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PMTCT Research
Didier Koumavi EKOUEVI
INSERM U-897, Bordeaux, France, Programme PACCI, site ANRS, Abidjan, Côte d’Ivoire
FMMP, Université de Lomé
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Mother-to-child transmission(MTCT) of HIV
• Without ARV interventions, MTCT rate is 15-40%
• Differences between populations are associated with maternal characteristics (HIV RNA viral load, CD4, clinical disease progression) and infant feeding
Infected children
Mother-to-child
transmission
HIV infection in women
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Objectives of PMTCT research
• To increase the efficacy of the ARV regimens during labor and breastfeeding period
• To increase PMTCT coverage
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Balancing act
Benefit ofMaternal Treatment
Risk ofAdverse Fetal Effects
Has direct benefit to maternal health plus prevention of MTCTThis outweighs any potential risks to fetus
Efficacy of antiretroviral drugs regimens
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1991-1993 : ACTG076/ANRS 024 trial
• First clinical trials of antiretroviral (ARV) drug prophylaxis for women and infants were conducted in Europe and the United States of America– 477 HIV-infected women – Treatment : Zidovudine >=14 weeks of gestation
• Results: rate of HIV transmission – Zidovudine arm : 8.3%– Placebo arm : 25.5% Reduction of 68%
Connor, New Engl J Med 19945
Three generations of PMTCT research in Sub-Saharan Africa
1st generation 1994-2002
Short-course ARV > 32 weeks
Replacement feeding or breastfeeding
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First generation (1994-2002): Short-course ARV regimen
0
5
10
15
20
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Rate of HIV transmission < 5% 7
Three generations of PMTCT research in Sub-Saharan Africa
1st generation1994-2002
Short-course ARV>32-26 weeks
gestation
Replacement feeding or breastfeeding
2nd generation2002-2014
Short-course ARV / HAART*
>28 weeks gestationBreastfeeding
+ARV prophylaxis
8* Eligibility criteria for HAART
Second generation (2003-2012) : Rate of HIV transmission < 2%
• HAART for the breastfeeding women– Mma Bana– MTCT-Plus – AMATA – KISUMU
• PEP for the breastfed infant– PEPI trial – SWEN– Promise-ANRS
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10
ARV Prophylaxis: Postnatal HIV Transmission Between Age 4-6 Weeks and 6-7 Months
0,9%0,6%
1,1%0,6%
1,2%0,8%
4,4% 4,4%
2,3%
0%
2%
4%
6%
8%
10%
% M
TCT
6 M
onth
s
MitraPlus
Amata KIBS DREAM Mitrainfant(3TC)
SIMBA(NVP)
Mashi(AZT)
SWEN(NVP)
PEPI-Malawi(NVP)
Maternal Postpartum HAART Infant Postpartum ARV
All also antepartum maternalARVs (Mashi only AZT)
No antepartum maternal ARV
Mom AZT/3TC
Mom AZT/ddI
Mom AZT
PMTCT research with ANRS
PROMISE-PEP study (ANRS 12174)1
Aim : efficacy of a treatment strategy to PMTCT of HIV-1 during 12 months of breastfeeding
Regimens : Lopinavir/Ritonavir vs. Lamivudine from day 7 until 4 weeks after cessation of to prevent postnatal HIV-1 acquisition (7 days and 50 weeks)
Next steps : comparative data on efficacy and tolerance of the two regimens will be available in September 2013
Transmission rate of MTCT
1.1% at 12 months
1. Towards Elimination of Breastfeeding Transmission by Infant Prep: Results of ANRS 12174 Trial Using Boosted Lopinavir or Lamivudine in Africa ; Thorkild Tylleskar, CROI 2013
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Current WHO PMTCT recommended interventions
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Eligible women
Non-eligiblewomen
Published in 2010 and updated in 2012 12
Towards the 2013 WHO*
• All HIV+ pregnant and breastfeeding women should initiate triple ARVs as soon as possible (Option B+)
• All women not eligible for antiretroviral therapy for their own health, consideration can be given to discontinue the antiretroviral regimen after the period of MTCT risk has ceased (option B)
New Guidelines on PMTCT will release mid 201313
2013 WHO recommendations*
