Prevention of Mother to Child Transmission of HIV: 2012 pdf

Scenarios: 3 women presenting in labour at 37 wks gestation combination ART since 15 wks gestation, viral load... YEAR ETHNICITY PRE-CONCEPTION / ANTENATAL HIV TEST LEVEL of OB CARE I

Disclosure

recommendations for women in pregnancy (antepartum,

intrapartum) to prevent MTCT-HIV

management to prevent MTCT-HIV

Scenarios: 


3 women presenting in labour at 37 wks gestation

combination ART since 15 wks gestation, viral load

<40 copies/mL

since 15 wks gestation but incompletely adherent to therapy, viral load 2,500 copies/mL

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

feeding

Breast-Fowler et al Clin Perinatol 2010;37(4):721-37

Prevention of MTCT-HIV

cohort

q   antenatal ART > 4 wk prior to delivery: 1.6%

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

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

q  HIV testing part of routine care 1

q   Repeat testing if ongoing risk 1

q   Maternal care: antenatal + intrapartum

q   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

Early Postpartum (0-6 months)

Proportion of infections

http://www.aidsinfo.nih.gov/

Antepartum Care

regardless of CD4 count / viral load

q   < 350: ASAP even in first trimester

q   350-500: consider starting ASAP even in first trimester

q   > 500: after first trimester

DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf Accessed Mar 6, 2012

Antenatal cART (2 NRTI + 1 PI or 1 NNRTI)

Zidovudine Nevirapine CD4<250 Atazanavir

Lamivudine Efavirinz avoid1-tri Lopinavir

Tipranavir Indinavir

Entry Inhibitor

Maraviroc Enfuvirtide

Combinations

Combivir (ZDV-3TC)

Kivexa Truvada

Kaletra (LPV/r)

Complera

Integrase inhibitor

Raltegravir

Antepartum cART

q  Target < 1,000 copies/mL

q   Ideal undetectable < 40 copies/mL

Viral Load (copies/mL) Transmission rate (%)

> 100,000 63% 1

< 1,000 (not on ART) 9.8% (95% CI 7.0-13.4%)2

< 1,000 (on ART) 1% (95% CI 0.4%-1.9%)2

1 Garcia PM et al New Engl J Med 1999;341:394-402

2 Ioannadis JP et al JID 2001;183(4):539-45

Intrapartum Care: Mode of Delivery

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 ART

q   Initiate IV Zidovudine:

PACTG 076 Landmark trial

•  MC, R, DB, PC trial

•  Pregnant women (14-34 wks), CD4>200, formula feeding

•  ZDV (antenatal 100 mg PO 5/day + Intrapartum 2mg/kg IV load + 1mg/kg infusion + infant 2 mg/kg PO Q6H x 6wks) vs Placebo

•  Transmission: ARR 17.2% (8.3 vs 25.5%) p<0.05, RRR 67%

Connor et al, New Engl J Med 1994;331:1173-80

Connor et al NEJM 1994;331:1173-80

3

Add single dose nevirapine

Initiate:

@ onset of labour or

@ rupture of membranes

@ > 2-3 h pre-c/s until clamping cord

Intrapartum Care: Role for single dose NVP

1 Guay et al Lancet 1999; 354: 795-802

2 Cunningham CK et al J Infect Dis 2002;186(2):181-8

Mitigating Risk of single dose NVP

•   Long t1/2 = monotherapy with agent with low barrier to resistance

•   3TC-ZDV (Combivir ® ) 1 tablet PO twice daily x 7 days

Van Dyke et al

Clin Infect Dis 2012

None vs 7-d CBV/ DDI /Kaletra vs.30-d CBV/DDI vs 30-d CBV/

DDI/Kaletra

sequencing + OLA

Combivir/CBV = lamivudine (3TC)-zidovudine, Truvada = emtricitabine (FTC)-tenofovir, DDI = didanosine, Kaletra = lopinavir/ritonavir, OLA = oligonucleotide ligation assay

McIntyre et al PLoS Medicine 2009;6(10):e1000172

Intrapartum Care: Unknown HIV serology

HIGH LOW

Indeterminate Non-­‐reacJve

Postpartum Care

•   ART

•   Continue oral ART (unless otherwise indicated)

•   If SdNVP in labor give 3TC-ZDV (Combivir ® ) 1 tab PO BID x 7d

•   OI prophylaxis2

•   CD4 < 200: PCP (Cotrimoxazole DS, Dapsone)

