De la prévention à l élimination, le chemin parcouru en matière de transmission verticale. De la recherche aux recommandations OMS

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1 De la prévention à l élimination, le chemin parcouru en matière de transmission verticale De la recherche aux recommandations OMS 16 novembre, 2011 Pr François DABIS Bordeaux

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3 (1)

4 (1) : EMTCT = ETME

5 The ETME Team, Kigali

6 : ANRS 049a DiTraME = PMTCT

7 ETME DiTraME etme

8 Outline Context Risk factors of HIV transmission through breastfeeding Alternatives to prolonged and unrestricted breastfeeding 2010 WHO PMTCT international recommendations What s next? emtct!!! The global picture of biomedical prevention

9 PMTCT Context Risk factors of HIV transmission through breastfeeding Alternatives to prolonged and unrestricted breastfeeding 2010 WHO PMTCT international recommendations What s next? emtct!!! The global picture of biomedical prevention

10 Over new HIV infections per day in 2009 worldwide 97% are in low and middle income countries are in children <15 years of age ( in 2009) are in adults: 51% are among women 41% are among young people (15-24)

11 Estimate of the annual number of infant infections averted through the provision of antiretroviral prophylaxis to HIV-positive pregnant women, globally, / Infant infections averted

12 PMTCT Risk factors of HIV transmission through breastfeeding: breastfeeding pattern (mixed, predominant, exclusive) breastfeeding duration

13 Mother-to to-child transmission of HIV (MTCT) timing of transmission Peri-partum transmission 15-30% Postnatal transmission 10-20%

14 Mother-to to-child transmission of HIV (MTCT) A public health challence in Africa High prevalence of HIV infection among young women High fertility HIV serostatus infrequently known before pregnancy/delivery Breastfeeding is the common practice, usually >12 months

15 How can we prevent postnatal HIV transmission in Africa? 1. Modification of infant feeding practices Reduction of the breastfeeding duration Replacement feeding from birth Early weaning Improvement of the breastfeeding patterns 2. Antiretroviral interventions during breastfeeding

16 Modification of infant feeding practices Positive results in one study (ANRS 1202 Ditrame Plus, Abidjan, Côte d Ivoire) d Good social acceptability of replacement feeding and early cessation of breastfeeding Moderate morbidity/mortality risk according to infant feeding practices Low postnatal risk of HIV transmission but not really feasible in most settings+++ Similar results were observed in well designed and controlled studies in Kenya, Botswana, and rural South Africa but not elswehere (Botswana and Zambia in particular) Nutritional adequacy of complementary feeding taking over breast milk: repercussions on infant growth

17 Courtesy of J. Stringer (CIDRZ, Lusaka) 17

18 How can we prevent postnatal HIV transmission in Africa? Alternatives to prolonged breastfeeding Antiretroviral interventions during breastfeeding Objective: Acting on the factors linked to the risk of HIV transmission

19 Antiretroviral interventions during breastfeeding The level of evidence is now good enough to translate research findings into public health practice Maternal treatment with triple ART works for PMTCT Maternal prophylaxis works too +++ Neonatal and infant post-exposure prophylaxis has now be proven to prevent the risk of acquisition of HIV via breast milk during <6months

20 6-week postpartum MTCT risk in women in need of ART Côte d Ivoire ANRS Ditrame, Ditrame Plus, MTCT-Plus Dabis Lancet 1999, Dabis AIDS 2005, Tonwe-Gold PLOS Med 2007 ART eligibility: WHO stage 3/4 and CD4<350/mm 3 or stage 1/2 and CD4<200/mm 3 (ART = ZDV or d4t / 3TC / NVP)

21 The best available triple ARV prophylactic regimens prevent most cases of MTCT in African populations Trial (Publication) ARV regimen Time of measurement Transmission rate Mma Bana Bostwana NEJM NRTI ZDV + 3TC + ABC vs ZDV + 3TC + LP/r > 200 CD4 M6 2.1% 0.4% Kesho Bora Burkina Faso, Kenya, SA Lancet Infect Dis 2011 KiBS Kenya PLOS Med 2011 ZDV + 3TC + LP/r CD4 ZDV + 3TC + NVP or NFV CD4 500 CD4 M6 4.9% M6 3.8% 3.3%

