SHORT BREASTFEEDING AND COTRIMOXAZOLE AMONG HIV-EXPOSED INFANTS IN BOTSWANA
Roger L Shapiro
Harvard University (sch Of Public Hlth), Public Health Campus, Boston, Ma 02115
Grant 1R01HD061265-01A2 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Priorities for improving infant HIV-free survival in the developing world include preventing late mother-to-child HIV transmission (MTCT) during breastfeeding (BF) and reducing infant mortality after weaning. We hypothesize that cotrimoxazole (CTX) prophylaxis may reduce mortality among HIV-exposed but uninfected infants, particularly early in life for formula fed (FF) infants and after weaning in BF infants. CTX may therefore allow feeding strategies that reduce the period of BF and minimize MTCT risk. The proposed study is a randomized, double-blinded, placebo-controlled trial among 3,308 mother/infant pairs. The trial will compare survival (and HIV-free survival) at 12 months among infants receiving CTX vs. placebo from 4 weeks through 12 months. Feeding strategy will be observational, and the CTX vs. placebo randomization will be balanced across feeding methods. Supported feeding options will include exclusive BF + infant nevirapine prophylaxis for up to 3 months, exclusive BF + maternal HAART (if available) for up to 6 months, or FF from birth. The primary endpoint will be survival at 12 months by CTX or placebo arm. Secondary endpoints will evaluate survival and morbidity/mortality at 18 months; safety of CTX prophylaxis; survival (and HIV-free survival) between CTX/placebo arms by feeding method; MTCT by chosen feeding method at 1, 3, 6, and 12 months; survival with early vs. later weaning; and an analysis of maternal characteristics as predictors for feeding choice and HIV-free survival. All mothers and infants will receive antenatal and peripartum standard of care prophylaxis from the Botswana Government to prevent MTCT. HAART and CTX will be available from the Botswana Government for all qualifying HIV-infected women and infants. The competing risks of increased mortality from formula feeding and HIV transmission from breastfeeding remain one of the central dilemmas for early childhood survival in HIV-affected regions of the developing world. We hypothesize that in developing regions where formula feeding or early weaning are already common, the ideal balance for reducing both mother-to-child HIV transmission and infant mortality during infancy may be a short period of breastfeeding with infant nevirapine prophylaxis followed by formula feeding and infant prophylaxis with cotrimoxazole. If proven effective, these simple interventions -- used in the novel manner proposed in this randomized study -- could be combined to optimize HIV-free infant survival throughout much of the developing world
Keywords: 0-11 years old; 21+ years old; 6H-Dipyrido(3, 2-b[{..}]2`, 3`-e)(1, 4)diazepin-6-one, 11-cyclopropyl-5, 11-dihydro-4-methyl-; AIDS Virus; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Adult; Adverse Experience; Adverse event; Affect; Africa; Age; Age-Months; Anemia; Anti-Retroviral Agents; Antiretroviral Agents; Antiretroviral Therapy, Highly Active; Baby Formula; Bechuanaland; Birth; Botswana; Breast Feeding; Breastfeeding; Breastfeeding, Exclusive; Characteristics; Child; Child Youth; Children (0-21); Co-Trimoxazole; Co-Trimoxazole (Bactrim DS); Cotrimoxazole; Counseling; Data; Developing Countries; Developing Nations; District Hospitals; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Enrollment; Equilibrium; Event; Exclusive Breast Feeding; Exclusive Breastfeeding; Feeding Methods; Generalized Growth; Goals; Government; Growth; HAART; HIV; HIV Infections; HIV-1; HIV-I; HIV1; HOSP; HTLV-III; HTLV-III Infections; HTLV-III-LAV Infections; Hematology; Highly Active Antiretroviral Therapy; Hospitalization; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human immunodeficiency virus 1; Human, Adult; Human, Child; Immunodeficiency Virus Type 1, Human; Individual; Infant; Infant Mortality; Infant Mortality Total; Infant formula; Intervention; Intervention Strategies; Intervention Studies; LAV-HTLV-III; Less-Developed Countries; Less-Developed Nations; Life; Lymphadenopathy-Associated