Welcome to I-TECH HIV/AIDS Clinical Seminar Series

September 25, 2008

Mother to Child Transmission of HIV

Grace John Stewart MD, PhD

Overview

• Diagnosis of HIV during pregnancy

• PMTCT

• Infant feeding

• Infant diagnosis

• Post-PMTCT

Case 1

• 19 year old coming to maternal child health clinic, doesn’t know HIV status. Who should offer testing? a) physician

b) nurse

c) counselor

Case 1

How should pre-test and post-test counseling be approached?

a) Ask women if they would like an HIV test after pre-test counseling

b) Provide results the next weekc) When the HIV diagnosis news is given, focus on

encouragement, book next appointment to discuss PMTCT

d) Discuss PMTCT the day the mother is diagnosed with HIV

‘Opt-out’ routine testing versus opt-in in Botswana

MMWR 2004; 53 (46): 1083-86

• Secondary school graduates 4 wk HIV-counseling training

• 10-15 minute group discussion/flip charts

• HIV transmission, PMTCT

• Routine testing, right to opt-out, results in a month

• At delivery 50% knew status in 2003 vs. 76% in 2004

Same day versus deferred resultsMalonza AIDS 2003; 17:113-118

• Same day results 96% received vs. 73% in deferred group

• Return for referral to PMTCT higher in deferred group (66% vs. 87%)

CounselingDelva AIDS Care 2006; 18 (3): 189-93

• 14 groups, 66 pre-test, 50 post-test in Mombasa, Kenya

• Time (similar between counselors)– group education 33 minutes – pre-test 6.6 mins – post-test positive 38 mins, post-test negative 7.6 mins (p<0.001)

• Content– window, risk reduction not discussed for negatives– emotional reactions, support not dealt with for positives

• Health information vs. counseling balance difficult to achieve

Documentation and confidentialityhttp://www.qaproject.org/news/03archives/newsarchives_stigmaRwanda.html

• Focus group discussions in Rwanda 2003

• Providers– fear exposure (sometimes test women without consent)– exposure precautions limited at sites– negative attitude towards HIV-positive women who choose to

become pregnant

• HIV-positive women– poor pre- and post-test counseling– violations of confidentiality– disrepect and passive rejection at labor

Case 1: Synopsis HIV testing during pregnancyUSPHS, CDC-GAP 2006

• Provider-initiated routine testing

• Essential PMTCT messages on first encounter

• Group pre-test

• Rapid HIV test, same day results

• Audits: perceptions of women and providers, quality of counseling, options to update

Case 2

• 26 year old in Malawi comes to hospital in labor, does not know her HIV status. She should be advised to:

a) Get HIV testing at 6 week postpartum visit

b) Be given NVP

c) Get testing during labor, and ART if HIV positive

HIV testing in laborPai PLoS Med 2008, Homsy JAIDS 2006

• 24 hour HIV testing in labor, 99% acceptable in rural India

• Uganda 66% advanced labor, 84% offered testing, 6% opted out– more partners at

delivery than at ANC with 97% HIV tested

Case 3

• 25 year old, HIV diagnosed in pregnancy, CD4 400 cells/mm3 what regimen should she receive and for how long?

Current WHO guidelines

Use of a ‘tail’

McIntyre IAS 2004; Chi, Lancet 2007;370:1698-705

• TOPS trial South Africa (McIntyre IAS 2004)– NVP 9/18 (50%) NNRTI res– NVP plus 3TC/ZDV 4/43 (9.3%) NNRTI res

• p=0.001

• Tenofovir/emtricitabine Zambia – NVP 41/166 (25%) NNRTI

res– NVP/TFV/FTC 21/173 (12%) NNRTI res

• p=0.002

Maternal HAART and infant prophylaxisTransmission between 4/6 wks and 6 months

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TR 4/6 wk to 6 mo

Case 4

• 28 year old pregnant HIV-infected mother has not told partner she has HIV. Should he be notified? How?

Couples counselingFarquhar JAIDS 2004;37:1620-26

• Partner VCT or couples VCT increased– NVP uptake– NVP compliance– No BF

Couples counselingFarquhar JAIDS 2004;37:1620-26

• Partner VCT or couples VCT increased– NVP uptake– NVP compliance– No BF

Domestic Violence and PMTCT

Kiarie AIDS 2006;20 (13):1763-1769 •2,836 women at antenatal clinics, 331 male partners

-28% baseline domestic violence (DV) (20% physical)-women with baseline DV had increased odds of HIV-previous DV did not decrease VCT uptake-0.9% reported post-test DV- HIV-1 -seropositive women who notified partner 4.8 fold-

more DV than HIV-seronegative

-Male/female concordance in reporting

Domestic violence cofactors:polygamy, STD, HIV, crowding, income, earlier sex, non-formal marriage, lower education

Case 5

• 22 year old HIV-infected woman lives in slum, shared tap, shared toilet, should she formula feed or breastfeed her infant?

