Prevention of Perinatal HIV Transmission: The Role of

Epidemiology in Health Care Policy

Sindy M. Paul, M.D., M.P.H.

March 7, 2005

Epidemiology of HIV Disease in New Jersey: 12/31/04

• 5th in US Cumulative reported AIDS Cases

• Highest proportion of women (32%)

• 3rd US Cumulative reported pediatric AIDS cases

• 1,204/1,287 (94%) pediatric HIV/AIDS perinatal transmission

Timing of Perinatal HIV Transmission

• Cases documented intrauterine, intrapartum, and postpartum by breastfeeding*

In utero 25%–40% of cases Intrapartum 60%–75% of cases

Addition risk (14-29%) with breastfeeding

• Evidence suggests most transmission occurs during the intrapartum period

* Fowler, MG, Ped. Clinics of N. America 2000.

Prevention of Perinatal HIV Transmission

• The Risk Of Transmission Can Be Reduced

• Prenatal Care

• Mandatory Counseling/Voluntary Testing

• Know Serostatus As Early As Possible!

• Antiretroviral Therapy & OB Procedures

• PACTG 076: AZT Decreases Transmission From 25% to 8%

• Recommend Against Breast Feeding

Evaluation of Implementation

• Access to Prenatal Care

• Counseling and Testing: Provider & Patient

• AZT and other Antiretroviral Agent Use

• Impact on Transmission

• Missed Opportunities

• Potential Toxicities

• Potential Adverse Outcomes

Access to Prenatal Care 1993, 1995, 1996

• 25% of HIV Infected Pregnant Women Had No Known Prenatal Care

• In 2000: 14% No Known Prenatal Care & 6% 1-2 Prenatal Visits

• A Major Gap In Prevention Of Perinatal HIV Transmission In New Jersey

• An Opportunity For Intervention

Implementation Of Counseling And Testing Recommendations

• 1995: NJ Law Mandatory Counseling, Voluntary Testing

• Surveillance Data: 91% HIV Infected Pregnant Women Know Serostatus Prior to Delivery & 4% Tested at Delivery

• Statewide Assessment Diffusion of Counseling And Testing OBGYN

• Interview Study Of Pregnant Women

Provider Survey: Results

• 160/351 (51%) Completed Survey

• 94% Offer HIV Testing

• 90% Discuss Benefits of HIV Testing

• 77% Counsel

• 59% Offer All 3 Components

Respondents More Likely To Offer Counseling

• Fit Into Office Routine p<0.0001• Better Medical Outcome p=0.0261• Easy p=0.0016• Confident in Counseling p<0.0001• Patient Appreciation p=0.0001• Standard of Care p=0.0002• Actively Promoted p=0.0012• Discuss with Colleague p=0.0171

Conclusion

• Doing Well, but Room for Improvement

• Missed Opportunities

• Improved Diffusion and Implementation of HIV Counseling and Testing among OBGN Could be Accomplished through Peer Education

Interview Study: Pregnant Women

• Convenience sample - 170 Pregnant Women

• Objective: To Ascertain How Pregnant Women Perceive AZT as a Possible Option to Prevent Perinatal HIV Transmission by Examining Their Knowledge, Attitudes, Beliefs, and Intentions Surrounding AZT Use.

Demographic Profile

• African-American 53%

• Hispanic/Latina 29%

• Ages 18-34 84%

• Unemployed 63%

HIV Counseling and Testing History

• 74% Reported Being Told About Benefits of HIV Testing

• 90% Tested for HIV

• 10% Not Tested Yet

• 13/17 (76%) Intended to Be Tested

• 4/17 (24%) Did Not Intend to Be Tested

Intention to Use AZT

• 57% Would Use AZT

• 41% Unsure

• 2% Would Not Take AZT

Factors Associated With Intention To Use AZT

• Positive Beliefs About AZT p<0.0001• Recommended by Dr. or Nurse p=0.0023• Access to AZT at Clinic or Dr. p=0.0076• Enough Information p<0.0001

• Conspiracy Theories NOT ASSOCIATED

Conclusion

• Pregnant Women Are Willing to Consider AZT Use if They Are Given Adequate, Accurate Information.

Implementation of PHS Recommendations in New Jersey• ART use: increased from 8.3% in 1993 to

84.2% known in 2003

• Decrease in perinatal transmission from 21% in 1993 to 3.0% in 2003

• Room for improvement recent studies show vertical transmission can be as low as 1-2%

• What are the missed opportunities?

