed infants who did not receive birth testing (n = 551).

Ending preventable child deaths in South Africa: What role can ward-based outreach teams play?

South Africa (SA) has emerged from the Millennium Development Goal era with a mixture of success and failure. The successful national scale-up of prevention of mother-to-child transmission of HIV services with increasingly efficacious antiretroviral regimens has reduced the mother-to-child transmission rate dramatically; however, over the same period there appears to have been no progress in coverage of high-impact interventions for pneumonia and diarrhoea, which are now leading causes of under-5 mortality. SA embarked on a strategy to re-engineer the primary healthcare system in 2011, which included the creation of ward-based outreach teams consisting of community health workers (CHWs).

Laboratory Evaluation of the Alere q Point-of-Care System for Early Infant HIV Diagnosis.

Introduction: Early infant diagnosis (EID) and prompt linkage to care are critical to minimise the high morbidity and mortality associated with infant HIV infection. Attrition in the "EID cascade" is common; however, point-of-care (POC) EID assays with same-day result could facilitate prompt linkage of HIV-infected infant to treatment. Despite a number of POC EID assays in development, few have been independently evaluated and data on new technologies are urgently needed to inform policy.

Recognising and managing increased HIV transmission risk in newborns.

Prevention of mother-to-child transmission (PMTCT) programmes have improved maternal health outcomes and reduced the incidence of paediatric HIV, resulting in improved child health and survival. Nevertheless, high-risk vertical exposures remain common and are responsible for a high proportion of transmissions. In the absence of antiretrovirals (ARVs), an 8- to 12-hour labour has approximately the same 15% risk of transmission as 18 months of mixed feeding.

Nevirapine concentrations in preterm and low birth weight HIV-exposed infants: implications for dosing recommendations.

World Health Organisation guidelines recommend nevirapine 2 mg/kg/d for HIV-exposed infants <2 kg, but 4-6 mg/kg/d for infants >2 kg. In 116 low birth weight infants, nevirapine 2 mg/kg/d until 14 days, and 4 mg/kg/d thereafter, was safe (1 mild possibly related rash) and achieved target plasma concentrations. Concentrations decreased with treatment duration.