22 Antiretroviral interventions during breastfeeding ARV prophylaxis for HIV-exposed children SWEN Study Group Lancet 08

23 Outline Context Risk factors of HIV transmission through breastfeeding Alternatives to prolonged and unrestricted breastfeeding 2010 WHO PMTCT recommendations What s next? emtct!!! The global picture of biomedical prevention

24 New HIV recommendations to improve health, reduce infections and save lives Antiretroviral therapy for HIV infection in adults and adolescents 2. Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants 3. WHO principles and recommendations on infant feeding in the context of HIV 4. Antiretroviral therapy for HIV infection in children

25 Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants

26 Guiding principles Women (including pregnant women) in need of ARVs for their own health should get life-long ART Antenatal CD4 is critical for decision-making about ART eligibility Interventions should aim to maximize reduction of vertical transmission, minimize side effects for mothers and infants, and preserve future HIV treatment options Effective postpartum ARV-based interventions for all women will allow safer breastfeeding practices Simple, unifying principles needed for different country settings

27 Antiretroviral therapy (ART) Women with CD4 <350 regardless of clinical stage Women with clinical stage 3 or 4 (symptomatic) regardless of CD4 Start ART as soon as feasible regardless of gestational age ± 1/3 all HIV-positive pregnant women Strong recommendation

28 ARV prophylaxis to prevent MTCT For women not eligible for ART or unknown eligibility: ± 2/3 all HIV-positive pregnant women Begin as early as 14 weeks of gestation (2 nd trimester) or as soon as possible thereafter Strong recommendation

29 What ARV prophylaxis to give to non-eligible pregnant women 2 possible options: A) Maternal AZT B) Maternal triple ARV prophylaxis without NVP Each of these prenatal /delivery option will be followed by postnatal prophylaxis either to the mother or to the baby Strong recommendation

30 Prophylaxis options for non ART-eligible women and infants Option A Mother Antepartum AZT (from 14 weeks) sd-nvp at onset of labour* AZT + 3TC during labour & delivery* AZT + 3TC for 7 days postpartum* Infant Breastfeeding population Daily NVP (from birth until one wk after all exposure to breast milk had ended) Non-breastfeeding population AZT for 6 weeks OR NVP for 6 weeks Option B Mother Triple ARV (from 14 wks until one wk after all exposure to breast milk has ended) AZT + 3TC + LPV-r AZT + 3TC + ABC AZT + 3TC + EFV TDF + XTC + EFV Infant Breastfeeding population Daily NVP from birth to 6 weeks Non-breastfeeding population AZT for 6 weeks OR NVP for 6 weeks *sd-nvp and AZT+3TC can be omitted if mother receives > 4 wks AZT antepartum

31 Does A = B? Option A, Option B Is A > B? Is B > A? Alternatives to A and B?

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33 La recherche française sur le sida bloquée par des problèmes d'assurance PARIS, 4 mars 2011 (AFP) L Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) a dû suspendre des essais dans les pays du sud sur la transmission du virus du sida de la mère à l'enfant, faute d'assurance, a annoncé vendredi son Directeur, le Pr. Jean-François Delfraissy.

34 Infant feeding in the context of HIV

35 HIV & breastfeeding: 2009 key recommendation Which breastfeeding practices and for how long Mothers know to be HIV-infected (and those whose infants are uninfected or of HIV unknown status) should exclusively breastfeed for the firs 6 months, introducing complementary foods thereafter and continue breastfeeding for the first 12 months of life Breastfeeding should then only stop once a nutritionally adequate and safe diet without breast milk can be provided Strong recommendation, high quality of evidence for first 6 months

36 PMTCT Context Risk factors of HIV transmission through breastfeeding Alternatives to prolonged and unrestricted breastfeeding 2010 WHO PMTCT international recommendations What s next? emtct!!! The global picture of biomedical prevention

