Observational studies – Completed, closed and published

HVTN 910: (2018) A protocol to assess the persistence of HIV vaccine-induced seropositivity in participants who received vaccine in DAIDS-funded preventive HIV vaccine trials

Principal Investigator: Mrs Kubashni Woeber

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

PI: Dr. Marian Loveday

Aim
To document the treatment, pregnancy and outcomes of women treated for DR-TB during their pregnancy. 

Study methods

A descriptive cohort analysis

Status
Data collection ongoing

Collaboration

• Dr. Jennifer Hughes from the Desmond Tutu TB Centre (DTCC)
• Dr. James Seddon from Imperial College London and the Desmond Tutu TB Centre (DTCC)
• Clinicians at King Dinuzulu Hospital, eThekweni, KwaZulu-Natal.

Study outcomes

• Loveday M, Hughes J, Sunkari B, Master I, Hlangu S, Reddy T, Chotoo S, Green N, Seddon JA. Maternal and infant outcomes among pregnant women treated for multidrug/rifampicin-resistant tuberculosis in South Africa. 2020. https://doi.org/10.1093/cid/ciaa189.
• Study findings included in the 2022 DR-TB WHO guidelines on how pregnant women with DR-TB should be managed

Nested study within the DR-TB during pregnancy study:

Title: To explore maternal and infant concentrations of second-line TB drugs in pregnant women and their infants

PI: Dr. Gary Maartens (UCT), Dr. Richard Court and Dr Catriona Waitt (Liverpool University)

PI MRC: Marian Loveday

Aim
To explore maternal and infant concentrations of the second-line TB drugs in these women and their infants.

Study methods

All recruited participants who have not yet delivered will be screened for eligibility into the pharmacokinetic (PK) analysis to enhance the understanding of drug exposure in pregnant women on therapy for DR-TB. Two PK sampling occasions will be scheduled, the first will be prior to delivery preferably in the third trimester, on a date, which is convenient for the mother and the second at 6 weeks post-delivery to compare drug levels in the pregnant and non-pregnant state.

Status
Recruitment has started and is ongoing.

Study outcomes

• Court R, Gausi K, Mkhize B, Wiesner L, Waitt C, McIlleron H, Maartens G, Denti P, Loveday M. Bedaquiline exposure in pregnancy and breastfeeding in women with rifampicin-resistant tuberculosis. British Journal of Clinical Pharmacology http://doi.org/10.1111/bcp.15380
• Zuma, A. Joubert, M. van der Merwe, J. Norman, C. Waitt, R. Court, M. Loveday, S.Castel, L. Wiesner, Validation and application of a quantitative LC-MS/MS assay for the analysis of first-line anti-tuberculosis drugs, rifabutin and their metabolites in human breast milk, Journal of Chromatography B (2022), doi: https://doi.org/10.1016/j.jchromb.2022.123489

Second nested study within the DR-TB during pregnancy study:

PI: Dr Grant Theron (US)

PI MRC: Dr. Marian Loveday

Aim

To explore whether microbiomes of mothers (airways, breastmilk, vagina, gut) and babies (gut) are potentially affected by treatment, and if so, are any microbiome changes associated with infant outcomes and drug exposure?

Study methods

All recruited participants who have not yet delivered will be screened for eligibility into the microbiome study. Vaginal, gut, breastmilk and sputum samples will be collected from the mother in the 3^rd trimester and 6 weeks, 6 months and 12 months after delivery. Microbiome estimates in each specimen type will be correlated with PK data and clinical outcomes (in mothers and babies).

Status

Recruitment has started and is ongoing.

MRC PI: Dr. Marian Loveday

PI: Prof Helen Cox (UCT)

Aim
To document survival and the recurrence of TB after successful drug-susceptible- and rifampicin-resistant TB treatment

Study methods

A mixed methods cohort study design: We will identify a similar number of patients with TB in Umzinyathi and Khayelitsha, matching for age and gender with MDR-TB patients in the same area.  Patients co-infected with HIV and with co-morbid conditions (eg. Diabetes) will be included.

Status
Data collection for Umzinyathi is complete. The qualitative data component has been analysed and submitted for publication. We have been unable to extract quantitative data for Khayelitsha from the PDSA.

