The University of Zimbabwe College of Health Science (UZ-CHS) BIRTH COHORT Study (UZ-CHS-BC)
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|ClinicalTrials.gov Identifier: NCT04087239|
Recruitment Status : Unknown
Verified November 2020 by Kerina Duri, University of Zimbabwe.
Recruitment status was: Active, not recruiting
First Posted : September 12, 2019
Last Update Posted : November 6, 2020
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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.
|Condition or disease||Intervention/treatment|
|HIV Infections Immune Activation Comorbidities||Other: HIV|
|Study Type :||Observational|
|Actual Enrollment :||1200 participants|
|Official Title:||HIV Exposure, Disease Acquisition and Progression Among Children: Role of Maternal Immunogenetics, Viral Genetic Diversity, HAART Exposure, Co-morbidities and Psycho-Social Status: (UZ-CHS Birth Cohort)|
|Actual Study Start Date :||January 26, 2016|
|Actual Primary Completion Date :||June 30, 2019|
|Estimated Study Completion Date :||June 30, 2021|
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 Name: Highly active antiretroviral therapy (HAART)
- Number of infants deaths [ Time Frame: Delivery, 28 day, one and two years ]On HIV exposed and unexposed infants.
- Number of maternal death [ Time Frame: two years ]HIV infected and HIV uninfected mothers.
- Number of hospitalised Infant morbidity [ Time Frame: Delivery, 28 days, 6 months, one and two years ]Comparison of morbidity of HEU vs. HUU infants, defined as impaired growth, immune- and neuro-development and/ or frequent clinically relevant infections
- Number of sick clinic visits [ Time Frame: Delivery, 28 days, 6 months, one and two years ]Comparison of morbidity of HEU vs. HUU infants, defined as impaired growth, immune- and neuro-development and/ or frequent clinically relevant infections
- Number of small for gestational age [ Time Frame: Birth ]To determine any association of maternal HIV infection, HAART exposure.
- Number of LBW and macrosomia [ Time Frame: Birth ]To determine any association with maternal HIV and HAART exposure.
- Number of microcephaly [ Time Frame: Birth ]To determine any association with maternal HIV and HAART exposure.
- Number of apgar score <7 [ Time Frame: Birth ]To determine any association with maternal HIV and HAART exposure.
- Infant physical growth [ Time Frame: 10 days, 6, 10, 14, 24, 36, 48, 72 and 96 weeks of age ]To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development.
- Proportion of stunted Infants [ Time Frame: 6, 10, 14, 24, 36, 48, 72 and 96 weeks of ag ]To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development.
- Proportion of wasted infants [ Time Frame: 6, 10, 14, 24, 36, 48, 72 and 96 weeks of age ]To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development.
- Number of Infant MUAC below mean 2 standard deviations [ Time Frame: 6, 10, 14, 24, 36, 48, 72 and 96 weeks of age ]To determine any association of HAART exposure in utero and during breast feeding with pregnancy outcome, infant (HUU, HEU, HEI) growth and immune- and neuro-development.
- Number HIV vertical transmission cases [ Time Frame: 10 day, 6, 24, 48 and 96 weeks ]To determine vertical transmission rates for HIV at birth and within the first 2 years of life and assess risk factors for transmission
- Maternal HIV incidence [ Time Frame: 24 months ]HIV incidence rate among mother sero-negative at enrollment
- HAART level in plasma, amniotic fluid and longitudinal breast milk sample [ Time Frame: From pregnancy, at delivery and every 6 months for 2 years ]To determine the association between maternal baseline and delivery HAART levels in different compartments and the relation of those to infant HIV transmission, mortality and morbidity.
- Level of maternal-infant plasma immune and metabolic dysfunction and in different duration of in utero HAART exposure [ Time Frame: From pregnancy, at delivery, 6, 10, 24, and every 6 months for 2 years ]To determine the association between antenatal immune dysregulation and infant death, growth and immune responses to vaccines.
- Frequency of mother -infant pairs HIV drug resistance profiles [ Time Frame: Earliest possible blood sample and at 24 months ]To determine HIV drug resistance profiles in mother and infants unresponsive to HAART
- Proportion of Maternal plasma ,amniotic fluid and breast milk CMV DNAemia [ Time Frame: In pregnancy , 10 days, 6, 10 , 14 and 24 weeks. ]To determine how CMV DNA is influenced by HIV infection, HAART use and as single infection or combined infections in HIV+ and HIV- women and determine the impact on pregnancy outcome and infant cmv vertical transmission
- Proportion of Maternal positive HBV markers of infection [ Time Frame: In pregnancy and 96 weeks ]To determine how HBV infection infections in HIV infected and HIV uninfected women and determine the impact on pregnancy outcome, infant vertical transmission
- Proportion of Maternal positive HCV antibodies [ Time Frame: In pregnancy 6, 24, 48 and 96 weeks ]To determine HCV infections proportion in HIV positives and negatives women
- Prevalence of antenatal syphilis sero-positivity [ Time Frame: In pregnancy 6, 24, 48 and 96 weeks ]To determine syphilis infections proportion in HIV positives and negatives and the impact on pregnancy outcome, infant incidence of congenital syphilis infection
- Prevalence of antenatal intestinal helminthes infection [ Time Frame: From birth , 6, 24, 48 and 96 weeks of age ]To determine the prevalence of helminthes infection using 18s sequencing and correlate with infant development of atopic dermatitis.
