The University of Zimbabwe College of Health Science (UZ-CHS) BIRTH COHORT Study

NCT04087239 | Active Not Recruiting

• 1 other identifier: MRCZ/A/1968
• Study Type: observational
• Target: 1,200
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background Commencement of lifelong highly active antiretroviral therapy (HAART) immediately after HIV diagnosis (option B+), for treatment of human immunodeficiency virus (HIV), has greatly improved maternal-infant health in sub Saharan Africa (SSA). However, this development has also dramatically increased the number of maternally HAART/HIV-exposed-uninfected (HEU) infants in areas of high HIV prevalence. Compared to their HIV-unexposed uninfected (HUU) counterparts, HEU infants show increased mortality, higher rates of adverse birth outcomes, infectious and non-communicable diseases and impaired growth, immune responses and neurodevelopment. Adverse clinical outcomes and their respective risk factors alongside associated biomarkers of HEU infants in SSA have been insufficiently characterized. Early exposure to HAART and HIV might be risk factors for the adverse outcomes in HEU infants but other potential risk factors and biomarkers remain understudied. Methods The University of Zimbabwe-College of Health Science birth cohort is a prospective cohort study of perinatal HIV and in utero HAART exposure throughout the breastfeeding period in the era of option B+. 600 HIV infected and 600 HIV uninfected pregnant women ≥20 weeks of gestation are being enrolled from four primary health centres in poor high-density residential areas of Harare. Clinical, socio-demographic/economic, nutritional and environmental data and bio-samples including maternal urine, stool, plasma, milk, cord blood, amniotic fluid as well as infant serum, dried blood spots and stool are being collected at enrolment, delivery and longitudinal follow-ups as mother-infant pairs from delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Infants are being assessed for congenital transmission of HIV, hepatitis B/C viruses, cytomegalovirus, syphilis, and growth, neurodevelopment, and immune-dysregulation. Sub-studies are addressing maternal-infant immunometabolomics, latent tuberculosis infection, dysbiosis of the gut microbiome and the effect of maternal stress thereof. The primary end point of this study is infant mortality until two years of age in HEU versus HUU infants. Secondary outcomes include HEU morbidity. Conclusion Our study will provide a comprehensive assessment of risk factors and associated biomarkers for adverse clinical outcomes for HEU infants and ultimately help developing strategies to mitigate effects of HIV, comorbidities and early life HAART exposure on pregnancy outcome and infant health. Trial registration number, date Key words: HIV, Option B+ highly active antiretroviral therapy (HAART), in utero exposure, breastfeeding, antenatal co-morbidities, immune dysfunction, microbiota, genomics, pregnancy outcomes, neurodevelopment infant health.

Conditions

HIV Infections; Immune Activation; Comorbidities

Keywords

HAART exposure; infant immune/metabolic dysregulation; gut dysbiosis; breastfeeding; CMV; HBV; Syphilis; malnutrition

Outcome Measures

Primary Outcomes (2)

• Number of infants deaths

  On HIV exposed and unexposed infants.

  Delivery, 28 day, one and two years

• Number of maternal death

  HIV infected and HIV uninfected mothers.

  two years

Secondary Outcomes (20)

• Number of hospitalised Infant morbidity

  Delivery, 28 days, 6 months, one and two years

• Number of sick clinic visits

  Delivery, 28 days, 6 months, one and two years

• Number of small for gestational age

  Birth

• Number of LBW and macrosomia

  Birth

• Number of microcephaly

  Birth

Other Outcomes (13)

• Prevalence of Maternal malnutrition in HIV+ and HIV-

  At enrollment and 24 months

• Maternal clinical biochemistry profiles

  At enrolment and 24 months

• Infant anaemia and atopic dermatitis

  6 weeks, 6 months and 24 months of age

Study Arms (1)

Pregnant women from >20 weeks gestation

1,200 pregnant women (600 HIV infected mothers and 600 HIV uninfected controls) at least 20 weeks gestation were enrolled from January 2016 to June 2019. Participants are being followed as mother-baby pairs at birth, within 10 days of life 6, 10, 14 24, 48, 72 and 96 weeks of age. At each visit clinical examinations are being used to assess health and the impact of environmental factors. In addition, questionnaires are administered and bio-samples for laboratory tests. The design of the study is non-interventional cohort but participants are being offered advice regarding health and hygiene.

