Presenter : Dr T. G. Nematadzira on behalf of The IMPAACT PROMISE 1077BF/1077FF Team

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Efficacy and Safety of Two Strategies to Prevent
Perinatal HIV Transmission results from the
Antepartum Component of the PROMISE study

• Presenter Dr T. G. Nematadzira on behalf of
  The IMPAACT PROMISE 1077BF/1077FF Team

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IMPAACT PROMISE Sites
PROMISE is an ongoing prospective, open label
randomized trial being conducted at NIH IMPAACT
Clinical Research Sites in resource-limited
settings

• Sites in
• India(1)
• Malawi (2)
• South Africa (5)
• Tanzania (1)
• Uganda (1)
• Zambia (1)
• Zimbabwe (3)

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OBJECTIVES of the antepartum component

• To evaluate the comparative efficacy of
  maternal triple ARV prophylaxis versus antepartum
  ZDV sdNVP TRV tail to reduce antepartum and
  intrapartum HIV transmission.
• To assess and compare the safety and
  tolerability of triple ARVs compared to other
  proven regimens among healthy HIV women with
  higher CD4 counts.
• To assess HIV transmission rates at birth by
  study arm.

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PROMISE Methods

• Eligibility based on
• Currently pregnant, gestational age gt 14 weeks,
  documented HIV infection
• No receipt of triple ARVs in current pregnancy
• Did not meet country guidelines for ART
• CD4 gt 350 cells/uL or gt country-specific
  threshold for ART if it was above 350 cells/uL
• Laboratory
• Hematology and ALT screening values lt grade 3
• Cr Cl gt 60 mL/min (Cockroft-Gault equation)
• Age of legal majority
• No active TB or other serious health conditions
• No social circumstances that would prevent follow
  up

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PROMISE Methods

• Screening and recruitment were done after written
  informed consent was obtained which included
  discussion of current country PMTCT guidelines
  and the womans options.
• 3529 women were enrolled and seen at 2, 4, 8, 12
  weeks and then every 4 weeks till delivery.
• After delivery, women and infants were seen at
  week 1(between 6-12 days post delivery under V 2,
  and 5-14 days in V3)
• Laboratory safety testing was done at all these
  visits. CD4 was done at screening and entry
  labor/delivery and 1 week post partum visit
  viral load (VL) at entry, wk 4, L/D, and week 1

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Today Focus on Antepartum Component
Antepartum Labor/ Postpartum
Maternal Health (14 wks-term)
Delivery (for duration of BF)
(after BF cessation)

Maternal CD4 gt350
infant uninfected at birth
R a n d o m i z e
Triple ARV Prophylaxis
R a n d o m i z e
Infant NVP Prophylaxis
Late Presenters
ENROLLED 3,529 WOMEN
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Antepartum ComponentMaternal Randomization
Pregnant Women (both HBV and HBV-)
R
Arm A
Arm B
Arm C
ZDV
sdNVP

3TC
-
ZDV LPV
-
RTV
FTC
-
TDF LPV
-
RTV
FTC
-
TDF tail
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Maternal Baseline CharacteristicsYoung Pregnant
African Women with High CD4 Counts
Entry Characteristics (N3,523) Value
Age (median) 26 years
Race Black African 97
Gestational age (median) 26 weeks
CD4 cell count (median) 530 cells/uL
WHO Clinical Stage 1 97
Hepatitis B Surface Antigen 4
No ARV for prior PMTCT or no prior pregnancy 94
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Efficacy and Safety Outcomes Through 14 Days
Post-Delivery

• Mother to Child HIV Transmission (primary
  efficacy outcome)
• Maternal Adverse Events and Mortality
• Adverse Pregnancy Outcomes
• Infant Adverse Events and Mortality

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MTCT Through Age 14 Days Significantly Lower in
Triple ARV Arms
1.8
9 infections/ 1,710
25 infections/ 1,326
Difference in MTCT Risk (Repeated Confidence
Interval) -1.28 (95 CI -2.11, -0.44)
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Summary of safety results

• In HIV-infected pregnant women with high CD4, all
  regimens had low MTCT (lt2), but the triple ARVs
  had significantly lower early MTCT rates than ZDV
  Arm A regimen
• 0.5 (3TC-ZDVLPV-RTV) and 0.6 (FTC-
  TDFLPV/RTV) vs 1.8 (ZDV)
• There was an increased risk of maternal AEs with
  triple ARVs compared to ZDV regimen, driven by
  increased ALT.
• Higher risk of moderate but not severe pregnancy
  outcomes for triple ARVs compared to ZDV (such as
  LBW, preterm birth).
• There was a significantly lower risk of infant
  death for LPV-RTV ZDV/3TC vs TDF/FTC
• 0.6 (2/346) vs 4.4 (15/341), p0.001
• The difference was primarily seen in deaths among
  infants lt34 weeks gestation.

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Conclusions

• These results provide the first clinical trial
  evidence to support the current 2013 WHO
  recommendations for use of triple ARV regimens in
  pregnancy to achieve the lowest risk of
  transmission.
• The safety findings require further study.

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Acknowledgements
The PROMISE Team gratefully acknowledges the
dedication and commitment of the more than 3,500
mother-infant pairs without whom this study would
not have been possible.