Single-dose Postpartum Vitamin A Supplementation of Mothers and Neonates

HIV Clinical Trial

— ZVITAMBO  

Official title:

Vitamin A Supplementation of Breast Feeding Mothers and Their Neonates at Delivery: Impact on Mother to Child Transmission of HIV During Lactation, HIV Infection Among Women During the Postpartum Year, and Infant Mortality.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00198718
• Other study ID #: (CIDA) (R/C Project 690/M3688)
• Status: Completed
• Phase: Phase 2
• Start date: November 1997
• Est. completion date: December 31, 2020

Study information

• Verified date: October 2022
• Source: Johns Hopkins Bloomberg School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ZVITAMBO PROJECT is testing whether giving mothers and infants a single large dose of vitamin A during the immediate post partum period will reduce: 1. Infant Mortality Can oral administration of a single 50,000 IU dose of vitamin A to newborn infants, a single 400,000 IU dose of vitamin A given to their lactating mothers, or supplementation of both the mother and infant during the immediate post partum period reduce infant mortality by at least 30%? 2. Mother to Child HIV transmission during breast feeding Can oral administration of a single large dose of vitamin A given during the immediate post partum period to HIV seropositive lactating women and/or their babies reduce HIV transmission via breast feeding by at least 30%? 3. Sexually transmitted HIV infection of post partum women Can a single 400,000 IU dose of vitamin A given during the immediate post partum period to HIV seronegative women reduce their likelihood of becoming HIV infected during the post partum year by at least 25%? 4. Infant feeding in the context of HIV: An operational research study was initiated mid-way through the trial to determine how UNAIDS Guidelines on infant feeding in the context of HIV could be effectively implemented and to measure the impact of such a program on infant feeding practices and postnatal HIV transmission. Substudies: Random subsamples of maternal and infant blood were evaluated for anemia and iron status to determine the effect of vitamin A on hematopoiesis and serum and breast milk retinol (mothers) and modified relative dose response test (infants) to determine the effect of vitamin A on vitamin A status. A subsample of maternal and infant blood samples were evaluated for the presence of HLA-E, HLA-G, and TAP polymorphisms and their relation to prevalent HIV infection in mothers and risk of mother to child transmission.

Description:

The Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) project was a placebo-controlled randomized trial, which enrolled 14,110 mothers and their infants within 96 hours of delivery from one of 14 hospitals and clinics in greater Harare between November 25, 1997 and January 29, 2000. Mother-baby pairs were eligible if neither had an acutely life threatening condition, the baby was a singleton with birth weight >1500 g, and the mother planned to stay in Harare after delivery. Written informed consent was obtained from the mother. Socio-economic and demographic characteristics were collected by interview and obstetric details of the pregnancy and delivery were transcribed from hospital records. Gestational age was estimated. Infant birth weight was measured using an electronic scale. Infant length, infant head circumference, and maternal arm circumference were measured. Arm circumference was measured as an indicator of maternal nutritional status rather than Body Mass Index because it is less influenced by fluid fluctuations during the immediate post partum period. Addresses were recorded for the mother's urban and rural residences (it is common for urban Zimbabweans to travel frequently to extended family rural homesteads), her place of work, her husband's place of work, and that of relative who would always know her whereabouts. At recruitment, study nurses collected plasma and serum from mothers and babies. Maternal plasma was stored at room temperature (~20° C) and other samples in a cool box (~ 10-15° C) before being transferred to the laboratory within 2 hr of collection. Mother-baby pairs were randomized to one of four treatment groups: mother received 400,000 IU vitamin A (as retinyl palmitate) and baby received 50,000 IU vitamin A (Aa group); mother received 400,000 IU vitamin A and baby received placebo (Ap group); mother received placebo and baby received 50,000 IU vitamin A (Pa group); and both mother and baby received placebo (Pp group). Treatment and placebo capsules appeared identical and both contained a soy oil base with vitamin E as a preservative (50 IU per maternal capsule; 10 IU per infant capsule) (Tishcon Corporation, Westbury, NY, USA). A separate team at Johns Hopkins University prepared the study capsule packets. Study identification numbers were randomly allocated to the treatment groups by computer in blocks of 12. The numbers were printed on adhesive labels and affixed to amber-colored zip-lock plastic bags that were packed with the assigned capsules. Capsule packets were prepared separately for each of the four treatment groups, and then merged into numeric order before shipping to Zimbabwe where series of packets were distributed to each recruitment site. As each mother-baby pair was recruited, the capsules in the next sequential bag were administered, and the associated study number assigned to the pair. Lists linking the study number to the treatment were kept in sealed envelopes and encrypted computer files that were not accessible to the Zimbabwe-based study team. Pairs were followed at 6 wk, 3 mo, and then 3 monthly up to 24 months at one of three study clinics. Home visits were attempted for defaulting pairs to either their urban or rural home anywhere within the Zimbabwe borders. We initially planned to follow all HIV-positive mothers and their infants and a ~50% random sample of HIV-negative mothers and their infants for 24 months. However, in June 2000, economic conditions necessitated discontinuing the second year of follow up. This meant that 24%, 48% and 100% of the pairs were reassigned to 24 months, >18 month, and >12 month follow up, respectively. Follow up visits included assessment of recent illness, sick clinic visits, and hospitalizations by the mother or infant; anthropometric measures, infant dietary history, maternal sexual and reproductive health practices, and blood and breast milk sampling. Free clinical care included treatment of acute infections with appropriate antimicrobial drugs, referral to government treatment facilities for suspect tuberculosis, counseling and antibiotic treatment for mastitis, and oral rehydration solution education for diarrhea. HIV-related and psychosocial counseling was available throughout the study. For mothers and infants who died, cause of death was determined from medical records for infants who died in a hospital or from review of verbal autopsy information by a study pediatrician (infants) or study obstetrician (mothers), who were masked to treatment group, for infants dying at home. Multiple causes of death were permitted and were not ranked hierarchically, in keeping with the recommendations of an expert group convened by the World Health Organization. Maternal plasma were tested for HIV at baseline by two ELISA tests run in parallel, and by Western Blot when duplicate pairs of ELISA test results were discordant. Mothers who tested negative at baseline were retested for HIV at every blood sampling. Quality control was monitored by use of kits controls, inclusion of an internal QC sample on every plate, and participation in the quality assurance program for HIV testing of the Zimbabwe Ministry of Health. Serum retinol concentration was measured in a subsample of mothers and babies by HPLC; quality control was monitored by inclusion of standards provided by the National Institute of Standards and Technology (Gaithersburg, MD, USA) and participation in their quality assurance program Hemoglobin was measured for women enrolled from October 1, 1998 to the end of the study (about 60% of the total sample) by HemoCue (Mission Viejo, CA). Among mothers who were HIV-positive at recruitment, CD4 cells were enumerated within 48 hours of phlebotomy (Facscount, Becton Dickinson International, Erembodegem, Belgium), and viral load was measured in a subsample (Roche Amplicor HIV-1 Monitor test version 1.5, Roche Diagnostics, Alameda, CA, USA). Plasma and cell pellets were archived from HIV-exposed infants at all visits. After follow-up was completed, the last available specimen from each infant was tested (plasma by GeneScreen ELISA for samples collected ≥18 months; or cell pellets by Amplicor HIV -1 DNA test version 1.5 (Roche Diagnostic Systems) for samples collected <18 months). If this sample was HIV-negative, the infant was classified as negative; if it was HIV-positive, samples collected at younger ages were tested to determine timing of infection. Education and counseling about infant feeding in the context of HIV was updated throughout the trial. When the trial began, information about HIV transmission through breastfeeding was scanty. In June 1998, new infant feeding guidelines were published by UNAIDS/UNICEF/WHO stating that HIV-positive mothers should be fully informed about the risks and benefits of infant feeding alternatives and empowered to make their best personal choice. In response, we modified our procedures to provide 24-hour turn-around time for maternal HIV test results. Study nurses were trained to counsel HIV-positive women about feeding options and kitchens were established for teaching safe replacement feeding. Additional funding was obtained to conduct formative research to inform a more effective program to educate mothers about infant feeding in the context of HIV. This program included group education, incorporating infant feeding issues into individual counseling, and integrating mother to child HIV transmission issues into on-going work-site education programs targeting men, which were being run by other organizations in Harare. The program was fully implemented within the trial by November 1st 1999. It emphasized exclusive breastfeeding for HIV-positive mothers who chose to breastfeed, optimal breastfeeding techniques to avoid cracked nipples, milk stasis, and mastitis; prompt treatment of breast problems; and safe sex practices especially during the breastfeeding period. These four 'safer breastfeeding' practices were also promoted among all status-unknown and HIV negative women. Known HIV-positive women were counseled to stop breastfeeding early. All laboratory analyses and data management was conducted in Harare. The protocol and interim analyses were reviewed by an external data safety and monitoring committee. The study protocol was approved by the Medical Research Council of Zimbabwe, The Medicines Control Authority of Zimbabwe, The Johns Hopkins Bloomberg School of Public Health Committee on Human Research, and the Montreal General Hospital Ethics Committee.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28220
• Est. completion date: December 31, 2020
• Est. primary completion date: May 2001
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• mothers and their neonates delivering at a study recruitment site during the recruitment period