Collaboration
Mr Johnny Daniels and Dr. Erika Mohr from Medicins san Frontier (Khayelitsha, South Africa)
Dr. Helen Cox and Dr. Andrew Boulle from UCT

PI: Dr. Marian Loveday

Aims
The aims of the implementation component are:

• To develop and implement a targeted screening approach for diabetes, hypertension, and other diseases and conditions utilizing existing community-based and facility-based health service infrastructure in eThekwini, using an improved diagnostic algorithm aligned with national guidelines. This builds on existing screening efforts against other diseases such as tuberculosis.
• To develop an algorithm alongside our partners that is based on peer-reviewed evidence and in line national guidelines. Subsequently, implement it for treatment, support, and education for these patients and their families. Work with public health and where appropriate private health delivery partners to implement and improve this program in subsequent years in a large, targeted area of the municipality.
• To support the National health services integration initiative by sharing practical operational research in a timely manner, avoiding duplication or parallel, “vertical” disease efforts (HIV, TB, hypertension, diabetes, etc.), improving existing and new health worker capacity in public and private sectors, and implementing a clear sustainability plan at the end of the grant period

The aims of the evaluation component:

1. Document the opportunities and models for improved integration and health service delivery implemented by AA&D and local partners at PHC facilities, schools and in the community.
2. Through the lens of a non-communicable disease (NCD) diabetes and an infectious disease TB document the functioning of the different levels of the health system, the interface and relationship between these layers and the inputs needed to optimize health system functionality across all levels.
3. Document the strategies and interventions required to improve integration and for effective patient-centered services including active case finding, linkage to care, effective education and quality management of both non-communicable and infectious diseases.
4. Monitor the integration of both non-communicable and infectious disease services at a community level, together with the linkages to PHC facility level care. 
5. Using the platform created for the Zero TB Cities Initiative, pilot a program of decentralized, community-based screening and referral for diabetes, hypertension and other conditions (as the basis for using this approach for integrated PHC delivery).
6. Monitor the impact of the introduction of new, complex interventions at a district level and how these impact on and are integrated into existing services. This may include the provision of MDR-TB services, Test and Treat and adolescent HIV prevention.

Study methods

Implementation research

Status
Ongoing

Collaboration
Advance Access & Delivery (AA&D)

eThekweni Metro Health Services

Provincial TB and NCD directorates

Phase 1: The treatment journey of People Living with HIV (PLHIV)

PI: Marian Loveday

Aim

To describe the treatment journeys of PLHIV with sub-optimal retention in care to gain a better understanding of the complexities around HIV disease, its management and the contribution of health system failures to sub-optimal retention in care. (We have defined poor retention in care as a PLHIV who has not taken ART for 30 days in the last two months.)

The specific objectives of the study are:

1. to describe the treatment journey of PLHIV with sub-optimal poor retention in care;
2. to explore the social, structural, economic and cultural factors that influence retention in care;
3. to identify health systems factors which are facilitators or barriers to retention in care. 

Methods

Setting: RK Khan hospital and Don Mackenzie ART clinic for adolescents which are both in eThekwini district in KwaZulu-Natal.

Study design: A mixed methods study design will be used. This will include interviews, participant-generated visual methodologies (PVM) and a review of medical records.

Data collection: Data will be collected using semi-structured interviews in PLHIV ≥ 25 years of age and PVM in those 16 - 24 years old.

Study outcomes

• Loveday M, Furin J, Hlangu S, Mthethwa T, Naidoo T. ‘If I am playing football, I forget that I have this virus’: the challenges and coping strategies of adolescents with perinatally acquired HIV in KwaZulu-Natal, South Africa. BMC Infectious Diseases 2022;22:796.
• Loveday M, Furin J, Hlangu S, Naidoo T. “I am alive because of her”: factors affecting adherence to combination antiretroviral therapy among people living with HIV in KwaZulu-Natal, South Africa. BMC Infectious Diseases 2022;22:680. https://doi.org/10.1186/s12879-022-07667-x

Collaboration

Dr. Jennifer Furin (Department of Global Health and Social Medicine, Harvard Medical School)

Phase 2: The treatment journey of Patients Hospitalised with Advanced HIV Disease (AHD)

Aim

To discern patterns and forces driving hospitalization with AHD.

The objectives of the study are:

1. to describe the treatment journey of PLHIV with sub-optimal poor retention in care people living with HIV who are hospitalised with advanced HIV disease (AHD);
2. to describe the social, structural, economic and cultural factors that influence retention in care resulting in ADH and hospitalisation;
3. to identify health systems factors which are facilitators or barriers to retention in care, AHD and hospitalisation. 
4. To explore the contribution of TB, TB treatment and TB services to AHD and hospitalisation.

