Prevention of Mother to Child Transmission of HIV

1
Prevention of Mother to Child Transmission of HIV

• George Kafulafula
• Dept of Obstetrics Gynaecology
• University of Malawi College of Medicine
• Society of Medical Doctors Medical Conference
• Sun Sand Holiday Resort, Mangochi
• August 22, 2009

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Outline

• Introduction
• Science of PMTCT
• Conclusions drawn from the science
• Malawi PMTCT ARV Regimens
• Concluding remarks

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Introduction

• Paediatric HIV peri-natally acquired
• PMTCT intervention to avert paediatric HIV
• Risk
• Breastfeeding population 40
• Non-breastfeeding population 25
• Intervention created dual nature of epidemic
• Industrialised countries lt 2
• Resource limited countries 10

4
Clinical Trials

• Randomised Controlled Trials gold standard
  evidence
• Meta-analysis
• Observational data
• Expert opinion

5
Perinatal Science

• PACTG 076 Trial
• Abbreviated regimes studies
• Thai regimen 1
• Thai regimen 2
• HIVNET 012 (Uganda)
• NVAZ (Malawi)
• SWEN
• PEPI-Malawi
• BAN (Lilongwe)
• Breastfeeding Associated HIV transmission Studies

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PACTG 076 Trial

• N Engl J Med 19943311173-80
• USA and France
• Non breastfeeding population
• AZT 25.5 vs 8.3 Placebo at 18months
• Efficacy 70
• Limited applicability in RLC
• Cost
• Complexity

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Abbreviated Regimen Trials 1

• Lancet 1999353773-80
• Thailand
• Non breastfeeding population
• 36 weeks gestation
• AZT 9.4 vs 18.9 Placebo
• Efficacy 50 at 6 months

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Abbreviated Regimen Trials 2

• N Engl J Med 2004351217-28
• Thailand
• Non breastfeeding population
• 28 weeks gestation
• AZT sd-NVP 1.1 vs 6.3 AZT alone
• Efficacy 80 at 6 months

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Abbreviated Regimen Trials 3

• Lancet 1999362859-68
• HIVNET 012 (Uganda)
• Breastfeeding population
• Late presenters
• sd-NVP 11.8 vs 20.0 at 18 months
• Efficacy 41

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Abbreviated Regimen Trials 4

• Lancet 20033621171-7
• NVAZ (Malawi)
• Late presenting, Breastfeeding population
• Sd-NVP 15.3 vs 20.0 at 8 weeks
• Efficacy 36

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Abbreviated Regimens Trials 5

• Lancet 20023591178-86
• South Africa, Uganda and Tanzania
• Breastfeeding population
• AZT 3TC vs Placebo 15.3
• AP/IP/PP 5.7 Efficacy 63
• IP/PP 8.9 Efficacy 42
• IP 14.2

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Conclusions

• Several ART regimens efficacious to prevent
  antepartum and intrapartum MTCT
• Difficult to compare
• Population diversity
• Duration of admimistration
• Breastfeeding mode
• Different clades of HIV

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Conclusions

• Combination ART more effective than monotherapy
• AZT vs AZT sd-NVP, AZT 3TC
• Sd-NVP vs AZT alone, AZT 3TC
• Longer courses more efficacious (Petra)
• IP/PP AZT/3TC vs sd-NVP have similar efficacy
  (SAINT Trial)
• If AP course is lt4 wks, longer infant prophylaxis
  may be more efficacious

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Conclusions

• Breastfeeding diminishes efficacy of regimes
• Diminution less with NVP vs AZT/3TC
• Sd-NVP boosts efficacy of short course
• Short course regimes for PMTCT are as good as
  HAART for women who do not qualify for HAART
• Repeat sd-NVP in subsequent pregnancy is
  efficacious

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Sd-NVP Resistance

• Disadvantage of long half life of NVP
• Rates of mutations high in early period
• Wanes with time
• Unknown clinical significance
• Risk factors
• 3TC/AZT IP PP for 7 days reduces resistance
  from 60 to 10

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Infant Prophylaxis Studies

• SWEN Study
• 6 weeks of NVP in breastfeeding infants
  significantly decreased postnatal MTCT by 46 at
  6 weeks
• PEPI Malawi
• 3 months of NVP reduces HIV transmission 65
• BAN (Malawi)
• 6 months
• HPTN 046 (Zimbabwe, Tanzania, Uganda)
• Ongoing 6 months prophylaxis

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Malawi PMTCT Regimens

• Mother on HAART
• Continue HAART antepartum (AP), Intrapartum (IP)
  and Postpartum (PP)
• Infant AZT
• 7 days if Mother on HAART at least 4 weeks
• 4 weeks if Mother on HAART lt 4weeks

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Malawi PMTCT Regimens

• Mother not HAART eligible
• AP AZT from 28 weeks gestation till labour
• IP sd-NVP plus AZT/3TC at onset of labour
• PP AZT/3TC for 7 days
• Infant
• sd-NVP
• AZT for 7 days
• AZT for 4 weeks if mother
• Diagnosed IP/PP and therefore did not receive ARV
• Had AZT/3TC for less than 4 weeks

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Doctors explanation of diagnostic tests to
patients
of respondents
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COMING SOON! IMPAACT Strategy Perinatal
Protocol PROMISE (P1077) Promoting
Maternal-Infant Survival Enhancement BF FF HS
Components