Exclusion Criteria:

• mother in intensive care unit
• mother not fully conscious
• maternal temperature > 39°
• Mother is 'nil per mouth' (NPO)
• Mother is terminally ill as indicated in medical notes
• Infant is NPO
• Infant is terminally ill as indicated in medical notes
• Infant birth weight <1500 g
• Infant is a twin or triplet delivery
• Regular place of residence is outside Harare.

Related Conditions & MeSH terms

• HIV
• Night Blindness
• Vitamin A Deficiency

Intervention

Drug:
• Vitamin A (retinyl palmitate)

Locations

Country	Name	City	State
n/a

Sponsors (10)

Lead Sponsor	Collaborator
Johns Hopkins Bloomberg School of Public Health	BASF, Bill and Melinda Gates Foundation, Harare City Health Department, Harare, Zimbabwe, McGill University Health Centre/Research Institute of the McGill University Health Centre, Rockefeller Foundation, SARA and Linkages Projects, Academy for Educational Development, Washington DC., United States Agency for International Development (USAID), Université de Montréal, University of Zimbabwe

References & Publications (57)

Boily-Larouche G, Iscache AL, Zijenah LS, Humphrey JH, Mouland AJ, Ward BJ, Roger M. Functional genetic variants in DC-SIGNR are associated with mother-to-child transmission of HIV-1. PLoS One. 2009 Oct 7;4(10):e7211. doi: 10.1371/journal.pone.0007211. — View Citation

Cowan FM, Humphrey JH, Ntozini R, Mutasa K, Morrow R, Iliff P. Maternal Herpes simplex virus type 2 infection, syphilis and risk of intra-partum transmission of HIV-1: results of a case control study. AIDS. 2008 Jan 11;22(2):193-201. — View Citation

Evans C, Chasekwa B, Ntozini R, Humphrey JH, Prendergast AJ. Head circumferences of children born to HIV-infected and HIV-uninfected mothers in Zimbabwe during the preantiretroviral therapy era. AIDS. 2016 Sep 24;30(15):2323-8. doi: 10.1097/QAD.0000000000001196. — View Citation

Evans C, Chasekwa B, Rukobo S, Govha M, Mutasa K, Ntozini R, Humphrey JH, Prendergast AJ. Cytomegalovirus Acquisition and Inflammation in Human Immunodeficiency Virus-Exposed Uninfected Zimbabwean Infants. J Infect Dis. 2017 Mar 1;215(5):698-702. doi: 10.1093/infdis/jiw630. — View Citation

Gough EK, Moodie EE, Prendergast AJ, Ntozini R, Moulton LH, Humphrey JH, Manges AR. Linear growth trajectories in Zimbabwean infants. Am J Clin Nutr. 2016 Dec;104(6):1616-1627. Epub 2016 Nov 2. — View Citation

Gumbo H, Chasekwa B, Church JA, Ntozini R, Mutasa K, Humphrey JH, Prendergast AJ. Congenital and postnatal CMV and EBV acquisition in HIV-infected Zimbabwean infants. PLoS One. 2014 Dec 18;9(12):e114870. doi: 10.1371/journal.pone.0114870. eCollection 2014. — View Citation

Hargrove J, Humphrey J; ZVITAMBO Study Group. Short communication: Simplified estimation of the long-term specificity of the BED assay to improve estimates of HIV incidence. AIDS Res Hum Retroviruses. 2010 Sep;26(9):977-9. doi: 10.1089/aid.2010.0009. — View Citation