Methods

Setting: King Edward VIII Hospital and King Dinuzulu Hospital.

Study design: A mixed methods study design will be used. This will include qualitative interviews and a review of medical records.

Data collection: Data will be collected using semi-structured interviews in PLHIV ≥ 18 who are hospitalised with AHD.

Study outcomes

By describing the treatment journeys of PLHIV with sub-optimal retention in care who are hospitalised with AHD we will get a better understanding of the complexities around HIV disease, its management and the contribution of health system factors.

PI: Nobubelo Ngandu, Ameena Goga

Overview
Several clinical trials are currently underway in search for neutralizing antibody candidates that can effectively prevent HIV infection including prevention of vertical HIV transmission. It is important to understand which neutralizing antibody combinations would be ideal for use in preventing HIV transmission during breastfeeding in the South African context.

Aims
This is study aims to assess the feasibility of using broadly neutralizing antibodies as prophylaxis to protect infants from postnatal HIV infection through breastfeeding, in a South African population dominated by HIV-1 subtype C which has a broad intra-subtype genetic diversity spectrum.

Methods
A facility-based proof-of-concept cross-sectional study is being conducted at Kalafong Provincial Tertiary Hospital. A pilot sample of 12-24 mothers with a current plasma viral load >400 copies/mL will be targeted. Sensitivity to second generation neutralizing antibodies will be assessed in-vitro on viruses isolated from the mother’s breastmilk and compared to viruses isolated from autologous blood plasma. One to three antibodies with good potency and breadth will be identified and used to plan a Phase IIb clinical trial in similar settings.

Collaboration

• South African Breastmilk Reserve
• National Institute for Communicable diseases (NICD)/ National Health Laboratory Services (NHLS)
• University of Pretoria
• Ospedale San Rafaelie
• University of Montpellier

Project status: Phase I (data collection) completed, currently in Phase II

Contact
Dr. Nobubelo Ngandu (Nobubelo.Ngandu@mrc.ac.za), Prof. Ameena Goga (Ameena.Goga@mrc.ac.za

PI: Nobubelo Ngandu, Ameena Goga

Aims
To  measure the prevelance and correlates of: Maternal viral load, Maternal HIV incidence, Infant prophylaxis uptake and Infant feeding practices, in a rural district in Mpumalanga

PHASE 2: To evaluate the effect of COVID-19 pandemic and lockdown on uptake of viral load testing, HIV diagnosis testing, and viral load suppression amongst mothers and infants who participated in this study.

Collaboration

• National department of Health
• Ehlanzeni district PMTCT management
• Right to Care (district partner)
• Academy for Quality Healthcare (AQUAH) (district partner)
• National Institute for Communicable diseases (NICD)/ National Health Laboratory Services (NHLS)
• Wits Health Consortium
• Montpellier University France
• University of Bergen Norway
• Queen Mary University of London UK
• Zvitambo Institute for MCH Research Zimbabwe
• Unviersity of Liverpool UK

Project status:  Manuscript writing

Project outputs: 

• PHANGISA STUDY, Brief Report, 1 March 2022
• Ngandu NK, Lombard CJ, Mbira TE, Puren A, Waitt C, Prendergast AJ, et al. HIV viral load non-suppression and associated factors among pregnant and postpartum women in rural northeastern South Africa: a cross-sectional survey. (https://bmjopen.bmj.com/content/12/3/e058347). 
• Mbira TE. Kufa T, Sherman GG, Ngandu NK on behalf of the PHANGISA study team. Compliance to viral load monitoring schedules among women attending Prevention of Vertical HIV Transmission services before and during the COVID-19 pandemic in Ehlanzeni District, Mpumalanga, South Africa. Springer AIDS & Behaviour. https://link.springer.com/article/10.1007/s10461-023-04192-z

Contact
Dr. Nobubelo Ngandu (Nobubelo.Ngandu@mrc.ac.za),  Prof. Ameena Goga (Ameena.Goga@mrc.ac.za)