Virus; Measures; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Mothers; Neutropenia; Nevirapine; Outcome; PBO; Parturition; Perinatal; Placebos; Postneonatal Mortality; Pregnant Women; Prevention; Prevention Measures; Prophylactic treatment; Prophylaxis; Qualifying; Randomized; Research Design; Research Specimen; Resistance; Risk; Safety; Sham Treatment; Specimen; Study Type; Survival Rate; T-Lymphotropic Virus Type III Infections, Human; Third-World Countries; Third-World Nations; Time; Tissue Growth; Toxic effect; Toxicities; Transmission; Under-Developed Countries; Under-Developed Nations; Vertical Disease Transmission; Vertical Transmission; Viramune; Virus-HIV; WHO; Weaning; Woman; World Health Organization; ing; adult human (21+); adverse outcome; anti-retroviral; anti-retroviral therapy, highly active; antiretroviral; arm; balance; balance function; base; children; clinical significance; clinically significant; cohort; double-blind placebo controlled trial; double-masked controlled study; double-masked controlled trial; early childhood; enroll; feeding; high risk; human T cell leukemia virus III; human T lymphotropic virus III; improved; infancy; infantile; interventional strategy; meetings; mother to child transmission; novel; ontogeny; pathogen; postnatal; pregnant; prevent; preventing; prophylactic; public health relevance; randomisation; randomization; randomized placebo controlled study; randomized placebo controlled trial; randomized trial; randomly assigned; resistant; respiratory; sham therapy; standard of care; study design; transmission process; trial comparing; youngster
Relevance: The competing risks of increased mortality from formula feeding and HIV transmission from breastfeeding remain one of the central dilemmas for early childhood survival in HIV-affected regions of the developing world. We hypothesize that in developing regions where formula feeding or early weaning are already common, the ideal balance for reducing both mother-to-child HIV transmission and infant mortality during infancy may be a short period of breastfeeding with infant nevirapine prophylaxis followed by formula feeding and infant prophylaxis with cotrimoxazole. If proven effective, these simple interventions -- used in the novel manner proposed in this randomized study -- could be combined to optimize HIV-free infant survival throughout much of the developing world
Project start date: 2010-09-17
Project end date: 2015-06-30
Budget start date: 17-SEP-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-07-070
1R01HD061265-01A2 (2010): $513609
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Roger L Shapiro
SHORT BREASTFEEDING AND COTRIMOXAZOLE AMONG HIV-EXPOSED INFANTS IN BOTSWANA
Roger L Shapiro
Harvard University (sch Of Public Hlth), Public Health Campus, Boston, Ma 02115
Grant 3R01HD061265-01A2S1 from National Institute Of Allergy And Infectious Diseases
Abstract: Priorities for improving infant HIV-free survival in the developing world include preventing late mother-to-child HIV transmission (MTCT) during breastfeeding (BF) and reducing infant mortality after weaning. We hypothesize that cotrimoxazole (CTX) prophylaxis may reduce mortality among HIV-exposed but uninfected infants, particularly early in life for formula fed (FF) infants and after weaning in BF infants. CTX may therefore allow feeding strategies that reduce the period of BF and minimize MTCT risk. The proposed study is a randomized, double-blinded, placebo-controlled trial among 3,308 mother/infant pairs. The trial will compare survival (and HIV-free survival) at 12 months among infants receiving CTX vs. placebo from 4 weeks through 12 months. Feeding strategy will be observational, and the CTX vs. placebo randomization will be balanced across feeding methods. Supported feeding options will include exclusive BF + infant nevirapine prophylaxis for up to 3 months, exclusive BF + maternal HAART (if available) for up to 6 months, or FF from birth. The primary endpoint will be survival at 12 months by CTX or placebo arm. Secondary endpoints will evaluate survival and morbidity/mortality at 18 months; safety of CTX prophylaxis; survival (and HIV-free