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| ID | Type | Description | Link |
|---|---|---|---|
| U01AI064002 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Harvard School of Public Health (HSPH) | OTHER |
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Anti-HIV drug regimens have dramatically improved the rates of prevention of mother-to-child transmission (MTCT) of HIV in developed countries. However, little is known of the effectiveness of such regimens in developing countries, such as Botswana. This study will determine whether Trizivir (TZV), a single pill containing abacavir sulfate, lamivudine, and zidovudine (ABC/3TC/ZDV), or lopinavir/ritonavir (LPV/r) and lamivudine/zidovudine (3TC/ZDV) is more effective in reducing HIV-1 viral load and preventing MTCT among HIV infected pregnant women in Botswana.
While perinatal HIV infection has become rare in developed countries through the use of highly active antiretroviral therapy (HAART), it remains a serious problem in developing countries. Botswana has a population of approximately 1.7 million; the prevalence of HIV in Botswana is about 37.4%. In the developed world, HAART has revolutionized the prevention of MTCT among nonbreastfed infants. This trial will compare the effectiveness of a protease inhibitor (PI)-based regimen versus a triple nucleoside reverse transcriptase inhibitor (NRTI)-based regimen in preventing MTCT of HIV.
This study will last up to 24 months for mothers and their children. Participants will be stratified based on their CD4 count at screening. Women with CD4 counts of 200 cells/mm3 or more will be in one of two treatment groups and will be randomly assigned to receive either TZV twice daily or LPV/RTV and 3TC/ZDV twice daily. Once in labor, treatment group participants will continue to take their assigned HAART regimen and will also be given additional ZDV. Women with CD4 counts less than 200 cells/mm3 will receive nevirapine (NVP) once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group.
Shortly after birth, infants will receive single-dose NVP. A 1-month supply of ZDV will be provided to the mother to administer daily to her child. Mothers will stop HAART at 6 months postpartum or when they stop breastfeeding, whichever occurs earlier. A clinical evaluation, blood collection, and HIV prevention counseling will occur at all maternal visits. An obstetrical exam and physical exam will occur at selected visits. Women will provide at least four samples of breast milk during the first 5 months postpartum. For infants, a clinical evaluation will occur at every visit, and a physical exam and blood collection will occur at selected visits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trizivir (TZV) Arm | Experimental | Participants in the TZV Arm (Arm 1A) will be pregnant women who have CD4 counts of 200 cells/mm3 or more. As the intervention, they will receive TZV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. |
|
| Kaletra Arm | Experimental | Participants in the Kaletra Arm (Arm 1B) will be pregnant women who have CD4 counts of 200 cells/mm3 or more. As the intervention, they will receive Lamivudine/Zidovudine (3TC/ZDV) and Lopinavir/Ritonavir (LPV/RTV) twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. |
|
| Nevirapine (NVP) Arm | Experimental | Participants in the NVP Arm (Arm 2) will be pregnant women who have have CD4 counts less than 200 cells/mm3. These participants will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trizivir | Drug | 300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Virologic Suppression | Suppression of the plasma HIV-1 RNA level to less than 400 copies per milliliter | Throughout study, including breastfeeding, assessed up to 24 months |
| Number of HIV+ Infants | Number of infants with HIV-positive status | Throughout study, including breastfeeding, assessed up to 24 months |
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Inclusion Criteria for Mothers:
Exclusion Criteria for Mothers:
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| Name | Affiliation | Role |
|---|---|---|
| Roger Shapiro, MD, MPH | Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Botswana-Harvard School of Public Health Partnership for Research and Education | Principal Investigator |
| Claire Moffat, MD, MPH | Department of Immunology and Infectious Diseases, Harvard School of Public Health, Botswana-Harvard School of Public Health Partnership for Research and Education | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Princess Marina Hosp., BHP Study Clinic, Gaborone Shapiro CRS | Gaborone | Botswana | ||||