PI: Prof. Ameena Goga, Dr Terusha Chetty and Prof. Helen Schneider

Overview

The National Department of Health (NDoH)   implemented an integrated sexual, reproductive, maternal, and newborn health initiative to improve sexual, reproductive, maternal, and neonatal health outcomes in South Africa. The study was implemented in 21 facilities; seven each in the Eastern Cape, Limpopo, and Mpumalanga.  This initiative called “Mphatlalatsane” (meaning “the last star before the dawn”) aimed to reduce unplanned pregnancies, maternal and neonatal mortality, and stillbirths, by testing a potentially replicable quality improvement (QI) model for national scale-up through government adoption and funding. The Mphatlalatsane Initiative introduced QI interventions to make small facility-based changes that the system can absorb and sustain if they work.  The SAMRC, in partnership with the SAMRC Health Services to Systems Research Unit, School of Public Health, University of the Western Cape, evaluated the impact and implementation processes of the Mphatlalatsane Initiative in the QI-intensive sites. The evaluation only focused on the maternal and newborn components.

Collaboration
The NDoH, in collaboration with the South African Medical Research Council, Clinton Health Access Initiative (CHAI), the SAMRC-University of Pretoria Maternal and Infant Health Strategies Unit (SAMRC-UP), the University of Limpopo Trust-Limpopo Initiative for New-born Care, and the University of Western Cape.

Project status
Completed

Project outputs:

• Objective 4a technical report.
• Reader (a resource document on quality improvement literature for maternal, neonatal, and child health), and a Mphatlalatsane newsletter with interviews with Project management staff.
• District and sub-district stewardship of quality and health outcomes: roles, systems and strategies.

Contact person
Dr Terusha Chetty (terusha.chetty@mrc.ac.za)

PI: Prof Prakash Jeena

PI MRC: Prof. Ameena Goga, Dr Terusha Chetty

PI UP: Prof Jeane Cloete, Dr Maria Karsas

PI University of Witswatersrand: Prof David Moore

PI UKZN: Prof Moherndran Archary, Dr Ashendri Pillay

Overview
In South Africa, antimicrobial usage, and the prevalence of paediatric community-acquired infections (CAI) and healthcare-associated infections (HAI) are mostly unknown. More robust evidence is required, given the current context of the COVID-19 pandemic.  A cross-sectional point prevalence survey will be conducted in 2021 over two consecutive months at three tertiary/quaternary health care hospitals in South Africa, namely, Chris Hani Baragwanath Academic Hospital (CHBAH), Inkosi Albert Luthuli Central Hospital (IALCH) and Steve Biko Academic Hospital (SBAH).

Objective

To evaluate the antimicrobial usage and prevalence of neonatal and paediatric CAI and HAI at three regional/tertiary centres in South Africa.

Collaboration
The study is a collaborative effort between the South African Medical Research Council, Steve Biko Academic Hospital, University of Pretoria, and Chris Hani Baragwanath Hospital, University of Witwatersrand.

Project status

Data collection has been completed for this study and data analysis is still underway. Two publications have been released with a further two planned for submission.

The overall prevalence of antimicrobial consumption among children at the three academic hospitals was 22.9% (1,191/5,200; 95% CI 15.5-32.5%). Hospital-specific prevalence rates varied as follows: Hospital A, 29.1% (95% CI 16.3-46.3%); Hospital B, 40.8% (95% CI 22.0-62.6%); and Hospital C, 14.1% (95% CI 8.2-23.0%). Age was a significant predictor of antimicrobial use for HAI, with neonates, older infants (29-364 days), and adolescents (13-15 years) having a 1.64-fold, 1.57-fold, and 2.18-fold higher risk, respectively, versus children aged 6-12 years. Preterm birth, underweight on admission, indwelling devices, surgery since admission, and blood transfusions were significant predictors for HAI.

This study reports on the antimicrobial consumption among children in South African academic hospitals, lower than previous reports from South Africa. Widely varying antimicrobial prescribing practice across institutions was observed. Antimicrobial prescribing patterns differed between CAI and HAI cases, emphasizing the need for tailored interventions and improved infection prevention and control (IPC) measures.

Contact person
Dr. Terusha Chetty (Terusha.Chetty@mrc.ac.za)

PIs: Dr Vundli Ramokolo and Dr Wanga Zembe-Mkabile

Aim

To measure the impact of the COVID-19 pandemic on child morbidity including nutritional status, household food security, and dietary diversity, and access to health services

Methods

Cross-sectional follow-up of participants enrolled in a pregnancy cohort study. Consenting mothers/caregivers will be interviewed on the child’s dietary intake and morbid outcomes, grant access and utilization and other factors. Child anthropometry will be measured and data from the previous cohort study will be used as a baseline.