survival) between CTX/placebo arms by feeding method; MTCT by chosen feeding method at 1, 3, 6, and 12 months; survival with early vs. later weaning; and an analysis of maternal characteristics as predictors for feeding choice and HIV-free survival. All mothers and infants will receive antenatal and peripartum standard of care prophylaxis from the Botswana Government to prevent MTCT. HAART and CTX will be available from the Botswana Government for all qualifying HIV-infected women and infants. The competing risks of increased mortality from formula feeding and HIV transmission from breastfeeding remain one of the central dilemmas for early childhood survival in HIV-affected regions of the developing world. We hypothesize that in developing regions where formula feeding or early weaning are already common, the ideal balance for reducing both mother-to-child HIV transmission and infant mortality during infancy may be a short period of breastfeeding with infant nevirapine prophylaxis followed by formula feeding and infant prophylaxis with cotrimoxazole. If proven effective, these simple interventions -- used in the novel manner proposed in this randomized study -- could be combined to optimize HIV-free infant survival throughout much of the developing world
Keywords: 0-11 years old; 21+ years old; 6H-Dipyrido(3, 2-b[{..}]2`, 3`-e)(1, 4)diazepin-6-one, 11-cyclopropyl-5, 11-dihydro-4-methyl-; AIDS Virus; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Adult; Adverse Experience; Adverse event; Affect; Africa; Age; Age-Months; Anemia; Anti-Retroviral Agents; Antiretroviral Agents; Antiretroviral Therapy, Highly Active; Baby Formula; Bechuanaland; Birth; Botswana; Breast Feeding; Breastfeeding; Breastfeeding, Exclusive; Characteristics; Child; Child Youth; Children (0-21); Co-Trimoxazole; Co-Trimoxazole (Bactrim DS); Cotrimoxazole; Counseling; Data; Developing Countries; Developing Nations; District Hospitals; Double-Blind Method; Double-Blind Study; Double-Blinded; Double-Masked Method; Double-Masked Study; Enrollment; Equilibrium; Event; Exclusive Breast Feeding; Exclusive Breastfeeding; Feeding Methods; Generalized Growth; Goals; Government; Growth; HAART; HIV; HIV Infections; HIV-1; HIV-I; HIV1; HOSP; HTLV-III; HTLV-III Infections; HTLV-III-LAV Infections; Hematology; Highly Active Antiretroviral Therapy; Hospitalization; Human Immunodeficiency Viruses; Human T-Cell Leukemia Virus Type III; Human T-Cell Lymphotropic Virus Type III; Human T-Lymphotropic Virus Type III; Human immunodeficiency virus 1; Human, Adult; Human, Child; Immunodeficiency Virus Type 1, Human; Individual; Infant; Infant Mortality; Infant Mortality Total; Infant formula; Intervention; Intervention Strategies; Intervention Studies; LAV-HTLV-III; Less-Developed Countries; Less-Developed Nations; Life; Lymphadenopathy-Associated Virus; Measures; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Mothers; Neutropenia; Nevirapine; Outcome; PBO; Parturition; Perinatal; Placebos; Postneonatal Mortality; Pregnant Women; Prevention; Prevention Measures; Prophylactic treatment; Prophylaxis; Qualifying; Randomized; Research Design; Research Specimen; Resistance; Risk; Safety; Sham Treatment; Specimen; Study Type; Survival Rate; T-Lymphotropic Virus Type III Infections, Human; Third-World Countries; Third-World Nations; Time; Tissue Growth; Toxic effect; Toxicities; Transmission; Under-Developed Countries; Under-Developed Nations; Vertical Disease Transmission; Vertical Transmission; Viramune; Virus-HIV; WHO; Weaning; Woman; World Health Organization; ing; adult human (21+); adverse outcome; anti-retroviral; anti-retroviral therapy, highly active; antiretroviral; arm; balance; balance function; base; children; clinical significance; clinically significant; cohort; double-blind placebo controlled trial; double-masked controlled study; double-masked controlled trial; early childhood; enroll; feeding; high risk; human T cell leukemia virus III; human T lymphotropic virus III; improved; infancy; infantile; interventional strategy; meetings; mother to child transmission; novel; ontogeny; pathogen; postnatal; pregnant; prevent; preventing; prophylactic; public health relevance; randomisation; randomization; randomized placebo controlled study; randomized placebo controlled trial; randomized trial; randomly assigned; resistant; respiratory; sham therapy; standard of care; study design; transmission process; trial comparing; youngster