Antiretrovirals make BF saferNduati JAMA 2000; Thior JAMA 2006; Tonwe-Gold PLoS Med 2007

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BF vs FF

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FF

Nduati, JAMA 2000

Thior, JAMA 2006

•HAART in BF: <~5% TR

•Tiered approach (HAART CD4<200, ZDV/NVP): 5.7% TR

S Africa

2001Coutsoudis

Zimbabwe

2005Iliff

S Africa

2007Coovadia

Zambia

2008Kuhn

EBF by 6 months 4% 7.6% 40% 84% to 4 months

EBF definition Only BF (x meds)

At least 2 of 3 time-points

Up to 3 days Only BF (x meds)

HIV btwn 6 wks & 6 mos

MBF

EBF

2.5%

4.4%

4.4%

1.3%

? 1.8-11-fold 4%

4 mos

10%

4%

HIV btwn 6 wks & >15 mos

MBF

EBF

14.0%

9.7%

13.9%

6.9%

NA NA

Exclusive Breastfeeding

Realities of EBF

• Intention for EBF but cultural pressure to MBF

• Plans after 6 months?• Working mothers• Feeding counseling poor• Extended maternal/infant

separation at delivery in some settings (Durban median 11 hours to first BF)

Exclusive Breastfeeding Conclusions

• Should be promoted for all women

• HIV-targeted counseling may be redundant

• Implementation challenges– Counseling– Cessation– Approach after lapse in EBF

Issues

Formula Exclusive breastfeeding

Safety Stopping at 6 months

Cost Difficult to implement

Confidentiality Risk of HIV with early mixed feeding

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GE rate VTGE rate KiBS

CDC-HAART KIBS StudyKisumu, Kenya

Age in months

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1 mo 3 mo 6mo 9mo 12mo

KiBSVT

Age in months

VT Study

N=440 KiBS

N=63

GE hospitalizations Growth failure

Slide courtesy Mary Glenn Fowler and Tim Thomas

Zambia Exclusive Breastfeeding StudyCROI 2007; Kuhn NEJM 2008

•HIV-free survival comparable for abrupt wean and indefinite breastfeeding

Risk of infant HIV-1 or death among infants uninfected at 3-7 months then followed for 18-24 months

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Changes in WHO consensus statement

2000 2006

“when replacement feeding is acceptable, feasible, affordable, sustainable and safe, avoidance of all breastfeeding by HIV-infected mothers is recommended. Otherwise, exclusive breastfeeding is recommended during the first months of life” and should then be discontinued as soon as it is feasible.

•Exclusive BF first 6 months unless RF is acceptable, feasible, affordable, sustainable, safe (AFASS)•If RF, no BF•Revisit feeding at infant dx and/or 6 months; reassess at 6 months, if not AFASS, then BF/complementary foods; stop when nutritionally safe/adequate diet without BM is possible

Implementing AFASSDoherty AIDS 2007;21:1791-97

• Piped water, fuel, disclosure

• 311 met criteria – 20.5% chose BF

• 289 did not meet criteria – 67.4% chose FF

• Outcomes (Risk of HIV or death)– Met criteria, FF HR 1.0– Did not meet criteria, BF HR 3. 3– Did not meet criteria, FF HR 3. 6– Met criteria, BF HR 3.4

Case 6

• Healthy 2 week old born to HIV infected mother, when should he be tested? How?

a) ELISA at 6 months

b) HIV PCR assay at 6 weeks

c) Wait until 18 months

Algorithm for infant testing

CHER studyViolari, IAS 2007

• 6-12 week old infants, CD4 ≥25%

• Immediate or deferred (based on CD4/clinical – 20% > 1 yr, 25% < 1 yr)

• 377 enrolled– 96% survival immediate, 84% deferred

Case 7

• 33 year old woman who was diagnosed with HIV during previous pregnancy 2 years ago, received NVP for PMTCT. Can she receive NVP again?

SD-NVP and second pregnancyMartinson JAIDS 2007; McConnell JID 2007; Flys JID 2008

• West Africa and South Africa cohorts– ~ 2 years between pregnancies– Soweto (n=120) Pregnancy #1: 11.1%, #2: 11.2%– Abijan (n=41) Pregnancy #1: 13.2%, #2: 5.4%

• Uganda – ~32 months between deliveries– Retrospective (n=104) NVP-naïve: 16.7%, NVP-exposed: 11.3%– Prospective (n=103) NVP naïve: 18.7%, NVP-exposed: 20.5% – 6 week and 6 month prevalence similar between naïve and

exposed

Case 8

• 27 year old who received SD-NVP regimen 2 years ago, now has CD4 <250 and will start HAART. Should she start on NVP-containing HAART?

SD-NVP effect on HAART responseJourdain NEJM 2004Lockman NEJM 2007

Transition between PMTCT and careGinsburg AIDS 2007

• Mother-infant link– Maternal-child health cards

• Issues– immunizations– nutritional guidance, growth monitoring– contraception– infant HIV testing– maternal or infant HAART or OI prophylaxis

• MCH- HIV treatment clinic link– When to transition from MCH to HIV Care?– When to transition from HIV Care to MCH?

Thank you!Next session: October 9, 2008

Listserv: itechdistlearning@u.washington.eduEmail: DLinfo@u.washington.edu

Welcome to I-TECH HIV/AIDS Clinical Seminar Series

Next session: September 25, 2008

Grace John-Stewert, MD

PMTCT