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
1985 1997 (1)
1985 1997 (1)
1985 1997 (1) : EMTCT = ETME
The ETME Team, Kigali
1998 2010: ANRS 049a DiTraME = PMTCT
1985 2010 ETME DiTraME etme
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
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
Over 7 000 new HIV infections per day in 2009 worldwide 97% are in low and middle income countries 1 000 are in children <15 years of age (370 000 in 2009) 6 000 are in adults: 51% are among women 41% are among young people (15-24)
Estimate of the annual number of infant infections averted through the provision of antiretroviral prophylaxis to HIV-positive pregnant women, globally, 1996 2008 70 000 65 000 / 370 000 60 000 Infant infections averted 50 000 40 000 30 000 20 000 10 000 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
PMTCT Risk factors of HIV transmission through breastfeeding: breastfeeding pattern (mixed, predominant, exclusive) breastfeeding duration
Mother-to to-child transmission of HIV (MTCT) timing of transmission Peri-partum transmission 15-30% Postnatal transmission 10-20%
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
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
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
Courtesy of J. Stringer (CIDRZ, Lusaka) 17
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
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
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)
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 2010 3 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 200 500 CD4 ZDV + 3TC + NVP or NFV 350 500 CD4 500 CD4 M6 4.9% M6 3.8% 3.3%
Antiretroviral interventions during breastfeeding ARV prophylaxis for HIV-exposed children SWEN Study Group Lancet 08
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
New HIV recommendations to improve health, reduce infections and save lives 2010 1. 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
Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants
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
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
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
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
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
Does A = B? Option A, Option B Is A > B? Is B > A? Alternatives to A and B?
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.
Infant feeding in the context of HIV
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
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
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
Courtesy of J. Stringer (CIDRZ, Lusaka) 38
PEARL study Overall cord blood results for nevirapine intake 2010; 304: 293-302 302 80% 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
The response: emtct July 2011
emtct emtct = Saving lives of children and mothers
Maternal Universal ART Maternal ART + Maternal triple ARV prophylaxis
Time for a simpler, bolder approach courtesy of Tony Harries (CROI 2011, Boston)
Malawi Policy 2011 TDF + 3TC + EFV to all HIV-infected pregnant women for life regardless of CD4 count BORN HIV FREE
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
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
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
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
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
What is prevention today? A, B, C 3, M, P 2, S, T, V,
- Abstinence - Be faithful - Condom - (male) Circumcision - Counselling & Testing - Microbicides - Post-exposure prophylaxis - Pre-exposure prophylaxis - Sexually transmitted infections - (antiretroviral) Treatment Vaccination
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
ART: potentially more efficacious (than any of the previously evaluated prevention methods)
HPTN 052 Intermediate results Cohen MS et al. NEJM 2011;365: 493-505 1. 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»
Acknowledgements Abidjan: Didier Koumavi Ekouevi, Patrick Coffié Bordeaux: Elise Arrivé, Renaud Becquet Lusaka: Jeffrey Stringer Special thanks to Nathan Shaffer (WHO)
Francois.dabis@isped.u-bordeaux2.fr