Project status

Data collection completed and analysis and manuscript writing underway.

Contact person: Dr Vundli Ramokolo (vundli.ramokolo@mrc.ac.za)

Principal investigators: Dr Terusha Chetty and Dr Vundli Ramokolo

Co-investigators: Vuyolwethu Magasana, Duduzile Nsibande, Trisha Ramraj, Ameena Goga, Tarylee Reddy, Nada Abdelatif, Carl Lombard

Aim: To determine the best model for PrEP delivery in pregnant and postpartum women attending health facilities in KwaZulu-Natal.

Methods:

Cross-sectional survey among pregnant or postpartum women attending primary health care and community health centres for antenatal or well-baby care in the iLembe and eThekwini Districts, KwaZulu-Natal, South Africa.  Qualitative individual interviews were also conducted with study pregnant and postpartum women and healthcare providers. Outcomes include PrEP uptake, and provider and participant acceptance of PrEP use.

Contact: Dr Chetty (terusha.chetty@mrc.ac.za), Dr Ramokolo (vundli.ramokolo@mrc.ac.za)

Aim

To assess the nutritional status and dietary patterns of recipients and non-recipients of the CSG in Langa Township, Western Cape

Methods

Community-based prospective pregnancy cohort study conducted in Langa township. Mother-child pairs were recruited during pregnancy and followed until 2 years postpartum. Data on access to the CSG, child feeding practices and anthropometry were collected. 

Status

Data collected between March 2016 and March 2023. Data analysis and manuscript writing underway.

PIs

Dr Wanga Zembe-Mkabile and Dr Vundli Ramokolo

Contact: Dr Wanga Zembe-Mkabile (wanga.zembe@mrc.ac.za), Dr Vundli Ramokolo (vundli.ramokolo@mrc.ac.za)

PIs: Vundli Ramokolo and Parul Puri

Aim: This research project is aimed at generating transferable evidence that supports the screening, identification, and care initiation for maternal multimorbidity in LMIC contexts.

Collaboration: The study is a collaborative effort between the South African Medical Research Council and the George Institute for Global Health.

Status: Study preparations currently underway.

Contact: Dr Vundli Ramokolo (vundli.ramokolo@mrc.ac.za)

PI: Prof. Ameena Goga

Overview
In 2015 South Africa adopted PMTCT Option B+ which recommends lifelong antiretroviral therapy for all pregnant and lactating women regardless of CD4 cell count.

Aim
To document the processes and models used for PMTCT Option B+ implementation, to measure the effects of PMTCT Option B+ on health services for mothers and children and to evaluate early effectiveness of PMTCT Option B+ in the initial 1-2 years post-implementation.

Collaboration
National Department of Health, Centers for Disease Control and Prevention, UNICEF, National Institute for Communicable Diseases

Project status
The project has been completed.  The detailed survey report  is available here.  Research papers for peer reviewed publication are currently being written.

Contact person
Prof. Ameena Goga (ameena.goga@mrc.ac.za)

Publications:

1. Ngandu, N. K., Nsibande, D. F., Magasana, V., Chirinda, W., Mbira, T., Sherman, G. G., & Goga, A. E. (2021). Quality and turnaround times of viral load monitoring under prevention of mother-to-child transmission of HIV Option B+ in six South African districts with a high antenatal HIV burden. South African Medical Journal, 111(8), 759-767.
2. Tshiamo M. Mmotsa, Vuyolwethu Magasana, Duduzile F. Nsibande, Mbongeleni Buthelezi, Reshmi Dassaye, Violeta J. Rodriguez, Deborah L. Jones, Ameena E. Goga and Nobubelo K. Ngandu. Mixed-methods cross-sectional study of the prevention of vertical HIV transmission program users unaware of male partner’s HIV status, in six South African districts with a high antenatal HIV burden. (2023) 23:1988 https://doi.org/10.1186/s12889-023-16921-z.  (Public Health news blog feature: How can more men be encouraged to share their HIV status with pregnant partners? | Be in the KNOW)

PI: Prof. Ameena Goga and Dr. Witness Chirinda

Overview
There are few studies assessing the long-term outcomes, at approximately 3-4 years of age of HIV exposed and HIV unexposed children. These data are critical for monitoring the impact of the national PMTCT programme and the fourth millennium development goal.