Hargrove JW, Humphrey JH, Mahomva A, Williams BG, Chidawanyika H, Mutasa K, Marinda E, Mbizvo MT, Nathoo KJ, Iliff PJ, Mugurungi O; ZVITAMBO Study Group. Declining HIV prevalence and incidence in perinatal women in Harare, Zimbabwe. Epidemics. 2011 Jun;3(2):88-94. doi: 10.1016/j.epidem.2011.02.004. Epub 2011 Mar 2. — View Citation

Hargrove JW, Humphrey JH, Mutasa K, Parekh BS, McDougal JS, Ntozini R, Chidawanyika H, Moulton LH, Ward B, Nathoo K, Iliff PJ, Kopp E. Improved HIV-1 incidence estimates using the BED capture enzyme immunoassay. AIDS. 2008 Feb 19;22(4):511-8. doi: 10.1097/QAD.0b013e3282f2a960. — View Citation

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. — View Citation

Humphrey J, Iliff P. Is breast not best? Feeding babies born to HIV-positive mothers: bringing balance to a complex issue. Nutr Rev. 2001 Apr;59(4):119-27. Review. — View Citation

Humphrey JH and Ichord RN: Safety of vitamin A supplementation of postpartum women and young children. Food and Nutrition Bulletin (2001) 22: 311-319.

Humphrey JH, Hargrove JW, Malaba LC, Iliff PJ, Moulton LH, Mutasa K, Zvandasara P, Nathoo KJ, Mzengeza F, Chidawanyika H, Zijenah LS, Ward BJ; ZVITAMBO Study Group. HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation. AIDS. 2006 Jun 26;20(10):1437-46. — View Citation

Humphrey JH, Iliff PJ, Marinda ET, Mutasa K, Moulton LH, Chidawanyika H, Ward BJ, Nathoo KJ, Malaba LC, Zijenah LS, Zvandasara P, Ntozini R, Mzengeza F, Mahomva AI, Ruff AJ, Mbizvo MT, Zunguza CD; ZVITAMBO Study Group. Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality. J Infect Dis. 2006 Mar 15;193(6):860-71. Epub 2006 Feb 8. Erratum in: J Infect Dis. 2008 May 15;197(10):1485. — View Citation

Humphrey JH, Marinda E, Mutasa K, Moulton LH, Iliff PJ, Ntozini R, Chidawanyika H, Nathoo KJ, Tavengwa N, Jenkins A, Piwoz EG, Van de Perre P, Ward BJ; ZVITAMBO study group. Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study. BMJ. 2010 Dec 22;341:c6580. doi: 10.1136/bmj.c6580. — View Citation

Humphrey JH, Nathoo KJ, Hargrove JW, Iliff PJ, Mutasa KE, Moulton LH, Chidawanyika H, Malaba LC, Zijenah LS, Zvandasara P, Ntozini R, Zunguza CD, Ward BJ; ZVITAMBO Study Group. HIV-1 and HIV-2 prevalence and associated risk factors among postnatal women in Harare, Zimbabwe. Epidemiol Infect. 2007 Aug;135(6):933-42. Epub 2007 Jan 12. — View Citation

Humphrey JH, Quinn T, Fine D, Lederman H, Yamini-Roodsari S, Wu LS, Moeller S, Ruff AJ. Short-term effects of large-dose vitamin A supplementation on viral load and immune response in HIV-infected women. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Jan 1;20(1):44-51. — View Citation

Humphrey JH, Rice AL. Vitamin A supplementation of young infants. Lancet. 2000 Jul 29;356(9227):422-4. — View Citation

Iliff P, Ntozini R, Nathoo K, Piwoz E, Moulton L; ZVITAMBO Study Group, Humphrey J. Making a working clinical diagnosis of HIV infection in infants in Zimbabwe. Trop Med Int Health. 2008 Dec;13(12):1459-69. doi: 10.1111/j.1365-3156.2008.02178.x. — View Citation

Iliff PJ, Humphrey JH, Mahomva AI, Zvandasara P, Bonduelle M, Malaba LC, Nathoo KJ. Tolerance of large doses of vitamin A given to mothers and their babies shortly after delivery. Nutr Res 1999; 19 (10): 1437-1446.