New JerseyPediatric HIV/AIDS Cases & Exposures

Born 1993-2004 By CategoryAs of December 31, 2004

Infected Indeterminate Seroreverter Total Reported

Birth Year

# % # % # %

1993 75 21 82 23 194 55 351

1994 55 17 103 32 162 51 317

1995 50 16 81 26 185 59 316

1996 39 13 76 26 180 61 295

1997 32 11 86 30 164 58 282

1998 23 7 94 31 191 62 308

1999 15 6 76 30 159 64 250

2000 13 5 73 27 182 68 268

2001 7 3 76 35 136 62 219

2002 4 2 78 36 134 62 216

2003 5 3 69 38 110 60 184

2004* 3 2 118 75 36 23 157

Total 326 12 1,012 31 1,833 58 3,163 1998

Missed Opportunities: Children Who Became Infected

• 7 children infected 1999, 1 infected 2000 (preliminary data reports through 12/31/00)

• 5 of the 8 (63%) no known or inadequate prenatal care

• 7/8 (88%) HIV status unknown to the delivery team

Missed Opportunities: Children Who Became Infected Continued• 1 of the 8 (13%) had prenatal care starting

in 3rd trimester with antiretroviral agents in pregnancy, labor/delivery, and neonatal period and a vaginal delivery

• Major gap: women presenting in labor with unknown HIV serostatus to the provider

• Contributing factor: lack of or inadequate prenatal care

Prevention of Perinatal HIV Transmission: ? Serostatus

• Rapid Test for Unknown Serostatus• Short Course Therapy Options: - 1

dose NVP labor onset & 1 dose NVP for the newborn at age 48 hours - ZDV+3TC in labor &1 week ZDV+3TC for the newborn -Intrapartum ZDV+6 weeks ZDV newborn -2 dose NVP regimen + 6 weeks ZDV

Hospital Survey:Management Labor Unknown Serostatus

• Questionnaire telephone survey of 12 hospitals Essex, Hudson, Union counties

• IRB approval

• 12 licensed acute care general hospitals

• 9/12 (75%) responded

• 6/9 (67%) provide obstetrical care

• 1/9 (10%) rapid test capability

Hospital Survey: Management Labor Unknown Serostatus

• 1/6 (17%) always offers CTS in labor

• 2/6 (33%) almost always offer CTS in labor

• 2/6 (33%) rarely or never offer CTS in labor

• 0 policy for rapid test/short course therapy

• 5/6 (83%) use standard EIA + Western Blot

• 1/6 (17%) use HIV DNA PCR

• Problem: obtaining results in 72 hrs to treat infant with ZDV

Plan of Action: A Statewide Policy for Unknown Serostatus

• Identify & involve providers & other stakeholders

• Education

• Development of a statewide policy for use by hospitals

• Dissemination of information

• Implementation of the policy

• Evaluation

Intent of the Standard of Care

• Provide HIV counseling and voluntary rapid or expedited testing of mothers or newborns if unknown HIV status or mother reports HIV infection with no documentation on the medical record

• Offer maternal &/or newborn ART if HIV +, mother reports being HIV +, or mother previously documented to be HIV +

Intent of the Standard of Care

• To decrease the risk of vertical transmission in every HIV exposed baby born in a New Jersey hospital to the best practice standards

Standard of Care:Women in Labor with ? HIV Status

• Provide counseling (pre- and posttest)

• Voluntary rapid or expedited HIV test

• If HIV positive provide preliminary lab results (CDC & ASTPHLD)

• If HIV positive offer short course therapy

• DO NOT DELAY RX pending confirmatory lab results

• Refer mother & child for follow-up care

Rapid Tests

• SUDS

• OraQuick

• Reveal

• Unigold

• Multispot

Rapid Tests: Oraquick

• Fingerstick, purple top tube, or OMT specimen• FDA approved 11/02 CLIA waived 1/03 except

OMT (FDA approved 3/04)• Not CLIA waived in NJ (lab regs)

- Need a lab licensed by NJDHSS to perform diagnostic immunology (HIV testing)

- Need to comply with CLIA ‘88 regs • ? Point of Service Testing

Rapid Tests: Reveal

• FDA approved 4/17/03

• Not CLIA waived

• Moderate complexity test

• Most be done in licensed lab

• Batched - minimum 8 specimens/batch

Rapid Tests: Unigold

• FDA approved 12/03

• Whole blood, serum, plasma

• CLIA waived

• 10 minutes

Multispot HIV1/HIV2 Test

• FDA approved

• Moderately complex

• Not CLIA waived

• Fresh or frozen plasma

• 10 minutes

How do other Rapid Tests Perform Compared to SUDS?