Aim
To assess the survival of mothers and their HIV exposed uninfected (HEU) or HIV unexposed infants, previously enrolled in the 2012-14 South African PMTCT Evaluation (SAPMTCTE), at 2-3 years postpartum. Peer-reviewed paper submitted for publication.

Collaboration
UNICEF, National Department of Health

Project status
Data collection completed, analysis and write up in progress.

Contact person
Dr. Witness Chirinda (witness.chirinda@mrc.ac.za)

CoVICIS is a multidisciplinary project involving three countries (South Africa, Italy and Switzerland) to address key questions associated with the evolution of the SARS-CoV-2 pandemic with the ultimate goal of generating scientific data that will contribute to the control of the pandemic through the surveillance of the appearance of variants of concern (VOC) and their spread in the general population (both adult and children) and in targeted populations of interest (vaccinated, post-Covid-19, immunocompromised including those who are infected with HIV). These studies will advance the understanding of the virus biology and evolution through the identification of novel VOC and their virological characterization, as well as the identification of immune correlates of protection of disease and/or vaccination. South Africa contributed children’s data to the COVICIS study through two studies outlined below (COVID KIDS and CoKiDSS) through identification of differences in clinical (asymptomatic versus severe Covid-19) and immune responses in unvaccinated children’s cohorts in South Africa (SA), infected with different VOC.

Protocol chairs: SAMRC: Prof. Ameena Goga and Dr Terusha Chetty

Protocol co-chairs: Dr David Moore; Prof D Moore, Dr Firdose Nakwa, Dr Shannon Cawood, Prof Debbie White, Dr Gary Reubenson, Prof Jeané Cloete, Prof Nicolette du Plessis, Prof Dini Mawela, Prof Ute Feucht, Prof Kate Webb, Prof Chris Scott, Prof Heather Zar: Prof Liesl Zühlke, Dr Kogie Chinniah, Dr Moherndren Archary, Dr Riana van Zyl, Dr Michael Pienaar and Dr Nomakhuwa Tabane.

Overview

The SAMRC HIV And Other Infectious Diseases Unit and Biostatistics Unit was the South African coordinating centre for a study conducted in a network of children’s and maternity hospitals from January 2020 until December 2021 in four countries in Africa and Asia (Ethiopia, India, Pakistan, South Africa). The overall aim is to understand the clinical characteristics of SARS-CoV2 related disease in neonates, children and adolescents aged 0-19 years presenting to hospital in low- and middle-income countries. In South Africa, data was collected from 15 network hospitals across 4 provinces (KZN: Inkosi Albert Luthuli, Mahatma Gandhi Memorial and King Edward VIII; GP: Chris Hani Baragwanath, Nelson Mandela Children’s, Rahima Moosa Mother and Child, Steve Biko Academic, George Mukari Academic, Kalafong; FS: Pelanomi, Universitas, Bongani Regional, Dihlabeng Regional, Boitumelo Regional; WC: Red Cross Children’s). Beyond December 2021, the study is being conducted in a subset of network hospitals with the addition of an immunological sub-study. The immunological sub-study aims to understand immunological responses in 50 children hospitalised with severe COVID-19 and 50 children hospitalised with non-severe COVID-19 as a primary diagnosis or a child with incidental COVID-19.

Collaboration: The study is a collaborative effort between the South African Medical Research Council, University of the Witwatersrand, University of  Pretoria,  Sefako Makgatho Health Sciences University, University of Cape Town, University  of Stellenbosch, University of KwaZulu-Natal,  University of Free State, University of Limpopo, National Institutes of Communicable Diseases, Network for Genomic Surveillance in South Africa (NGS-SA), National Health Laboratory Services (NHLS and the National Department of Health.

Project status

Data collection in progress

Contact person/s: Prof. Ameena Goga (ameena.goga@mrc.ac.za) and/or Dr. Terusha Chetty (Terusha.Chetty@mrc.ac.za)

Co-Principal Investigators (Co-PIs): Dr Reshmi Dassaye and Prof Ameena Goga

Overview:

In low-middle income countries (LMIC), such as South Africa, there is lack of data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections amongst children attending school, including seroprevalence and transmission dynamics. The SAMRC HIV and other Infectious Diseases Unit (HIDRU) is presently implementing a pilot study entitled the COVID kids school study (CoKiDSS) among selected primary schools in Ndwedwe, KwaZulu-Natal. This study will provide data from a LMIC setting on the impact of SARS-CoV-2 on school-attending learners (in grades 1-7), their parents and teachers 3 years after the SARS-CoV-2 pandemic was declared and 16-20 months after resumption of normal school attendance. This study is co-funded through the South African Medical Research Council (Grant # SAMRC-RFA-GIPD-03-2021) and the European Health and Digital Executive Agency (HADEA) (Grant # 101046041).

