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

Efficacy and Safety of Two Strategies to Prevent Perinatal HIV Transmission :

results from the Antepartum Component of the PROMISE study

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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 > 14 weeks, documented HIV infection

– No receipt of triple ARVs in current pregnancy– Did not meet country guidelines for ART– CD4 > 350 cells/uL or > country-specific threshold for

ART if it was above 350 cells/uL– Laboratory:

• Hematology and ALT screening values < grade 3• Cr Cl > 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

woman’s 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 15

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

Infant NVP Prophylaxis

Triple ARVProphylaxis

Randomize

Late Presenters

Continue Triple ARV Regimen

Stop All ARVs

Mother

Randomize

infant uninfected at birth

ZDVZDV +

sdNVP+TRV

Randomize

Maternal CD4 >350

Today: Focus on Antepartum Component

ENROLLED 3,529 WOMEN 6

Antepartum ComponentMaternal Randomization

Pregnant Women(both HBV+ and HBV-)

Arm A

ZDV + sdNVP + FTC-TDF tail

R

Arm B

3TC-ZDV + LPV-RTV

Arm C

FTC-TDF + LPV-RTV

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Maternal Baseline Characteristics:Young Pregnant African Women with High CD4 Counts

Entry Characteristics (N=3,523) 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%

Difference in MTCT Risk (Repeated Confidence Interval):

-1.28% (95% CI -2.11%, -0.44%) 10

25 infections/1,326

9 infections/1,710

Summary of safety results In HIV-infected pregnant women with high CD4, all regimens had

low MTCT (<2%), but the triple ARVs had significantly lower early MTCT rates than ZDV Arm A regimen:

– 0.5% (3TC-ZDV+LPV-RTV) and 0.6% (FTC- TDF+LPV/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), p=0.001 The difference was primarily seen in deaths among infants <34

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

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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.