37 The challenge of the PMTCT cascade in Africa and elsewhere (A) Attend institutional antenatal care (B) Be offered VCT (C) Accept VCT (D) Obtain results (E) Agree to ARV prophylaxis (F) Adhere to ARV prophylaxis (G) Adhere to infant ARV doses ANC antenatal care VCT voluntary counselling and testing CD4 testing ARV antiretroviral prophylaxis or treatment Retention

38 Courtesy of J. Stringer (CIDRZ, Lusaka) 38

39 PEARL study Overall cord blood results for nevirapine intake 2010; 304: % 75% NVP in cord blood of HIV positive 70% 60% 59% 56% 50% 40% 30% 20% 22% NVP in cord blood 10% 0% Cameroon S. Africa Ivory Coast Zambia

40 The response: emtct July 2011

41 emtct emtct = Saving lives of children and mothers

42 Maternal Universal ART Maternal ART + Maternal triple ARV prophylaxis

43 Time for a simpler, bolder approach courtesy of Tony Harries (CROI 2011, Boston)

44 Malawi Policy 2011 TDF + 3TC + EFV to all HIV-infected pregnant women for life regardless of CD4 count BORN HIV FREE

45 Malawi s New PMTCT Policy Advantages Simple to implement Minimizes vertical transmission Protects for the next pregnancy Improves maternal health and survival Reduces sexual transmission Reduces risk of tuberculosis Treats hepatitis B co-infection

46 Malawi s New PMTCT Policy Simple to implement Minimizes vertical transmission Protects for the next pregnancy Improves maternal health and survival Reduces sexual transmission Reduces risk of tuberculosis Treats hepatitis B co-infection Careful monitoring of acceptability, feasibility, outcomes and safety

47 A or B A and B (???) Regimen B+ is no longer a theoretical option WHO regimen Number of countries (list) Source: WHO (provisional July 2011) A 15 B 20 B+ Malawi South Africa? A and B 4

48 PMTCT Context Risk factors of HIV transmission through breastfeeding breastfeeding pattern (mixed - exclusive) breastfeeding duration Alternatives to prolonged and unrestricted breastfeeding 2010 WHO PMTCT international recommendations What s next? emtct!!! The global picture of biomedical prevention

49 The global PMTCT strategy Prevention of unwanted pregnancies among HIV+ women (Family Planning) Primary prevention of sexual transmission of HIV among sexually active aduts / women of childbearing age / pregnant women Antenatal VCT PMTCT pregnancy delivery postnatal period HAART (access & use) Medical and psychosocial care Uninfected mothers and children should remain in this serostatus

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51 What is prevention today? A, B, C 3, M, P 2, S, T, V,

52 - Abstinence - Be faithful - Condom - (male) Circumcision - Counselling & Testing - Microbicides - Post-exposure prophylaxis - Pre-exposure prophylaxis - Sexually transmitted infections - (antiretroviral) Treatment Vaccination

53 Source: Abdool Karim, May 2011 Exposure prophylaxis PEP PrEP Ref: Schechter, Grant Microbicides Ref: Abdool Karim Treatment for prevention HIV Counselling and Testing (HCT) Ref: Coates Behavioural Intervention - Abstinence - Be Faithful - Condoms HIV PREVENTION Vaccines Ref: Rerks-Ngarm Male circumcision Ref: Auvert, Gray & Bailey Screening & treatment of STIs Ref: Grosskurth Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included this is focused on reducing sexual transmission

54 ART: potentially more efficacious (than any of the previously evaluated prevention methods)

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56 HPTN 052 Intermediate results Cohen MS et al. NEJM 2011;365: Transmissions: 1 vs 27 cases (96% reduction) after >2 years of follow-up 1. Extra-pulmonary tuberculosis: 3 vs 17 cases 2. Severe morbidity and mortality: 40 vs 65 events (41% reduction) «HPTN 052 provides compelling evidence for a new HIV prevention approach that links prevention and care efforts»

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58 Acknowledgements Abidjan: Didier Koumavi Ekouevi, Patrick Coffié Bordeaux: Elise Arrivé, Renaud Becquet Lusaka: Jeffrey Stringer Special thanks to Nathan Shaffer (WHO)

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