• Treatment eligibility criteria: – CD4 <500 cells/ml ??– CD4 <350 cells (current recommendation)
• Preferred regimen (adults & PMTCT):TDF / (3TC or FTC) / EFV
7New Guidelines on PMTCT will release mid 201314
Paradox of the PMTCT research
• The new WHO program update recommends use of tenofovir/lamivudine/efavirenz is not “formally evaluated” among pregnant women
– Tenofovir + Emtricitabine : resistance study1,2
– Efavirenz : Amata study (Rwanda)3
1 TeMAA team AIDS 2009 & TEmAA, ANRS team, AIDS 2010, 2. CHI, B Lancet 20073. Peltier CA, AIDS 2009 15
Three generations of PMTCT research in Sub-Saharan Africa
1st generation1994-2002
Short-course ARV
> 32 weeks$
Replacement feeding or
breastfeeding
2nd generation2002-2014
Short-courseARV / HAART>28 weeks$
Breastfeeding+
ARV prophylaxis
3rd generation2012-2020
HAART> 14 weeks$
Breastfeeding
16$ Weeks of gestation
Research related to option B/B+ : Acceptability
• To evaluate the acceptability of and adherence to triple ARV regimens for PMTCT in women not yet candidates for ART
• To evaluate the effectiveness of Option B/B+ on MTCT rates
• To evaluate the costs and cost-benefit of Option B/B+
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Research related to optionB/B+ Pharmacovigilance
• Need of more pregnancy outcome and later infant outcome data
• Urgent to implement pharmacovigilancesystem – Pregnancy outcomes: preterm birth1, low birth
weight 2 , stillbirth, congenital anomalies– Safety of long-term HAART exposure among
infants: growth, bone mineral density, neurodevelopment
181. Powis KM, J Infect Dis. 2011, 2. Ekouevi, AIDS 2008
Is there any place for new antiretroviral drugs?
• Identify drugs that can be used safely among pregnant women– Physicians should be comfortable to prescribe
HAART – What will happen if congenital malformation is
confirmed with Efavirenz-based regimen?
• Possible candidates for pharmacokinetics studies – TMC125 : Etravirine– Inhibitor of integrase : Raltegravir
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PMTCT Future researchMore operational research
• Axis 1 : Evaluation of PMTCT program
• Axis 2 : Strategies to increase PMTCT coverage
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Evaluation of PMTCT program
Lack of clarity and consensus around how to monitor the effectiveness of PMTCT programmes
Need to validate a consensus model for PMTCT effectiveness monitoring
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Evaluation of PMTCT program in Africa
59%PMTCT coveragePearl Survey (2007)
60%PMTCT coverageUNAIDS (2011)
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Urgent need to find innovative strategies to increase HIV testing and PMTCT coverage
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1 000 000 pregnant women
Tested for HIV35%
(350,000)
Not Tested for HIV65%
(650,000)
HIV + (n=32, 500)
HIV+ (n=17,500)
HIV prevalence 5%
Pediatric HIV infection(n=13, 000)
40% of MTCT
Pediatric HIV infection(n=3, 500)
Pediatric HIV infection(n=175)
50% PMTCT
A B B+
Increase PMCT coverage• To identify best practices and barriers for
effective PMTCT services including HIV testing
• Evaluation of different strategies – Conditional cash transfers1
– Mobile phone or SMS reminder for adherence1
– Male partner involvment1
– Transport vouchers– Task-shifting from physicians to nurses /midwifes2
– Community implication
1. http://www.clinicaltrials.gov [PMTCT] 2. WHO 200724
Conclusions • End of the cycle of the clinical research on
PMTCT
• More operational research
• Research should focused more on PMTCT coverage
• Pharmacovigilance is urgent need to put in place
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Aknowlegements
• François Dabis, Bordeaux, France
• Xavier Anglaret, Bordeaux, France
• Patrick Coffie, Abidjan, Côte d’Ivoire
• Renaud Becquet, Bordeaux, France
• Serge Paul Eholie, Abidjan, Côte d’Ivoire
• Emmanuel Bissagnene, Abidjan, Côte d’Ivoire
• Serge Kanhon, Abidjan, Côte d’Ivoire
• Eugène Messou, Abidjan, Côte d’Ivoire
• Out team at the ANRS site in Abidjan Côte d’Ivoire
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