Prevention of Mother to Child Transmission of HIV: 2012 Karen Tulloch, BSc(Pharm), ACPR, PharmD Disclosure !  No declarations Learning Objectives !  To understand the mechanism of mother to child transmission (MTCT) of HIV !  To understand the key points of intervention to prevent MTCT of HIV !  To be aware of the antiretroviral drug therapy (ART) recommendations for women in pregnancy (antepartum, intrapartum) to prevent MTCT-HIV !  To be aware of the ART recommendations for infant management to prevent MTCT-HIV Scenarios: 
 3 women presenting in labour at 37 wks gestation •  36 yr old female, known HIV infection, receiving combination ART since 15 wks gestation, viral load <40 copies/mL •  36 yr old female, known HIV infection, receiving cART since 15 wks gestation but incompletely adherent to therapy, viral load 2,500 copies/mL •  36 yr old female, unknown HIV status, no prenatal care, no known medications, IVDU throughout pregnancy Mother to Child Transmission of HIV: 
 Timing & mechanisms of transmission HIV infected woman passes virus onto baby In utero infection At time of labor and delivery Breast- feeding Fowler et al. Clin Perinatol 2010;37(4):721-37. Prevention of MTCT-HIV ! Canadian Perinatal Data ! 2692 mother infant pairs identified in prospective cohort ! Rate of vertical transmission ! 1990-1996: 20.2% ! 1997-2010: 2.9% !  antenatal ART > 4 wk prior to delivery: 1.6% !  maternal HAART > 4 wk prior to delivery: 0.4% Prevention of MTCT-HIV
 Canadian Perinatal HIV Surveillance Data 2692 mother infant pairs identified in prospective cohort If initiated > 4 wks prior to delivery: 0.4% Forbes JC et al. AIDS 2012;26(6):757-63. !"#$%"&'(&)*%+&%,-%.//0123.3 YEAR ETHNICITY PRE-CONCEPTION / ANTENATAL HIV TEST LEVEL of OB CARE IVDU in PREGNANCY 1 2008 caucasian Positive test – no care poor yes 2 2006 aboriginal Pre-conception – negative intermittent no 3 2001 aboriginal No test poor yes 4 2001 Black Antenatal - negative regular no 5 2000 caucasian Antenatal - negative regular no 6 1998 south asian No test regular no 7 1998 south asian Antenatal – negative regular no 8 1997 aboriginal Antenatal - negative regular yes Principles to Prevent MTCT-HIV !  Prevent acquisition of HIV !  Prevent unintended pregnancies !  Diagnose infection during pregnancy !  HIV testing part of routine care 1 !  Repeat testing if ongoing risk 1 ! Prevent HIV transmission to infant ! Maternal care: antenatal + intrapartum ! Infant care: pre/post exposure prophylaxis + prevent ongoing exposure (breastfeeding) WHO PMTCT Strategic Vision 2010. http://www.who.int/hiv/pub/mtct/strategic_vision.pdf. Accessed Mar 6, 2012 DHHS NIH Perinatal guidelines 2011. http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf. Accessed Mar 6, 2012 1 Keenan-Lindsay et al. J Soc Obstet Gynaecol Can 2006; 185:1103-7. Timing of MTCT with Breastfeeding & No Antiretroviral Prophylaxis 0% 20% 40% 60% 80% 100% Early Antenatal (<36 wks) Late Antenatal (36 wks to labor) Labor and Delivery Late Postpartum (6-24 months) Early Postpartum (0-6 months) Proportion of infections http://www.aidsinfo.nih.gov/ [...]