Iliff PJ, Piwoz EG, Tavengwa NV, Zunguza CD, Marinda ET, Nathoo KJ, Moulton LH, Ward BJ, Humphrey JH; ZVITAMBO study group. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS. 2005 Apr 29;1 — View Citation

Kirkwood B, Humphrey J, Moulton L, Martines J. Neonatal vitamin A supplementation and infant survival. Lancet. 2010 Nov 13;376(9753):1643-4. doi: 10.1016/S0140-6736(10)61895-8. Epub 2010 Oct 13. — View Citation

Koyanagi A, Humphrey JH, Moulton LH, Ntozini R, Mutasa K, Iliff P, Black RE. Effect of early exclusive breastfeeding on morbidity among infants born to HIV-negative mothers in Zimbabwe. Am J Clin Nutr. 2009 May;89(5):1375-82. doi: 10.3945/ajcn.2008.26810. Epub 2009 Apr 1. — View Citation

Koyanagi A, Humphrey JH, Moulton LH, Ntozini R, Mutasa K, Iliff P, Ruff AJ; Zvitambo Study Group. Predictive value of weight loss on mortality of HIV-positive mothers in a prolonged breastfeeding setting. AIDS Res Hum Retroviruses. 2011 Nov;27(11):1141-8. doi: 10.1089/AID.2010.0293. Epub 2011 Feb 16. — View Citation

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. — View Citation

Koyanagi A, Ruff AJ, Moulton LH, Ntozini R, Mutasa K, Iliff P, Humphrey JH; ZVITAMBO Study Group. Postpartum plasma CD4 change in HIV-positive women: implications for timing of HAART initiation. AIDS Res Hum Retroviruses. 2010 May;26(5):547-52. doi: 10.1089/aid.2009.0138. — View Citation

Lajoie J, Hargrove J, Zijenah LS, Humphrey JH, Ward BJ, Roger M. Genetic variants in nonclassical major histocompatibility complex class I human leukocyte antigen (HLA)-E and HLA-G molecules are associated with susceptibility to heterosexual acquisition of HIV-1. J Infect Dis. 2006 Jan 15;193(2):298-301. Epub 2005 Dec 1. — View Citation

Lajoie J, Zijenah LS, Faucher MC, Ward BJ, Roger M; ZVITAMBO Study Group. New transporter associated with antigen processing (TAP-2) polymorphisms in the Shona people of Zimbabwe. Hum Immunol. 2003 Jul;64(7):733-40. — View Citation

Lajoie J, Zijenah LS, Faucher MC, Ward BJ, Roger M; ZVITAMBO Study Group. Novel TAP1 polymorphisms in indigenous Zimbabweans: their potential implications on TAP function and in human diseases. Hum Immunol. 2003 Aug;64(8):823-9. — View Citation

Lunney KM, Iliff P, Mutasa K, Ntozini R, Magder LS, Moulton LH, Humphrey JH. Associations between breast milk viral load, mastitis, exclusive breast-feeding, and postnatal transmission of HIV. Clin Infect Dis. 2010 Mar 1;50(5):762-9. doi: 10.1086/650535. — View Citation

Lunney KM, Jenkins AL, Tavengwa NV, Majo F, Chidhanguro D, Iliff P, Strickland GT, Piwoz E, Iannotti L, Humphrey JH. HIV-positive poor women may stop breast-feeding early to protect their infants from HIV infection although available replacement diets are grossly inadequate. J Nutr. 2008 Feb;138(2):351-7. — View Citation

Malaba LC, Iliff PJ, Nathoo KJ, Marinda E, Moulton LH, Zijenah LS, Zvandasara P, Ward BJ, Humphrey JH; ZVITAMBO Study Group. Effect of postpartum maternal or neonatal vitamin A supplementation on infant mortality among infants born to HIV-negative mothers — View Citation

Marinda E, Humphrey JH, Iliff PJ, Mutasa K, Nathoo KJ, Piwoz EG, Moulton LH, Salama P, Ward BJ; ZVITAMBO Study Group. Child mortality according to maternal and infant HIV status in Zimbabwe. Pediatr Infect Dis J. 2007 Jun;26(6):519-26. — View Citation

Marinda ET, Moulton LH, Humphrey JH, Hargrove JW, Ntozini R, Mutasa K, Levin J. In utero and intra-partum HIV-1 transmission and acute HIV-1 infection during pregnancy: using the BED capture enzyme-immunoassay as a surrogate marker for acute infection. Int J Epidemiol. 2011 Aug;40(4):945-54. doi: 10.1093/ije/dyr055. Epub 2011 Apr 5. — View Citation

