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| ID | Type | Description | Link |
|---|---|---|---|
| R01HD061265 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Harvard Medical School (HMS and HSDM) | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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The purpose of this study is to find ways to improve infant health and survival among infants whose mothers are HIV-infected but who do not themselves have HIV.
As improved MTCT prevention interventions reduce the number of HIV-infected infants in the antepartum and peripartum periods, interventions to improve HIV-free survival among HIV-uninfected infants are needed. Morbidity and mortality are increased among HIV-uninfected infants born to HIV-infected mothers, and reduced infant survival among HIV-exposed infants may lead to as many deaths as HIV infection itself. In Botswana, the use of formula feeding or shorter breastfeeding may worsen the problem of early infant mortality among HIV-exposed infants.
The study will enroll pregnant or postpartum HIV-1-infected women, and their HIV-uninfected infants in Botswana. At 2-4 weeks of age, live HIV-uninfected infants will be randomized to receive either double-blinded cotrimoxazole (CTX) or placebo from 2-4 weeks through 15 months. In addition, breastfeeding (BF) infants will be randomized to BF until either 6 or 12 months of age. Children will be followed prospectively until 18 months of age. The primary endpoint will be survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of BF among those BF at randomization. Secondary endpoints will evaluate survival and morbidity/mortality at 12 and 15 months; HIV-free survival to 18 months; and the safety of CTX prophylaxis. Secondary observational objectives include comparing MTCT and mortality by initial feeding method (formula feeding or any BF > 1 month), and an analysis of maternal characteristics as predictors for initial feeding choice and HIV-free survival. All women and infants will receive standard antenatal and peripartum prophylaxis from the Botswana government for MTCT prevention (PMTCT), and will choose a feeding method with counseling. Breastfeeding infants will receive infant nevirapine (NVP) prophylaxis or will be protected from MTCT by the use of maternal HAART.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| infant cotrimoxazole | Active Comparator |
| |
| infant placebo | Placebo Comparator |
| |
| exclusive breastfeeding for 6 months | Active Comparator |
| |
| exclusive breastfeeding for 12 months | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cotrimoxazole prophylaxis | Drug | 100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Survival | The primary outcome measure is survival at 18 months comparing all infants in the CTX vs. placebo arms, and by randomized duration of breastfeeding among those breastfeeding at randomization. | 18 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| HIV-free Survival | Secondary outcome measures will evaluate HIV-free survival between 4 weeks and 18 months among infants randomized to either 6 months or 12 months of breastfeeding. | 18 months of age |
| Safety of CTX prophylaxis |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shahin Lockman, MD, MS | Harvard School of Public Health (HSPH) | Principal Investigator |
| Roger L Shapiro, MD, MPH | Harvard School of Public Health (HSPH) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Princess Marina Hospital | Gaborone | Botswana | ||||
| Athlone Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29119726 | Derived | Powis KM, Souda S, Lockman S, Ajibola G, Bennett K, Leidner J, Hughes MD, Moyo S, van Widenfelt E, Jibril HB, Makhema J, Essex M, Shapiro RL. Cotrimoxazole prophylaxis was associated with enteric commensal bacterial resistance among HIV-exposed infants in a randomized controlled trial, Botswana. J Int AIDS Soc. 2017 Nov;20(3):e25021. doi: 10.1002/jia2.25021. | |
| 28395844 | Derived | Lockman S, Hughes M, Powis K, Ajibola G, Bennett K, Moyo S, van Widenfelt E, Leidner J, McIntosh K, Mazhani L, Makhema J, Essex M, Shapiro R. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): a double-blind, randomised, placebo-controlled trial. Lancet Glob Health. 2017 May;5(5):e491-e500. doi: 10.1016/S2214-109X(17)30143-2. |
| Label | URL |
|---|---|
| Shapiro RL et al. Similar mortality with cotrimoxazole vs. placebo in HIV-exposed uninfected children, Conference on Retroviruses and Opportunistic Infections (CROI 2016), Boston, abstract 37. | View source |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | May 22, 2013 | Jun 7, 2019 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D009503 | Neutropenia |
| D000740 | Anemia |
| D001942 | Breast Feeding |
| D066088 | Infant Death |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D015662 | Trimethoprim, Sulfamethoxazole Drug Combination |
| D000375 | Aging |
| D007774 | Lactation |
| ID | Term |
|---|---|
| D013420 | Sulfamethoxazole |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
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|
| cotrimoxazole placebo | Drug | 100mg/20mg per day (or 2.5 mL of syrup from a 200mg/40mg per 5mL suspension) from 1-6 months, followed by 200mg/40mg per day (or 5 mL of syrup from a 200mg/40mg per 5 mL suspension) from 6 to 12 months |
|
| exclusive breastfeeding until 6 months of age | Behavioral | Breastfeeding for 6 months, followed by formula feeding for 6 month. Breastfeeding infants will be prophylaxed with maternal highly active antiretroviral therapy (HAART) (if available) or with infant nevirapine. |
|
| breastfeeding for 12 months | Behavioral | Breastfeeding infants will be prophylaxed with maternal HAART (if available) or with infant nevirapine. |
|
Secondary outcome measures will evaluate the safety of CTX prophylaxis through 18 months
| 18 months |
| Morbidity and mortality | Secondary outcome measures will evaluate morbidity and mortality to 18 months. | 18 months of age |
| Lobatse |
| Botswana |
| Scottish Livingstone Hospital | Molepolole | Botswana |
| 28339500 | Derived | Ajibola G, Zash R, Shapiro RL, Batlang O, Botebele K, Bennett K, Chilisa F, Widenfelt EV, Makhema J, Lockman S, Holmes LB, Powis KM. Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana. PLoS One. 2017 Mar 24;12(3):e0173800. doi: 10.1371/journal.pone.0173800. eCollection 2017. |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D000380 | Agranulocytosis |
| D007970 | Leukopenia |
| D000095542 | Cytopenia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007960 | Leukocyte Disorders |
| D005247 | Feeding Behavior |
| D001519 | Behavior |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064419 | Chemically-Induced Disorders |
| D009930 |
| Organic Chemicals |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D014295 | Trimethoprim |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D048788 | Growth and Development |
| D010829 | Physiological Phenomena |
| D055703 | Reproductive Physiological Phenomena |
| D012101 | Reproductive and Urinary Physiological Phenomena |
| D049590 | Postpartum Period |