The Mma Bana Study

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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
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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

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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 gt 200 cells/mm3 were
  randomized to either Trizivir or Kaletra/Combivir
• Women with CD4 counts lt 200 cells/mm3 were
  enrolled observationally, and received
  Nevirapine/Combivir according to Botswana
  government guidelines

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Study Design

• 560 women with CD4 gt 200 cells/mm3 randomized to
• 170 women with CD4 lt 200 cells/mm3 or AIDS
  enrolled observationally
• Infants received single-dose NVP at birth and AZT
  x 1 month
  

Intrapartum (supplemental AZT)
Follow-up (2 years)
Antepartum (26-34 wks)
Breastfeeding (6 months) (Rapid weaning before 6
mo visit)
Arm A vs. Arm B
Trizivir (Abacavir/AZT/3TC)

Kaletra / Combivir (Lopinavair/ritonavir/AZT/3TC)


Intrapartum (supplemental AZT)
Breastfeeding (6 months) (Rapid weaning before 6
mo visit)
Follow-up (2 years)
Antepartum (18-34 wks)
Obs Arm
Nevirapine / Combivir (Nevirapine/AZT/3TC)
HAART continued for treatment
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Primary Objectives

• Maternal HIV-1 RNA suppression to lt 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

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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 gt1 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

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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)
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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 gt 5 months
• lt 1 breastfed beyond the 6 month visit
• HAART Adherence (similar by HAART regimen)
• 6 missed 3 or more total days of HAART

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Primary Virologic Endpoints HIV-1 RNA
Suppression to lt 400 copies/mL at Delivery and
During Breastfeeding
Suppression during breastfeeding defined as at
least one available viral load while
breastfeeding, and no result gt 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)
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Maternal HIV RNA Suppression to lt 400 copies/mL

Delivery 1 Months
3 Months 6 Months
During breastfeeding N 709
661 633 501
669
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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

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Characteristics of Transmitting Women
In utero transmissions
Unconfirmed infection positive PCR followed by
infant death maternal death at delivery
Breastfeeding transmissions
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Characteristics of Transmitting Women
In utero transmissions
Unconfirmed infection positive PCR followed by
infant death maternal death at delivery
Breastfeeding transmissions
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Characteristics of Transmitting Women
In utero transmissions
Unconfirmed infection positive PCR followed by
infant death maternal death at delivery
Breastfeeding transmissions
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Characteristics of Transmitting Women
In utero transmissions
Unconfirmed infection positive PCR followed by
infant death maternal death at delivery
Breastfeeding transmissions
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Characteristics of Transmitting Women
In utero transmissions
Unconfirmed infection positive PCR followed by
infant death maternal death at delivery
Breastfeeding transmissions
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Stillbirths, Prematurity, Low Birth Weight, and
Congenital Abnormalities
Gestational age determined by last menstrual
period and/or ultrasound
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Maternal Deaths and Adverse Events
More grade 3 and 4 adverse events in the
observational arm (CD4 lt 200)
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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
gt 6 months NOT included in these results
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Summary

• HIV-1 RNA suppression to lt 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

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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

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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
Childrens ward  Scottish Livingstone Hospital,
Molepolole Staff of Maternity, Post natal
Childrens ward Deborah Retief Memorial Hospital,
Mochudi Staff of Maternity, Post natal
Childrens ward Athlone Hospital Lobatse Staff of
Maternity, Post natal Childrens ward District
Health Teams (Molepolole Mochudi). City Council
Clinics team (Lobatse Gaborone) GSK Edde
Loeliger Baylor Prof Gabriel Anabwani, Dr
Elizabeth Lowenthal Brigham and Womens 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

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Thank you!