Objectives:

Primary Objective i) To assess the prevalence of self-reported confirmed SARS-CoV-2 prior infections, prior and current COVID-19 symptoms and seroprevalence of SARS-CoV-2 antibodies in the overall  triad of learners (grades 1-7), their parents/guardians and teachers.

Secondary Objective ii) To determine the prevalence of long COVID-19 symptoms, general health and mental health in participants overall and by SARS-CoV-2 antibody status.

iii) To determine the longitudinal changes in SARS-CoV-2 seroprevalence and symptoms in a sub-set of participants who are followed up.

Exploratory Objectives

iv) To conduct viral genome sequencing and describe transmission dynamics in a sub-group of 30 consenting SARS-CoV-2 positive individuals from the learner-parent-teacher triad and up to 10 of their close contacts.

v) To determine the proportion of asymptomatic contacts who test SARS-CoV-2 positive from objective iv and

 vi) To investigate B- and T-cell responses in the sub-group of SARS-CoV-2 positive individuals enrolled under Objective v and correlate these with symptoms.

Collaboration:

This study is a collaborative effort between the SAMRC, National Department of Health, National Department of Education, National Institute of Communicable Diseases, Institute of Infectious Diseases and Molecular Medicine University of Cape Town, Centre for Epidemic Response and Innovation (CERI) Stellenbosch University and the National Health and Laboratory Services.

Project status: As of 31 October 2023, the cross-sectional and follow-up surveys have been completed and we are currently enrolling participants into the nested case cohort sub-study.

Contact person: Reshmi.Dassaye@mrc.ac.za

Coordinating chairs: SAMRC: Prof Ameena Goga

INSERM/Univ Montpellier/EFS/Univ Antilles, France : Prof Philippe Van de Perre

National Co-PIs: Drs Terusha Chetty and Nobubelo Ngandu

Overview:

Passive immunoprophylaxis by means of human monoclonal antibodies with broadly neutralizing (bNAb) properties is an appealing new strategy to eliminate residual transmission of HIV by breastfeeding (Van de Perre & Goga; Lancet 2021). VRC07-523LS is one such bNAb that has similar but broader applicability than previous products (VRC01 and VRC07). VRC07-523LS targets the CD4 binding site of >96% of viruses including clade C. After a single subcutaneous injection, it is estimated that protection lasts for 3 months in adults and infants. This study aims to characterize the safety and pharmacokinetics of the long-acting broadly neutralizing HIV antibody (bNAb) VRC07-523LS among breastfed HIV-exposed uninfected infants and breastfed HIV-infected infants receiving standard of care antiretroviral treatments (ART) for prophylaxis or treatment. The SAMBULELO Trial is complementary to another trial conducted by the same investigators, the Phase 1/2 PedMAb study. These two trials are meant to prepare for a phase 3 tolerance and efficacy trial of a perinatal VRC07-523LS administration, in a high HIV-1 prevalence and incidence area in South Africa. Should the results be favourable, a phase 3 trial (with support requested among others to SAMRC, ANRS and EDCTP) will be conducted in high HIV prevalence and incidence areas such as in the Ehlanzeni district, close to the Mozambican and Swaziland borders (with 36% of pregnant women being HIV-infected) or in the eThekwini or similar districts. Using bNAbs in PMTCT will be a game changer for paediatric HIV elimination in high HIV prevalence, low-middle income breastfeeding settings as we would not need to rely solely on maternal / infants ART interventions and adherence.

Sites:

• University of Pretoria Clinical Research Site: Steve Biko Academic Hospital (SBAH)
• University of Witwatersrand VIDA Nkanyezi Research Unit: Rahima Moosa Mother and Child Hospital (RMMCH) site

Collaboration:

This study is a collaborative effort between the SAMRC, INSERM/University Montpellier, the University of Pretoria, University of Witwatersrand, the National Institute of Communicable Diseases, National Health Laboratory Services, National Department of Health, ANRS France, Ospedale San Raffaele srl Italia and the University of Bergen.

