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The Mma Bana Study

The Mma Bana Study. A Randomized Trial Comparing Highly Active Antiretroviral Therapy Regimens for Virologic Efficacy and the Prevention of Mother-to-Child HIV Transmission among Breastfeeding Women in Botswana.

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The Mma Bana Study

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  1. The Mma Bana Study A Randomized Trial Comparing Highly Active Antiretroviral Therapy Regimens for Virologic Efficacy and the Prevention of Mother-to-Child HIV Transmission among Breastfeeding Women in Botswana R. Shapiro, M. Hughes, A. Ogwu, D. Kitch, S. Lockman, C. Moffat, J. Makhema, S. Moyo, I. Thior, K. McIntosh, E. van Widenfelt, J. Leidner, K. Powis, A. Asmelash, E. Tumbare, S. Zwerski, U. Sharma, E. Handelsman, K. Mburu, O. Jayeoba, E. Moko, S. Souda, E. Lubega, M. Akhtar, C. Wester, W. Snowden, M. Martinez-Tristani, L. Mazhani, M. Essex, and The Mma Bana Study Team

  2. HAART for PMTCT • No randomized clinical trial has previously compared HAART regimens during pregnancy or breastfeeding • Little is known about the safety and efficacy of using maternal HAART to prevent MTCT during breastfeeding

  3. Study Background • At 4 clinical sites in southern Botswana, HIV-infected pregnant women were referred from government antenatal clinics, and 730 eligible women were enrolled in the study • Eligible women were stratified by CD4 count: • Women with CD4 counts > 200 cells/mm3 were randomized to either Trizivir or Kaletra/Combivir • Women with CD4 counts < 200 cells/mm3 were enrolled observationally, and received Nevirapine/Combivir according to Botswana government guidelines

  4. Study Design Intrapartum (supplemental AZT) Follow-up (2 years) Breastfeeding (6 months) (Rapid weaning before 6 mo visit) Antepartum (26-34 wks) 560 women with CD4 > 200 cells/mm3 randomized to: 170 women with CD4 < 200 cells/mm3 or AIDS enrolled observationally: Infants received single-dose NVP at birth and AZT x 1 month Arm A vs. Arm B Trizivir (Abacavir/AZT/3TC) Kaletra / Combivir (Lopinavair/ritonavir/AZT/3TC) Intrapartum (supplemental AZT) Follow-up (2 years) Breastfeeding (6 months) (Rapid weaning before 6 mo visit) Antepartum (18-34 wks) Obs Arm Nevirapine / Combivir (Nevirapine/AZT/3TC) HAART continued for treatment

  5. Primary Objectives • Maternal HIV-1 RNA suppression to < 400 copies/mL among randomized arms at: (a) Delivery (b) Throughout breastfeeding at 1, 3, and 6 months (or by weaning) 2) MTCT rate in overall study population

  6. Follow-up and Study Completeness • Loss to follow-up was low: • 95% of women and 97% of infants were followed to 6 months or death • Endpoint completeness was high: • Virologic: • 98% of women had a delivery HIV-1 RNA, 99.7% of breastfeeding women had >1 HIV-1 RNA during breastfeeding • MTCT: • 99.6% of infants had known birth PCR status (3 died before testing) • 95% of infants had known PCR status at 6 months or within 1 day of death

  7. Maternal Baseline Characteristics No differences by arm in education, income, electricity in home, baseline hemoglobin, or hepatitis B status. Median HAART duration prior to delivery = 11 weeks (randomized), 13 weeks (obs)

  8. Duration of Breastfeeding and HAART Adherence • Breastfeeding: • 97% of women initiated breastfeeding (all on HAART) • 93% exclusively breastfed through the time of weaning • 71% breastfed for > 5 months • < 1% breastfed beyond the 6 month visit • HAART Adherence (similar by HAART regimen): • 6% missed 3 or more total days of HAART

  9. Primary Virologic Endpoints: HIV-1 RNA Suppression to < 400 copies/mL at Delivery and During Breastfeeding * Suppression during breastfeeding defined as at least one available viral load while breastfeeding, and no result > 400 copies/mL 95% CI for difference between Arm A vs. B at delivery = (-2%, 10%) 95% CI for difference between Arm A vs. B during breastfeeding = (-8%, 6%)

  10. Maternal HIV RNA Suppression to < 400 copies/mL % Delivery 1 Months 3 Months 6 Months During breastfeeding N: 709 661 633 501 669 Arm A (TZV) Arm B (Kal/CBV) Obs Arm (NVP/CBV)

  11. Primary MTCT Endpoint • 1% overall transmission through 6 months • 95% CI for overall MTCT rate = (0.5%, 2.0%) • P-value for difference in proportions for Arm A vs. B = 0.53 • *Results exclude one unconfirmed + birth PCR followed by death in Arm A • Including this infant as a + PCR: P-value for difference in proportions for Arm A vs. B = 0.42

  12. Characteristics of Transmitting Women In utero transmissions * Unconfirmed infection: positive PCR followed by infant death ** maternal death at delivery Breastfeeding transmissions

  13. Characteristics of Transmitting Women In utero transmissions * Unconfirmed infection: positive PCR followed by infant death ** maternal death at delivery Breastfeeding transmissions