Matte C, Lacaille J, Zijenah L, Ward B, Roger M. HLA-G and HLA-E polymorphisms in an indigenous African population. The ZVITAMBO Study Group. Hum Immunol. 2000 Nov;61(11):1150-6. — View Citation

Matte C, Lacaille J, Zijenah L, Ward B, Roger M; ZVITAMBO Study Group. HLA-G exhibits low level of polymorphism in indigenous East Africans. Hum Immunol. 2002 Jun;63(6):495-501. — View Citation

Miller M, Humphrey J, Johnson E, Marinda E, Brookmeyer R, Katz J. Why do children become vitamin A deficient? J Nutr. 2002 Sep;132(9 Suppl):2867S-2880S. doi: 10.1093/jn/132.9.2867S. — View Citation

Miller M, Iliff P, Stoltzfus RJ, Humphrey J. Breastmilk erythropoietin and mother-to-child HIV transmission through breastmilk. Lancet. 2002 Oct 19;360(9341):1246-8. — View Citation

Miller MF, Humphrey JH, Iliff PJ, Malaba LC, Mbuya NV, Stoltzfus RJ; ZVITAMBO Study Group. Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study. BMC Infect Dis. 2006 Jan 3;6:1. — View Citation

Miller MF, Stoltzfus RJ, Iliff PJ, Malaba LC, Mbuya NV; Zimbabwe Vitamin A for Mothers and Babies Project (ZVITAMBO) Study Group, Humphrey JH. Effect of maternal and neonatal vitamin A supplementation and other postnatal factors on anemia in Zimbabwean infants: a prospective, randomized study. Am J Clin Nutr. 2006 Jul;84(1):212-22. — View Citation

Miller MF, Stoltzfus RJ, Mbuya NV, Malaba LC, Iliff PJ, Humphrey JH; ZVITAMBO Study Group. Total body iron in HIV-positive and HIV-negative Zimbabwean newborns strongly predicts anemia throughout infancy and is predicted by maternal hemoglobin concentrati — View Citation

Mupfudze TG, Stoltzfus RJ, Rukobo S, Moulton LH, Humphrey JH, Prendergast AJ; SHINE Trial Team, Jones AD, Manges A, Mangwadu G, Maluccio JA, Mbuya MN, Ntozini R, Tielsch JM. Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants. PLoS One. 2015 Aug 7;10(8):e0135227. doi: 10.1371/journal.pone.0135227. eCollection 2015. — View Citation

Mutasa K, Ntozini R, Prendergast A, Iliff P, Rukobo S, Moulton LH, Ward BJ, Humphrey JH; ZVITAMBO Study Group. Impact of six-week viral load on mortality in HIV-infected Zimbabwean infants. Pediatr Infect Dis J. 2012 Sep;31(9):948-50. — View Citation

Omoni AO, Ntozini R, Evans C, Prendergast AJ, Moulton LH, Christian PS, Humphrey JH. Child Growth According to Maternal and Child HIV Status in Zimbabwe. Pediatr Infect Dis J. 2017 Sep;36(9):869-876. doi: 10.1097/INF.0000000000001574. — View Citation

Piwoz EG, Humphrey JH, Marinda ET, Mutasa K, Moulton LH, Iliff PJ. Effects of infant sex on mother-to-child transmission of HIV-1 according to timing of infection in Zimbabwe. AIDS. 2006 Oct 3;20(15):1981-4. — View Citation

Piwoz EG, Humphrey JH, Tavengwa NV, Iliff PJ, Marinda ET, Zunguza CD, Nathoo KJ, Mutasa K, Moulton LH, Ward BJ. The impact of safer breastfeeding practices on postnatal HIV-1 transmission in Zimbabwe. Am J Public Health. 2007 Jul;97(7):1249-54. Epub 2007 May 30. — View Citation

Piwoz EG, Iliff PJ, Tavengwa N, Gavin L, Marinda E, Lunney K, Zunguza C, Nathoo KJ, Humphrey JH. An education and counseling program for preventing breast-feeding-associated HIV transmission in Zimbabwe: design and impact on maternal knowledge and behavio — View Citation

Rawat R, Humphrey JH, Mutasa K, Ntozini R, Stoltzfus RJ. Short communication: predicting adverse HIV-related outcomes in a resource-limited setting: use of the inflammation marker a(1)-acid glycoprotein. AIDS Res Hum Retroviruses. 2010 Nov;26(11):1171-4. doi: 10.1089/aid.2010.0053. Epub 2010 Oct 26. — View Citation