Project status: The study will be initiated in June 2024.

Contact persons: Terusha.Chetty@mrc.ac.za and/or Nobubelo.Ngandu@mrc.ac.za

Principal Investigators: Ms Vuyolwethu Magasana and Prof Ameena Goga

Overview: There are numerous concerns regarding the current trajectory towards eliminating vertical HIV transmission (EMTCT), signalling the need for a paradigm shift in global efforts to prevent HIV transmission. Furthermore, progress in scaling up access to treatment for children living with HIV has been slow despite evidence that early initiation of ART initiation in infants saves lives. Recent systematic reviews and policy briefs have underscored the need for complementary biomedical strategies to eliminate vertical HIV transmissions. Understanding health care providers, mothers’ and communities’ perspectives and preferences during the product design and development phase, can help align the products to meet their needs and potentially increase the ownership, adoption, uptake, and utilization of such novel products.

Study Aim: The aim of the study will be to collect data on acceptability, usability, and feasibility of bnAbs for prevention of vertical HIV transmission from mothers in high-risk settings (HIV negative and those with HIV) who would be potential end-users and from other key stakeholders, including family members, health care providers and policymakers.

Objectives:  

• To understand acceptability and preferences for product attributes and identify factors that influence the adoption of bnAb prevention products for post-natal prophylaxis among healthcare providers, mothers, family members, and community stakeholders. 
• To dentify special considerations for administering bnAbs to infants in the post-natal period, including challenges, perceived benefits, and feasibility considerations.
• To understand key health system and programmatic perspectives including challenges and feasibility of introducing bnAb for post-natal prophylaxis among health service providers and policy makers

Collaborations: IAVI, UVRI-AIVI HIV Vaccine Program - Uganda, FAMCRU

Project Status: Protocol submitted for ethics approval. Data collection planned to start in March/April 2024.

Contact person: Vuyolwethu Magasana (vuyolwethu.magasana@mrc.ac.za) and Prof Ameena Goga (ameena.goga@mrc.ac.za)

Principal Investigator: Vuyolwethu Magasana

Co-PIs: Ms Duduzile Nsibande, Dr Vundli Ramokolo, Dr Terusha Chetty, Dr Niresh Bhagwandin

Overview: According to UNAIDS data, approximately one-third of PLWHIV who started ART do not have viral suppression. Since universal test and treat advocates for more PLWHIV on ART for longer periods of time, consequently, there is an emergence of HIV drug resistance (HIVDR) which undermines ART efficacy and ultimately jeopardize the 95-95-95 targets. Poor access to care and disengagement from care may result to both high VL and HIVDR and these may ultimately impact on increased new infections. The purpose of this study is to identify strategies to improve the acceptance of positive HIV results, improve treatment access, and establish preferred models of care.

Study Aim: To investigate socio-behavioral factors contributing to non-disclosure of HIV positive status and to understand reasons why people with known HIV positive status get retested at public healthcare centres (PHCs).

Objectives:

• To understand factors facilitating HIV re-testing among PLHIV in PHCs.
• To explore facilitators and barriers of HIV status disclosure among re-testing PLHIV.
• To understand client-centred needs of re-testing for re-engagement, treatment adherence and continuity in care in order to inform case management strategies.
• To explore whether HIV disclosure, or lack thereof, influences retesting behavior and its potential implications on healthcare engagement.

Collaborations: CDC, NICD

Project Status: Completing protocol writing phase. Data collection planned to start in April 2024.

Contact person: Vuyolwethu Magasana (vuyolwethu.magasana@mrc.ac.za) and Niresh Bhagwandin (niresh.bhagwandin@mrc.ac.za)

PI: Dr Nobubelo Ngandu

Aim: This is a district-level pilot study aimed at developing and piloting a centralized digital platform to routinely identify and monitor risk factors for vertical HIV transmission real-time.

BALMM stands for ‘Bona Abantwana, Luleka uMama noMbongi’, meaning ‘See the children, advise the caregivers (including mothers and healthcare workers)’

Funder: Gilead Research Scholars Grant 2023-2024

Collaboration

• KZN provincial department of Health
• University of Witwatersrand

Project status:  The pilot activity was completed in October 2024 and the report can be found here

Contact
Dr. Nobubelo Ngandu (Nobubelo.Ngandu@mrc.ac.za)