  14. Characteristics of Transmitting Women In utero transmissions * Unconfirmed infection: positive PCR followed by infant death ** maternal death at delivery Breastfeeding transmissions

  15. Characteristics of Transmitting Women In utero transmissions * Unconfirmed infection: positive PCR followed by infant death ** maternal death at delivery Breastfeeding transmissions

  16. Characteristics of Transmitting Women In utero transmissions * Unconfirmed infection: positive PCR followed by infant death ** maternal death at delivery Breastfeeding transmissions

  17. Stillbirths, Prematurity, Low Birth Weight, and Congenital Abnormalities * Gestational age determined by last menstrual period and/or ultrasound

  18. Maternal Deaths and Adverse Events More grade 3 and 4 adverse events in the observational arm (CD4 < 200)

  19. Infant Deaths and Adverse Events Grade 3 and 4 adverse events similar for all infants, including those born to women with more advanced HIV in the observational arm Mortality > 6 months NOT included in these results

  20. Summary • HIV-1 RNA suppression to < 400 copies/mL was similar at delivery and throughout breastfeeding by randomized arm, and for the observational arm • 95% suppressed at delivery, 93% throughout breastfeeding • Among 709 live births, HIV transmission was only 1% overall, and only 2 transmissions occurred during breastfeeding (0.3%) • Lowest MTCT rate reported in a breastfeeding population • HAART regimens were safe and well-tolerated for women and for their breastfeeding infants

  21. Conclusion • Maternal HAART from early in the third trimester of pregnancy through 6 months of breastfeeding is a safe and very effective strategy for preventing MTCT while allowing for the benefits of breastfeeding

  22. Acknowledgements Support for this study was provided by NIAID (U01-AI066454) Medications provided by: the Botswana Government, Glaxo Smith Kline, and Abbott We also want to thank: Botswana Ministry of Health: Dr. Khumo Sepoine, Mrs. Shenaaz El Halabi, Mr Pilate Khulumani, Mrs Mary Kasule, Dr. Howard Moffat, Dr. Haruna Baba Jubril, Dr Balosang, PMTCT unit Princess Marina Hospital, Gaborone Staff of Maternity, Post natal & Children’s ward  Scottish Livingstone Hospital, Molepolole Staff of Maternity, Post natal & Children’s ward Deborah Retief Memorial Hospital, Mochudi Staff of Maternity, Post natal & Children’s ward Athlone Hospital Lobatse Staff of Maternity, Post natal & Children’s ward District Health Teams (Molepolole & Mochudi). City Council Clinics team (Lobatse & Gaborone) GSK: Edde Loeliger Baylor: Prof Gabriel Anabwani, Dr Elizabeth Lowenthal Brigham and Women’s Hospital: Ruth Tuomola Beth Israel Deaconess Medical Ctr: Linda Shipton Harvard Medical School: Jennifer Chen Oxford University: Philip Goulder, Philippa Mathews NIH: Lynne Mofenson DSMB Members The Mma Bana Study Participants BHP and HSPH Staff: Lillian Makori, Gloria Mayondi, Agnes Modise, Venice Modikwa, Ria Madison, Tlhongbotho Masoloko, Daisy Ramalekane, Molly Pretorius Holme, Heather Carey, Sara Mazzola, Carrie Kachoria, Raabya Rossenkahn, Vlad Novitsky, Chris Rowley, Michael Roy, Lendsey Melton, Chikezie Nwankwo, Scott Dryden Peterson, Onalenna Nthase, Norah Mawoko, Elias Woldegabriel, Kasonde Micheal, Chandan Harikrishnan, Jane Magetse, Joyce Lubinda, Tebogo Kakhu, Thena Tumediso, Modiegi Diseko, Mosetsanagape Galekhutle, Keamogetse Rebatenne, Mavis Moeng, Kebaibphe Ntalabgwe, Ditlamelo Mareme, Victoria Kgwadi, Kaone Kgati, Keitumetse Sakana, Best Mafoko, Lazarus Moremi, Jimmy Nkgau, Ilori Adewale, Banno Janet Moorad, Dipotso Arbi, Thena Tumediso, Kesego Dudu Kooreng, Selebaleng Vinoliah Simon, Maggie Mosetsanagape Nkgau, Collen Rananna, Rejoice Molefe, Nametso Dimpho Lekwape, Tebogo Ncube, Eldah Kakanyo Tshotlego, Segomotso Mapote, Radinku Tshegofatso, Emmanuel Keikotlhae, William Keboutlwe, Hanqiwe Olebeng, Seleetso Ndicky Modibedi, Tshepo Silwane, Tshepiso Patricia Morupisis, Ntsholeng Kekgethile, Sydney Kgwefane, Julius Kgangetsile, Nnahurumnanya Iwe, Modiegi Diseko, Tseo Khudube, Malebogo Ntshimane, Hanqiwe Olebeng, Maureen Gower, Nthabiseng Kgaodi, Kate Selathwe, Lorraine Phiri, Rosemary Musonda, Phillimon Segopodi , Dorcas Moses, Bonolo Khumotaka , Phibeon Munyanadzi Mangwendeza, Gertrude Ditshotlo, Alex Ntau, Poko Molwan

  23. Thank you!

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