Other: HIV

Interventions

HIV OTHER

Also known as: Highly active antiretroviral therapy (HAART)

Pregnant women from >20 weeks gestation

Eligibility Criteria

• Age: 15 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All pregnant women with a documented positive HIV status were encouraged to enrol in the study. For every HIV positive pregnant woman recruited, the 10th HIV negative women was recruited, accounting for the 12% HIV prevalence within this population. The pregnancy was dated by the standard way of using menstrual history together with first trimester ultrasound scan where available.

You may qualify if:

• Consenting pregnant woman of Bantu origin of ≥15 years of age, at least 20 weeks of gestation at enrolment and planning to deliver at any of the 4 study sites, Kuwadzana, Rujeko, Glenview or Budiriro. Mothers should be willing to be followed together with their babies from delivery, and willing to provide the required data and biological specimens in follow-up visits for two years.

You may not qualify if:

• Presence of severe maternal mental disorders.

Sponsors & Collaborators

• University of Zimbabwe: lead
• Insel Gruppe AG, University Hospital Bern: collaborator
• University of Hamburg-Eppendorf: collaborator
• University of Oxford: collaborator
• Wellcome Trust: collaborator
• University of Yaounde: collaborator
• University of Cape Town: collaborator
• Midlands State University, Zimbabwe: collaborator
• National Institute of Health Research, Zimbabwe: collaborator

Related Publications (23)

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  PMID: 25030058 BACKGROUND

• Estrella MM, Fine DM, Atta MG. Recent developments in HIV-related kidney disease. HIV Ther. 2010 Sep;4(5):589-603. doi: 10.2217/hiv.10.42.

  PMID: 21331321 BACKGROUND

• Smith J, Mushati P, Kurwa F, Mason P, Gregson S, Lopman B. Changing patterns of adult mortality as the HIV epidemic matures in Manicaland, eastern Zimbabwe. AIDS. 2007 Nov;21 Suppl 6:S81-6. doi: 10.1097/01.aids.0000299414.60022.1b.

  PMID: 18032943 RESULT

• Hargrove JW, Humphrey JH; ZVITAMBO Study Group. Mortality among HIV-positive postpartum women with high CD4 cell counts in Zimbabwe. AIDS. 2010 Jan 28;24(3):F11-4. doi: 10.1097/qad.0b013e328335749d.

  PMID: 20095074 RESULT

• Gumbo FZ, Duri K, Kandawasvika GQ, Kurewa NE, Mapingure MP, Munjoma MW, Rusakaniko S, Chirenje MZ, Stray-Pedersen B. Risk factors of HIV vertical transmission in a cohort of women under a PMTCT program at three peri-urban clinics in a resource-poor setting. J Perinatol. 2010 Nov;30(11):717-23. doi: 10.1038/jp.2010.31. Epub 2010 Mar 25.

  PMID: 20336078 RESULT

• Zijenah LS, Moulton LH, Iliff P, Nathoo K, Munjoma MW, Mutasa K, Malaba L, Zvandasara P, Ward BJ, Humphrey J; ZVITAMBO Study Group. Timing of mother-to-child transmission of HIV-1 and infant mortality in the first 6 months of life in Harare, Zimbabwe. AIDS. 2004 Jan 23;18(2):273-80. doi: 10.1097/00002030-200401230-00017.

  PMID: 15075545 RESULT

• Ticklay IM, Nathoo KJ, Siziya S, Brady JP. HIV infection in malnourished children in Harare, Zimbabwe. East Afr Med J. 1997 Apr;74(4):217-20.