Relevance: The competing risks of increased mortality from formula feeding and HIV transmission from breastfeeding remain one of the central dilemmas for early childhood survival in HIV-affected regions of the developing world. We hypothesize that in developing regions where formula feeding or early weaning are already common, the ideal balance for reducing both mother-to-child HIV transmission and infant mortality during infancy may be a short period of breastfeeding with infant nevirapine prophylaxis followed by formula feeding and infant prophylaxis with cotrimoxazole. If proven effective, these simple interventions -- used in the novel manner proposed in this randomized study -- could be combined to optimize HIV-free infant survival throughout much of the developing world
Project start date: 2010-09-16
Project end date: 2015-06-30
Budget start date: 24-SEP-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-07-070
3R01HD061265-01A2S1 (2010): $131499
HAART TO PREVENT HIV TRANSMISSION TO INFANTS IN BOTSWANA
Roger L Shapiro, Assistant Professor
Harvard University (sch Of Public Hlth), Public Health Campus, Boston, Ma 02115
Grant 5U01AI066454-06 from National Institute Of Allergy And Infectious Diseases
Abstract: Highly active antiretroviral therapy (HAART) is rapidly becoming available in the developing world, but the safety and efficacy of different HAART regimens for preventing mother-to-child HIV transmission (MTCT) in a breastfeeding population has not been determined. To test our hypothesis that Trizivir (TZV) may be a simple, safe, and effective strategy to prevent MTCT (PMTCT) in Botswana, 560 pregnant women who intend to breastfeed their infants, and who have CD4 cell counts > 200 cells/mm3, will be randomized to receive TZV vs. Lopinavir/Ritonavir (LPV/RTV, or Kaletra)/Combivir (CBV) from 20-34 weeks of pregnancy through 6 months postpartum. An additional group of -140 women with baseline CD4 counts < 200 cells/mm3 will receive Nevirapine (NVP)/CBV for treatment, continued indefinitely. All infants will receive single dose (SD) NVP and 1 month of zidovudine (ZDV) prophylaxis. Women will discontinue HAART at 6 months postpartum, or at cessation of breastfeeding if this occurs earlier. If HAART is required for a woman´s own health, it will be continued indefinitely with NVP/CBV through the Botswana government´s Antiretroviral (ARV) Treatment Program. Women and infants will be followed in the study until infants reach 12 months of age. We believe TZV may perform well when used for PMTCT, and we will determine virologic outcomes by randomization arm to test this hypothesis. We also believe rates of antepartum, intrapartum, and breastfeeding MTCT will be low, and these will be determined among all infants in the randomized study, and among those born to women with CD4 counts < 200 cells/mm3 receiving NVP/CBV. Comparison of MTCT rates will be made with a group of infants who received an alternate non-HAART PMTCT strategy in a clinical trial at the same clinic sites. Secondary analyses will complement these primary objectives to provide a complete picture of the risks and benefits of each HAART regimen. Other secondary analysis will address whether HAART started in pregnancy leads to infant prematurity and low birth weight; whether LPV/RTV concentrations are low in pregnancy; and whether low drug concentrations in plasma and breast milk are associated with viral load and resistance mutations in these compartments, and with MTCT. The Botswana government currently offers HAART to all citizens with CD4 cell counts < 200 cells/mm3, and is considering offering TZV-based HAART to HIV-infected pregnant women with higher CD4 cell counts for PMTCT. The Botswana government has given explicit support for this protocol to occur in four existing Botswana-Harvard AIDS Institute Partnership (BHP) locations to help guide future policy decisions
Keywords: No Project Terms available