| Athlone Hosp., BHP Study Clinic, Lobatse Shapiro CRS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11981365 | Background | Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, Hayani K, Handelsman E, Smeriglio V, Hoff R, Blattner W; Women and Infants' Transmission Study Group. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):484-94. doi: 10.1097/00126334-200204150-00009. | |
| 12095383 | Background | Dorenbaum A, Cunningham CK, Gelber RD, Culnane M, Mofenson L, Britto P, Rekacewicz C, Newell ML, Delfraissy JF, Cunningham-Schrader B, Mirochnick M, Sullivan JL; International PACTG 316 Team. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA. 2002 Jul 10;288(2):189-98. doi: 10.1001/jama.288.2.189. |
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| ID | Title | Description |
|---|---|---|
| FG000 | TZV Arm | Participants in Arm 1A will have CD4 counts of 200 cells/mm3 or more and will receive TZV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. Trizivir: 300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily |
| FG001 | Kaletra Arm | Participants in Arm 1B will have CD4 counts of 200 cells/mm3 or more and will receive LPV/RTV and 3TC/ZDV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. Lamivudine/Zidovudine: 150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily Lopinavir/Ritonavir: 400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily |
| FG002 | NVP Arm | Participants in Arm 2 will have CD4 counts less than 200 cells/mm3 and will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group. Nevirapine: 200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | TZV Arm | Participants in Arm 1A will have CD4 counts of 200 cells/mm3 or more and will receive TZV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. Trizivir: 300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Virologic Suppression | Suppression of the plasma HIV-1 RNA level to less than 400 copies per milliliter | Posted | Count of Participants | Participants | Throughout study, including breastfeeding, assessed up to 24 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TZV Arm | Participants in Arm 1A will have CD4 counts of 200 cells/mm3 or more and will receive TZV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. Trizivir: 300 mg abacavir sulfate/150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 3 or 4 Laboratory Event | Blood and lymphatic system disorders | Systematic Assessment | Neutropenia or anemia or liver function test (LFT) abnormality |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Roger Shapiro | Harvard TH Chan School of Public Health | 617-432-2334 | rshapiro@hsph.harvard.edu |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C418262 | abacavir, lamivudine, and zidovudine drug combination |
| C109078 | lamivudine, zidovudine drug combination |
| D061466 | Lopinavir |
| D019829 | Nevirapine |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Lamivudine/Zidovudine | Drug | 150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily |
|
|
| Lopinavir/Ritonavir | Drug | 400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily |
|
|
| Nevirapine | Drug | 200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily |
|
|
| Lobatse |
| Botswana |
| Deborah Reteif Hosp., BHP Study Clinic, Mochudi Shapiro CRS | Mochudi | Botswana |
| Scottish Livingstone Hosp., BHP Study Clinic, Molepolole Shapiro CRS | Molepolole | Botswana |
| 16369449 | Background | Jones BM, Chiu SS, Wong WH, Lim WW, Lau YL. Cytokine profiles in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy. MedGenMed. 2005 May 3;7(2):71. |
| 12599045 | Background | Moodley D, Moodley J, Coovadia H, Gray G, McIntyre J, Hofmyer J, Nikodem C, Hall D, Gigliotti M, Robinson P, Boshoff L, Sullivan JL; South African Intrapartum Nevirapine Trial (SAINT) Investigators. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis. 2003 Mar 1;187(5):725-35. doi: 10.1086/367898. Epub 2003 Feb 24. |
| 12599046 | Background | Richardson BA, John-Stewart GC, Hughes JP, Nduati R, Mbori-Ngacha D, Overbaugh J, Kreiss JK. Breast-milk infectivity in human immunodeficiency virus type 1-infected mothers. J Infect Dis. 2003 Mar 1;187(5):736-40. doi: 10.1086/374272. Epub 2003 Feb 12. |
| 12599047 | Background | Rousseau CM, Nduati RW, Richardson BA, Steele MS, John-Stewart GC, Mbori-Ngacha DA, Kreiss JK, Overbaugh J. Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis. 2003 Mar 1;187(5):741-7. doi: 10.1086/374273. Epub 2003 Feb 18. |