  PMID: 9299820 RESULT

• Shepherd BL, Ferrand R, Munyati S, Folkard S, Boyd K, Bandason T, Jallow S, Rowland-Jones SL, Yindom LM. HLA Correlates of Long-Term Survival in Vertically Infected HIV-1-Positive Adolescents in Harare, Zimbabwe. AIDS Res Hum Retroviruses. 2015 May;31(5):504-7. doi: 10.1089/AID.2014.0338. Epub 2015 Feb 9.

  PMID: 25560566 RESULT

• Duri K, Gumbo FZ, Kristiansen KI, Kurewa NE, Mapingure MP, Rusakaniko S, Chirenje MZ, Muller F, Stray-Pedersen B. Antenatal HIV-1 RNA load and timing of mother to child transmission; a nested case-control study in a resource poor setting. Virol J. 2010 Aug 2;7:176. doi: 10.1186/1743-422X-7-176.

  PMID: 20678190 RESULT

• Kurewa EN, Gumbo FZ, Munjoma MW, Mapingure MP, Chirenje MZ, Rusakaniko S, Stray-Pedersen B. Effect of maternal HIV status on infant mortality: evidence from a 9-month follow-up of mothers and their infants in Zimbabwe. J Perinatol. 2010 Feb;30(2):88-92. doi: 10.1038/jp.2009.121. Epub 2009 Aug 20.

  PMID: 19693024 RESULT

• Shamu T, Chimbetete C, Shawarira-Bote S, Mudzviti T, Luthy R. Outcomes of an HIV cohort after a decade of comprehensive care at Newlands Clinic in Harare, Zimbabwe: TENART cohort. PLoS One. 2017 Oct 24;12(10):e0186726. doi: 10.1371/journal.pone.0186726. eCollection 2017.

  PMID: 29065149 RESULT

• le Roux SM, Abrams EJ, Donald KA, Brittain K, Phillips TK, Nguyen KK, Zerbe A, Kroon M, Myer L. Growth trajectories of breastfed HIV-exposed uninfected and HIV-unexposed children under conditions of universal maternal antiretroviral therapy: a prospective study. Lancet Child Adolesc Health. 2019 Apr;3(4):234-244. doi: 10.1016/S2352-4642(19)30007-0. Epub 2019 Feb 15.

  PMID: 30773459 RESULT

• McCoy SI, Fahey C, Buzdugan R, Mushavi A, Mahomva A, Padian NS, Cowan FM. Targeting elimination of mother-to-child HIV transmission efforts using geospatial analysis of mother-to-child HIV transmission in Zimbabwe. AIDS. 2016 Jul 17;30(11):1829-37. doi: 10.1097/QAD.0000000000001127.

  PMID: 27124895 RESULT

• Afran L, Garcia Knight M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. HIV-exposed uninfected children: a growing population with a vulnerable immune system? Clin Exp Immunol. 2014 Apr;176(1):11-22. doi: 10.1111/cei.12251.

  PMID: 24325737 RESULT

• Koyanagi A, Humphrey JH, Ntozini R, Nathoo K, Moulton LH, Iliff P, Mutasa K, Ruff A, Ward B; ZVITAMBO Study Group. Morbidity among human immunodeficiency virus-exposed but uninfected, human immunodeficiency virus-infected, and human immunodeficiency virus-unexposed infants in Zimbabwe before availability of highly active antiretroviral therapy. Pediatr Infect Dis J. 2011 Jan;30(1):45-51. doi: 10.1097/INF.0b013e3181ecbf7e.

  PMID: 21173675 RESULT

• Claudio CC, Patin RV, Palchetti CZ, Machado DM, Succi RC, Oliveira FL. Nutritional status and metabolic disorders in HIV-exposed uninfected prepubertal children. Nutrition. 2013 Jul-Aug;29(7-8):1020-3. doi: 10.1016/j.nut.2013.01.019.