... q IV preparation available in unable to tolerate oral q  2012 change: Twice daily dosing (4 mg/kg Q12H) if > 35 weeks q  Initiate as soon as possible (6-12 hrs of delivery) q  Toxicity: q transient anemia/neutropenia q consider shortened course (4 vs 6 wks) DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL .pdf Accessed Mar 6, 2012 Infant Care in*low* risk settings... breastfeeding •  Intrapartum/Infant ZDV vs sdNVP •  Mother ZDV 300mg PO q3h + Infant ZDV 4mg/kg BID x 7day •  Mother sdNVP 200mg PO x 1 + Infant sdNVP 2mg/kg at 72hr •  Transmission: ARR 12% (13.1 vs 25.1%, p=0.0006), RRR 47% Connor et al, New Engl J Med 1994;331:1173-80 •  19% evidence of NVP mutations q PACT 3162: no benefit to addition sdNVP to antenatal combination ART 1Guay 2Cunningham et al... month 1DHHS 2CDC NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL .pdf Accessed Mar 6, 2012 MMWR Recomm 2009 Rep Available at: http://www.cdc.gov/mmwr /pdf/ rr/rr5804 .pdf Accessed November 17, 2011 3MacDonald NE Paediatr Child Health 2006;11(8):489-91 4Coutsoudis et al Journal of Infect Dis 2004; Infant Care: in*low* risk settings q  PACTG 076 regimen q Zidovudine 2 mg/kg... JID 2001;183(4):539-45 Intrapartum Care: Mode of Delivery q Known HIV infection: q  Assess recent viral load (known or projected) q  Determine mode of delivery Vaginal Elective* Caesarian (38wks) On ART and VL 1000 copies/mL *Before the onset of labour *Prior to rupture of membranes Legardy-Williams et al Clin Perinatol 2010;37(4):777-85 Intrapartum Care: Intrapartum... therapy (cART) to ALL women regardless of CD4 count / viral load q Timing of initiation depends on CD4 count q  < 350: ASAP even in first trimester q 350-500: consider starting ASAP even in first trimester q > 500: after first trimester q Begin by 28 weeks at the latest through delivery   DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL .pdf Accessed Mar 6, 2012 Antenatal... Etravirine Ritonavir Tenofovirbone? Rilpivirine Nelfinavir Emtricitabine Integrase inhibitor Darunavir Didanosine Stavudine Raltegravir Entry Inhibitor Fosamprenavir Saquinavir Maraviroc Tipranavir Enfuvirtide Indinavir Combinations Combivir (ZDV-3TC) Kivexa Truvada Kaletra (LPV/r) Atriplaavoid1-tri Complera Antepartum cART q  Decrease maternal viral load (blood, genital) Viral Load (copies/mL) Transmission. .. (optional in low risk), q  4 weeks (essential): transmission diagnosis, early d/c? q  2-4 months q  Uninfected: 2 negative HIV PCR at > 1 month of age q  Infected: 2 positive HIV PCR are diagnostic q  HIV-Antibody (EIA) q  To document seroconversion DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL .pdf Accessed Mar 6, 2012 Scenarios: 
 3 women presenting in labour... Toxicity: transient anemia/neutropenia consider shortened course (4 vs 6 wks) DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL .pdf Accessed Mar 6, 2012 Infant Care: in *high* risk settings Mother Infant HIV transmission No ante- or intrapartum ART no ZDV ZDV within 48hr x 6wk ZDV at > 3 day x 6wk 26.6% 9.2% 18% 18% Wade et al New Engl J Med 1998;339(20):1409-14 HPTN... immunoassay  &  western  blot)       • 8.3%  (13) of  infants  infected  in  the  zidovudine  group  and   25.5%  (40)  in  placebo  group     Connor et al NEJM 1994;331:1173-80 ALL WOMEN: IV ZDV 2mg/kg IV bolus + 1mg/kg/hr IV infusion On antenatal ART (regardless of viral load) Continue oral ART No additional ART Initiate: @ onset of labour or @ rupture of membranes @ > 2-3 h pre-c/s until clamping cord... Hum Retroviruses 2009 TOPS:McIntyre et al PLoS Med 2009 Arrive et al sequencing AIDS 2010 Van Dyke et al Clin Infect Dis 2012 None vs 7-d CBV/ DDI /Kaletra 29.4% vs 1.8% vs 7.1% vs 5.3% consensus sequencing + OLA vs.30-d CBV/DDI vs 30-d CBV/ DDI/Kaletra Comtru Trial 7-d Combivir vs sd Truvada ongoing Combivir/CBV = lamivudine (3TC)-zidovudine, Truvada = emtricitabine (FTC)-tenofovir, DDI = didanosine, . !  To understand the mechanism of mother to child transmission (MTCT) of HIV !  To understand the key points of intervention to prevent MTCT of HIV. Prevention of Mother to Child Transmission of HIV: 2012 Karen Tulloch, BSc(Pharm), ACPR, PharmD