| 26684818 | Derived | Powis KM, Smeaton L, Hughes MD, Tumbare EA, Souda S, Jao J, Wirth KE, Makhema J, Lockman S, Fawzi W, Essex M, Shapiro RL. In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana. AIDS. 2016 Jan;30(2):211-20. doi: 10.1097/QAD.0000000000000895. |
| 25037041 | Derived | Powis K, Lockman S, Smeaton L, Hughes MD, Fawzi W, Ogwu A, Moyo S, van Widenfelt E, von Oettingen J, Makhema J, Essex M, Shapiro RL. Vitamin D insufficiency in HIV-infected pregnant women receiving antiretroviral therapy is not associated with morbidity, mortality or growth impairment in their uninfected infants in Botswana. Pediatr Infect Dis J. 2014 Nov;33(11):1141-7. doi: 10.1097/INF.0000000000000428. |
| 24180000 | Derived | Shapiro RL, Kitch D, Ogwu A, Hughes MD, Lockman S, Powis K, Souda S, Moffat C, Moyo S, McIntosh K, van Widenfelt E, Zwerski S, Mazhani L, Makhema J, Essex M. HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana. AIDS. 2013 Jul 31;27(12):1911-20. doi: 10.1097/qad.0b013e32836158b0. |
| 24086319 | Derived | Dryden-Peterson S, Jayeoba O, Hughes MD, Jibril H, McIntosh K, Modise TA, Asmelash A, Powis KM, Essex M, Shapiro RL, Lockman S. Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in HAART-exposed, HIV-uninfected infants. PLoS One. 2013 Sep 23;8(9):e74171. doi: 10.1371/journal.pone.0074171. eCollection 2013. |
| 21266910 | Derived | Dryden-Peterson S, Shapiro RL, Hughes MD, Powis K, Ogwu A, Moffat C, Moyo S, Makhema J, Essex M, Lockman S. Increased risk of severe infant anemia after exposure to maternal HAART, Botswana. J Acquir Immune Defic Syndr. 2011 Apr 15;56(5):428-36. doi: 10.1097/QAI.0b013e31820bd2b6. |
| 21124227 | Derived | Powis KM, Smeaton L, Ogwu A, Lockman S, Dryden-Peterson S, van Widenfelt E, Leidner J, Makhema J, Essex M, Shapiro RL. Effects of in utero antiretroviral exposure on longitudinal growth of HIV-exposed uninfected infants in Botswana. J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):131-8. doi: 10.1097/QAI.0b013e3181ffa4f5. |
| 20554983 | Derived | Shapiro RL, Hughes MD, Ogwu A, Kitch D, Lockman S, Moffat C, Makhema J, Moyo S, Thior I, McIntosh K, van Widenfelt E, Leidner J, Powis K, Asmelash A, Tumbare E, Zwerski S, Sharma U, Handelsman E, Mburu K, Jayeoba O, Moko E, Souda S, Lubega E, Akhtar M, Wester C, Tuomola R, Snowden W, Martinez-Tristani M, Mazhani L, Essex M. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med. 2010 Jun 17;362(24):2282-94. doi: 10.1056/NEJMoa0907736. |
| Kaletra Arm |
Participants in Arm 1B will have CD4 counts of 200 cells/mm3 or more and will receive LPV/RTV and 3TC/ZDV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. Lamivudine/Zidovudine: 150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily Lopinavir/Ritonavir: 400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily |
| BG002 | NVP Arm | Participants in Arm 2 will have CD4 counts less than 200 cells/mm3 and will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group. Nevirapine: 200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | NVP Arm | Participants in Arm 2 will have CD4 counts less than 200 cells/mm3 and will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group. Nevirapine: 200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily |
|
|
| Primary | Number of HIV+ Infants | Number of infants with HIV-positive status | Analysis is based on actual number of available patients, and may not perfectly match the Patient Flow module. | Posted | Number | Infants | Throughout study, including breastfeeding, assessed up to 24 months |
|
|
|
| 1 |
| 285 |
| 42 |
| 285 |
| 0 |
| 285 |
| EG001 | Kaletra Arm | Participants in Arm 1B will have CD4 counts of 200 cells/mm3 or more and will receive LPV/RTV and 3TC/ZDV twice daily. Once in labor, these participants will continue to take TZV twice daily and will also be given additional ZDV. Lamivudine/Zidovudine: 150 mg lamivudine/300 mg zidovudine tablet taken orally twice daily Lopinavir/Ritonavir: 400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily | 0 | 275 | 32 | 275 | 0 | 275 |
| EG002 | NVP Arm | Participants in Arm 2 will have CD4 counts less than 200 cells/mm3 and will receive NVP once daily for the first 14 days, then twice daily, and 3TC/ZDV twice daily; these women will be in the observational group. Nevirapine: 200 mg tablet taken orally daily for the first 14 days before receiving 200 mg tablet taken orally twice daily | 3 | 170 | 48 | 170 | 0 | 170 |
|
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| 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 |
| D011725 |
| Pyridines |