  PMID: 23759262 RESULT

• Liu H, Ma Y, Su Y, Smith MK, Liu Y, Jin Y, Gu H, Wu J, Zhu L, Wang N. Emerging trends of HIV drug resistance in Chinese HIV-infected patients receiving first-line highly active antiretroviral therapy: a systematic review and meta-analysis. Clin Infect Dis. 2014 Nov 15;59(10):1495-502. doi: 10.1093/cid/ciu590. Epub 2014 Jul 22.

  PMID: 25053721 RESULT

• Hofer CB, Keiser O, Zwahlen M, Lustosa CS, Frota AC, de Oliveira RH, Abreu TF, Carvalho AW, Araujo LE, Egger M. In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-exposed Uninfected Children in Brazil. Pediatr Infect Dis J. 2016 Jan;35(1):71-7. doi: 10.1097/INF.0000000000000926.

  PMID: 26741583 RESULT

• Evans C, Humphrey JH, Ntozini R, Prendergast AJ. HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era. Front Immunol. 2016 Jun 6;7:190. doi: 10.3389/fimmu.2016.00190. eCollection 2016.

  PMID: 27375613 RESULT

• Duri K, Mapingure MP, Munjoma PT, Mazhandu AJ, Ncube P, Marere T, Ronald ML; UZ Birth Cohort Study Team. Maternal mortality ratio and deaths beyond 42 days up to 5-years post pregnancy in women living with HIV on life-long antiretroviral therapy in a resource limited setting. BMC Pregnancy Childbirth. 2025 Nov 28;25(1):1274. doi: 10.1186/s12884-025-08151-5.

  PMID: 41316067 DERIVED

• Duri K, Munjoma PT, Mataramvura H, Mazhandu AJ, Chandiwana P, Marere T, Gumbo FZ, Mazengera LR. Antenatal hepatitis B virus sero-prevalence, risk factors, pregnancy outcomes and vertical transmission rate within 24 months after birth in a high HIV prevalence setting. BMC Infect Dis. 2023 Oct 27;23(1):736. doi: 10.1186/s12879-023-08523-2.

  PMID: 37891471 DERIVED

• Zhang Z, Duri K, Duisters KLW, Schoeman JC, Chandiwana P, Lindenburg P, Jaeger J, Ziegler S, Altfeld M, Kohler I, Harms A, Gumbo FZ, Hankemeier T, Bunders MJ. Altered methionine-sulfone levels are associated with impaired growth in HIV-exposed-uninfected children. AIDS. 2023 Jul 15;37(9):1367-1376. doi: 10.1097/QAD.0000000000003574. Epub 2023 Apr 11.

  PMID: 37070556 DERIVED

• Duri K, Gumbo FZ, Munjoma PT, Chandiwana P, Mhandire K, Ziruma A, Macpherson A, Rusakaniko S, Gomo E, Misselwitz B, Mazengera LR; UZ-CHS Birth Cohort Team. The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods. BMC Infect Dis. 2020 Oct 2;20(1):725. doi: 10.1186/s12879-020-05432-6.

  PMID: 33008316 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

maternal urine, stool, plasma, milk, cord blood, amniotic fluid, placenta, infant serum/plasma, dried blood spots and stool

MeSH Terms

Conditions

HIV Infections; Breast Feeding; Syphilis; Malnutrition

Interventions

Antiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Feeding Behavior; Behavior; Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sexually Transmitted Diseases, Bacterial; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Study Officials

• Exnevia Gomo, PhD

  Research Support Centre/University of Zimbabwe

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: September 12, 2019
• Study Start: January 26, 2016
• Primary Completion: June 30, 2019
• Study Completion (Estimated): December 31, 2035
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: within after 10 years after completion of the study
• Access Criteria: Results will be published in journals with scientific quality assurance, and priority will be given to open access journals whenever possible. Published data will be made available to other researchers upon request and verification that additional use of data that goes beyond the studies proposed here is covered by the original approved study protocols and informed consent. The need for well -defined management and handling of research data is a priority both for national and international research organizations and for science may not over-emphasised