•   CD4 < 50: MAC (Azithromycin)

•   Infant Feeding3,4

•   Breastfeeding contraindicated: exclusive formula feeding

•   Postnatal transmission risk: 0.9% per month

1 DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf Accessed Mar 6, 2012

2 CDC MMWR Recomm 2009 Rep Available at: http://www.cdc.gov/mmwr/pdf/rr/rr5804.pdf Accessed November 17, 2011

3 MacDonald NE Paediatr Child Health 2006;11(8):489-91

4 Coutsoudis et al Journal of Infect Dis 2004;

Infant Care : in*low* risk settings

q   PACTG 076 regimen

q   Zidovudine 2 mg/kg PO Q6H x 6 weeks

q   Reduced doses for premature infants (<35 weeks)

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

6-wks oral zidovudine beginning 6-12 hrs after delivery

DHHS NIH Perinatal guidelines 2011 http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf Accessed Mar 6, 2012

>35 wks 4 mg/kg/dose PO q12h for total 6

<29 wks 2 mg/kg/dose PO q12h for 4 wks then

2 mg/kg/dose PO q8h for 6 wks 1.5 mg/kg/dose IV q12h for 4 wks then 1.5 mg/kg/dose IV q8h for 4

Infant Care : in *high* risk settings

Wade et al New Engl J Med 1998;339(20):1409-14.

No ante- or intrapartum ART

no ZDV

26.6%

ZDV within 48hr x 6wk

9.2%

ZDV at > 3 day x 6wk

Mother

Infant

HIV

Design R, open-label, MC

Population N=1704 with single positive rapid HIV test not on

antenatal ART, median log VL 4.17, CD4 464 41% IV ZDV, 65% vaginal delivery

Infant care summary

Infant Antiretroviral Dosing

Infant Testing

q   Diagnostic HIV-PCR

q   At birth,

q   2 weeks (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 at 37 wks gestation

cART since 15 wks gestation, viral load <40 copies/

mL

cART since 15 wks gestation but incompletely

adherent to therapy, viral load 2,500 copies/mL

medications, IVDU throughout pregnancy

Scenarios: 


3 women presenting in labour at 37 wks gestation

since 15 wks gestation, viral load <40 copies/mL

Scenarios: 


3 women presenting in labour at 37 wks gestation

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

q  Rapid HIV Antibody test if available

q  ? Caesarian section

q  Initiate IV ZDV + single dose NVP + 1-week 3TC-ZDV

q  Infant – combination ART (ZDV x 6wk + 3-dose NVP + 2-wk 3TC) q  Avoid breastfeeding

Scenarios: 


3 women presenting in labour at 37 wks gestation

References

Fowler et al Clin Perinatol 2010;37(4):721-37

Forbes JC et al AIDS 2012;26:DOI:10.1097/QAD.0b013e328350995

Keenan-Lindsay et al J Soc Obstet Gynaecol Can 2006; 185:1103-7

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

Garcia PM et al New Engl J Med 1999;341:394-402

Ioannadis JP et al JID 2001;183(4):539-45

Legardy-Williams et al Clin Perinatol 2010;37(4):777-85

Connor et al, New Engl J Med 1994;331:1173-80

Guay et al Lancet 1999; 354: 795-802

Cunningham CK et al J Infect Dis 2002;186(2):181-8

Chaix et al J Infect Dis 2006;193;482-7

Chi et al AIDS Res Hum Retroviruses 2009;25(11):1099-1106

McIntyre et al PLoS Med 2009;6(10):e1000172.p1-9

Arrive et al AIDS 2010;24:2481-8

Van Dyke et al Clin Infect Dis 2012; 54(2):285-93

Comtru Trial http://clinicaltrials.gov/ct2/show/NCT00346567

BCCDC Communicable Disease Control; Point of Care HIV Test Guidelines for Health Care Settings May 2011;1-38 Available at:

Centers for Disease Control and Prevention (CDC) MMWR Recomm Rep April 10 2009;58(RR-4):1207;quiz CE201-204 Available at:

MacDonald NE Paediatr Child Health 2006;11(8):489-91

Coutsoudis et al Journal of Infect Dis 2004;

Wade et al New Engl J Med 1998;339(20):1409-14

Neilsen-Saines et al 18 th Conference on Retroviruses and Opportunistic Infections Boston MA, 2011, Abs 124LB