Rawat R, Humphrey JH, Ntozini R, Mutasa K, Iliff PJ, Stoltzfus RJ. Elevated iron stores are associated with HIV disease severity and mortality among postpartum women in Zimbabwe. Public Health Nutr. 2009 Sep;12(9):1321-9. doi: 10.1017/S136898000800390X. Epub 2008 Nov 12. — View Citation

Rawat R, Stoltzfus RJ, Ntozini R, Mutasa K, Iliff PJ, Humphrey JH. Influence of inflammation as measured by alpha-1-acid glycoprotein on iron status indicators among HIV-positive postpartum Zimbabwean women. Eur J Clin Nutr. 2009 Jun;63(6):787-93. doi: 10.1038/ejcn.2008.33. Epub 2008 May 28. — View Citation

Rollins N, Meda N, Becquet R, Coutsoudis A, Humphrey J, Jeffrey B, Kanshana S, Kuhn L, Leroy V, Mbori-Ngacha D, McIntyre J, Newell ML; Ghent IAS Working Group on HIV in Women and Children. Preventing postnatal transmission of HIV-1 through breast-feeding: modifying infant feeding practices. J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):188-95. Review. — View Citation

Stoltzfus RJ, Humphrey JH. Vitamin A and the nursing mother-infant dyad: evidence for intervention. Adv Exp Med Biol. 2002;503:39-47. Review. — View Citation

Tavengwa NV, Piwoz EG, Iliff PJ, Moulton LH, Zunguza CD, Nathoo KJ, Hargrove JW; ZVITAMBO Study Group, Humphrey JH. Adoption of safer infant feeding and postpartum sexual practices and their relationship to maternal HIV status and risk of acquiring HIV in Zimbabwe. Trop Med Int Health. 2007 Jan;12(1):97-106. — View Citation

Williams BG, Hargrove JW, Humphrey JH. The benefits of early treatment for HIV. AIDS. 2010 Jul 17;24(11):1790-1. doi: 10.1097/QAD.0b013e32833ac860. — View Citation

Zijenah LS, Humphrey J, Nathoo K, Malaba L, Zvandasara P, Mahomva A, Iliff P, Mbizvo MT. Evaluation of the prototype Roche DNA amplification kit incorporating the new SSK145 and SKCC1B primers in detection of human immunodeficiency virus type 1 DNA in Zim — View Citation

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. AID — View Citation

Zvandasara P, Hargrove JW, Ntozini R, Chidawanyika H, Mutasa K, Iliff PJ, Moulton LH, Mzengeza F, Malaba LC, Ward BJ, Nathoo KJ, Zijenah LS, Mbizvo M, Zunguza C, Humphrey JH; ZVITAMBO Study Group. Mortality and morbidity among postpartum HIV-positive and HIV-negative women in Zimbabwe: risk factors, causes, and impact of single-dose postpartum vitamin A supplementation. J Acquir Immune Defic Syndr. 2006 Sep;43(1):107-16. — View Citation

* Note: There are 57 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. HIV infection rate among baseline HIV-negative babies born to HIV-positive mothers at 24 months		By 24 months of age
Primary	2. Infant mortality rate among all infants, infants born to HIV-negative mothers, and infants born to HIV-positive mothers at 6 months		by 12 months of age
Primary	3. HIV infection rates among baseline HIV-negative mothers at 24 months		by 24 months postpartum
Secondary	1. HIV infection or death rate among baseline HIV-negative babies born to HIV-positive mothers at 6, 12, and 18 months		By 24 months of age
Secondary	2. HIV infection or death rate among 6-wk HIV-negative babies born to HIV-positive mothers at 6, 12, 18, 24 months		by 24 months of age
Secondary	3. Serum and breast milk retinol concentration among women at 12 months		12 months postpartum
Secondary	4. Modified relative dose response ratios among infants at 6 wk, and 3, 6, 9, and 12 months.		12 months post partum
Secondary	5. Viral load among HIV-positive women at 6 wk, and 3, 6, 9, and 12 months.		12 months postpartum
Secondary	6. Weight for age among infants at 12 months		12 months of age
Secondary	7. Weight for length among infants at 12 months		12 months of age
Secondary	8. Length for age among infants at 12 months		12 months of age