- Prevalence of Maternal malnutrition in HIV+ and HIV- [ Time Frame: At enrollment and 24 months ]To determine the prevalence of maternal under and overnutrition using BMI and MUAC impact on pregnancy outcomes, infant mortality and morbidity.
- Maternal clinical biochemistry profiles [ Time Frame: At enrolment and 24 months ]To assess abnormalities in HIV + and HIV- including lipid profiles, bone, haematological (anemia) and hepatic toxicities associated with exposure to HAART among mothers and infants.
- Infant anaemia and atopic dermatitis [ Time Frame: 6 weeks, 6 months and 24 months of age ]To determine infant non-infectious comorbidities (e.g. anaemia, atopic dermatitis, congenital infections and other conditions) and their impact on mortality and morbidity.
- Proportion of Infant abnormal /delayed neuro-cognitive development [ Time Frame: From 6 weeks,, 10, 14, 24, 36, 48, 96 weeks of age ]To assess delayed neuro-cognitive development using the Denver II tool in HUU, HEU and HEI infants and correlated with socio economic status and infectious diseases.
- Levels of infants humoural response to EPI vaccines [ Time Frame: 6, 48 and 96 weeks of age ]To determine humoural immune responses to EPI vaccines including antibody levels against measles, tetanus, diphtheria, pertussis, polio and rotavirus) in HUU, HEU and HEI infants.
- Infants immune activation and systemic inflammatory biomarkers levels [ Time Frame: Delivery, 6, 48 and 96 weeks of age. ]To determine immune activation and systemic inflammatory biomarkers in HUU, HEU and HEI infants
- Infant biomarkers of microbial translocation levels [ Time Frame: 6, 48 and 96 weeks of age ]To determine biomarkers for endothelial dysfunction including microbial translocation in HUU, HEU and HEI infants and association with household hygiene at delivery, 6, 48 and 96 weeks of age.
- Normal FBC and biochemistry ranges in pregnancy and after delivery [ Time Frame: Enrollment and 96 weeks. ]To determine antenatal reference ranges for MUAC, haemoglobin from FBC analyses, and biochemistry (kidney function, liver function tests, bone, lipid profiles) in mothers with a favourable outcome of pregnancy
- Maternal-infant 16s sequencing profiling [ Time Frame: Enrollment, delivery, 6 weeks and every 6 months. ]To determine maternal- infant microbiota16S sequencing in pregnancy and relate it to infant immune development and atopy (anti-inflammatory (IL-4, -5, -13) and regulatory cytokines (IL-10, TGF-β) at delivery, 6 weeks 48 and 96 weeks of age.
- In-depth maternal-infant microbiota analysis [ Time Frame: In pregnancy during breast feeding and after weaning ]Bacterial full genome metagenomics shotgun sequencing to identify the microbiota metabolic potential (i.e. bacterial genes present will be done) and mass spectrometry will be performed for analysis of small intestinal content (metabolome).
- In -depth human milk analysis, including, nutritional values, HAART levels, and herpes viruses and oligosaccharide profiles [ Time Frame: Enrollement, 6 weeks 24, 48 and 72 weeks. ]Wide range of nutritional profiles and HAART levels spectrometry will be performed for analysis of at least 700 metabolites including amino acids and lipids will be performed in plasma, breast milk and stool samples
- Viral genetic diversity and evolution [ Time Frame: At enrollment for mothers,earliest available sample for infants and at 2 years ]To characterize pathogen genetic diversity including HIV, HBV, HCV, CMV subtypes, prevalent in our study population at time of infection
- Host genetics profiling and trending [ Time Frame: At enrollment for mothers, earliest available sample for infants ]To determine host genetic markers for infectious disease susceptibility including human leukocyte antigen (HLA) and killer immunoglobulin like receptor (KIR) gene variants and their association with infection rates of HIV and co-infections in mothers and their infants.
Biospecimen Retention: Samples With DNA
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|Ages Eligible for Study:||15 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||Yes|
|Sampling Method:||Probability Sample|
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.
- Presence of severe maternal mental disorders.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04087239
|Study Chair:||Exnevia Gomo, PhD||Research Support Centre/University of Zimbabwe|
Documents provided by Kerina Duri, University of Zimbabwe:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Kerina Duri, Associate Professor, University of Zimbabwe|
|Other Study ID Numbers:||
|First Posted:||September 12, 2019 Key Record Dates|
|Last Update Posted:||November 6, 2020|
|Last Verified:||November 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Only anonymous data will be stored at local sites and transferred between sites for collaborative research efforts. All original data will be stored locally at the UZ-CHS for at least 10 years on suitable electronic devices. Data transfer with collaborating partners will be encrypted. using EGAcryptor. With our European partners we will follow the current European General Data Protection Regulation effective May 25, 2018.|
Informed Consent Form (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|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
infant immune/metabolic dysregulation
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
RNA Virus Infections
Immunologic Deficiency Syndromes
Immune System Diseases