Project start date: 2005-09-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
5U01AI066454-06 (2010): $866664
5U01AI066454-03 (2007): $857739
5U01AI066454-02 (2006): $1003564
1U01AI066454-01A1 (2005): $341413
Roger L Shapiro
Harvard University (sch Of Public Hlth) Public Health Campus Boston, Ma 02115
Grant 5K23HD001330-05 from National Institute Of Child Health And Human Development IRG: CHHD
Abstract: Adapted from applicant s description) Roger L. Shapiro, M.D. is an infectious diseases fellow at the Massachusetts General Hospital/Brigham and Women s Hospital program in Boston, and has completed the two year Epidemic Intelligence Service training program at the Centers for Disease Control and Prevention (CDC). His work at CDC was with the Foodborne and Diarrheal Diseases Branch, and his research projects focused on international health issues; he established a diarrheal surveillance system in rural western Kenya, and performed case-control and cohort studies in Kenya and Argentina. His future career plans are to continue working on international epidemiology projects in the field of HIV, through the mentorship of Dr. Max Essex at the Harvard AIDS Institute. HIV-1 prevalence among women of child-bearing age in the southern region of Africa is approximately 25-40%, and more than a third of infants born to these women will become infected. Reliance on breastfeeding throughout Sub-Saharan Africa, and the high prevalence of a potentially more virulent strain of HIV-l (subtype C), make perinatal transmission studies performed in developing countries difficult to generalize to Africa. Unfortunately, areas with the highest HIV-l prevalence are also areas where I not breast-feeding has been associated with higher mortality among infants, largely from diarrheal disease. The protective effect of breast milk among infants born to HIV infected mothers is unknown. An intervention with an extended period of antiretroviral treatment given to infants born to HIV infected women, performed in Botswana where breast-feeding is almost universal and where HIV-1 subtype C predominates, could provide an opportunity to address the unanswered question of a protective role of antiretroviral drugs during breast-feeding in this region of Africa. The. planned intervention will consist of giving 1) all women ZDV + 3TC from 34 weeks of gestation to one week post-partum, 2) one group of infants ZDV+ 3TC for 1 week followed by formula feeding until 6 months of age, and 3) another group of infants ZDV+3TC for 1 week followed by ZDV and breast-feeding until 6 months of age. The primary objective of the study is to determine the potential efficacy of ZDV for reducing HIV-l subtype C transmission by breast- feeding. In addition to being a co-investigator on this intervention, Dr. Shapiro will be responsible for designing and implementing a diarrheal disease study among this cohort. He will evaluate diarrheal disease among infants through maternal questionnaire data and selected laboratory surveillance; this aspect of the study will be designed to assess the differences between formula and breastfeeding, to study the correlation between maternal viral load and diarrheal disease among the infants, and to determine if maternal HIV infection reduces the protective effect of breastmilk. Ultimately, these findings will further elucidate the risks and benefits of breast feeding among HIV-1 subtype C infected mothers. The study will be carried out in three towns in southeast Botswana as a collaborative effort between the Harvard AIDS Institute and the AIDS/STD Unit of Botswana at Gaborone (AIDSBG).
Keywords: AIDS education /prevention, AIDS therapy, HIV infection, breast feeding, diarrhea, human immunodeficiency virus 1, human therapy evaluation, lamivudine, vertical transmission, zidovudine, clinical trial, combination chemotherapy, passive immunization, pediatric AIDS, pediatric pharmacology, virus classification, Africa, clinical research, human pregnant subject, human subject, infant human (0-1 year)
Project start date: 2000-06-06
Project end date: 2006-05-31
5K23HD001330-05 (2004): $120338
5K23HD001330-04 (2003): $119852
5K23HD001330-02 (2001): $130167
1K23HD001330-01 (2000): $129303