False False Negative Sensitivity Positive Specificity

Determine 0/37 100% 2/1649 99.9%Reveal 5/67 93.1% 16/1581 99.0%

MultiSpot 0/45 100% 0/769 100%OraQuick 0/73 100% 2/1639 99.9%

OraQuick Oral 0/72 100% 18/1569 98.9%Unigold 4/45 91.1% 2/915 99.8%SUDS 1/72 98.6% 6/1641 99.6%

1649 Clients at Testing Site / STD Clinics

Current Clinical Response to Rapid Testing Preliminary

Positive Results• Occupational Exposure

• Women in labor with unknown HV status

• Why? Because tested person benefits

- PEP reduces risk of occupational transmission

- Short course therapy reduces risk of mother-to-child HIV transmission

Clinical Trial Data Supporting Short Course Therapy

• International studies show not as effective as PACTG 076 regimen (66% decrease)

• Thailand Study Short Course AZT

- Non-breastfeeding population

- From 36 weeks through labor

- Did not include infant prophylaxis

- 50% decrease transmission (9.4% AZT vs 18.9% placebo)

Clinical Trial Data Supporting Short Course Therapy - Petra

• Petra Study (Uganda, S. Africa, Tan.)

- Breastfeeding population

- Oral AZT/3TC from 36 weeks and during labor& delivery

- Oral AZT/3TC to woman and infant q 12 hours for 7 days postpartum

- Reduced transmission by 38% (10% AZT/3TC vs. 17% placebo)

Clinical Trial Data Short Course Therapy HIVNet 012 Uganda

• Breastfeeding population• Intrapartum/postpartum/neonatal NVP vs.

short course neonatal AZT• 200 mg po NVP at labor onset; 2mg po NVP

to infant within 3 days• 600 mg AZT labor onset; 300 mg AZT q 3 hr

in labor; 4mg/kg AZT infant bid 7 d

- Transmission rate 12% NVP vs. 21% AZT

Goals of Treatment of HIV Infected Pregnant Women

• Treatment of mother’s HIV disease

• Reducing the risk of vertical HIV transmission

• Health of the mother and the child

CDC: What if a Woman Presents in Labor with Unknown Status?

• Counseling – Opt out option possible (check state regs)

– CDC Mother-Infant Rapid Intervention at Delivery (MIRIAD) counseling feasible in labor

• Template developed based on NJ

• Counselors should be trained

CDC Recommendations for Women in Labor with ? HIV

• Rapid testing

– POCT shorter turn around time

• Short course therapy

• Referral for care and treatment

CDC: Eligibility for Counseling & Offering Rapid Testing in Labor

• Undocumented HIV status

• Addition re-screen continued risk – Approach similar to syphilis retesting in

3rd trimester and at delivery for high risk– H/O STD, sex for $ or drugs, multiple sex

partners during pregnancy, illicit drug use, HIV + or high risk partner, signs and symptoms of seroconversion

Concerns with Counseling Women in Labor

• How to present HIV counseling and offer testing during labor?

• Development of model counseling session

- Review of Lit & Discussion with CDC – Meetings teaching & non-teaching hospital staff– Focus group postpartum women

• Statewide TOT with MCH consortia

Counseling During Labor

• Not a great time, but possible!• Policy and procedure in place with a

counseling “script”• Materials for patient education/informed

consent• Culturally and linguistically appropriate• Done for other OB procedures i.e. C-section

Formula for HIV Counseling and Testing in Labor: C3R3

• C3

• Confidentiality• Comfort• Consent

• R3

• Reasons to Test

• Results

• Rx to decrease risk

Confidentiality

• Who is in the room with the patient?

• How can you assure confidentiality during

- History taking

- Giving test results

- Giving medication for treatment

• Be creative - counseling part of admission process, visitors get coffee, in bathroom

Comfort

• What is her level of discomfort/anxiety?• How is her pain being managed?• Tell the woman she should signal you when a

contraction is happening, so you can pause until it is over.

• Important to show empathy:body language &/or touch.

• Pause to verify understanding.

How Much Information is “Informed” Consent?

• HIV is the virus that causes AIDS• A woman can be at risk and not know it• Effective intervention can prevent

transmission to the baby and improve mother’s health

• Testing recommended all pregnant women • Women who decline testing won’t be denied

care

Reasons for HIV Testing During Labor

• HIV the virus that causes AIDS is spread by unprotected sexual intercourse

• Therefore, all pregnant women may be at risk for HIV infection

• Pregnant woman has a 1 in 4 chance of passing HIV to baby if she is not treated

• ART in labor/delivery & neonatal period: 1 in 10 babies will get infected

Giving the Results: Preliminary Positive Results

• May be infected with HIV

• Confirm with a 2nd test (no test =perfect)

• May be best to start ART for you & baby

• Wait for confirmatory results before breastfeeding (Can start only if neg.)

• If confirmatory test neg. stop medication

• If confirmatory test + cont. meds, referral for care, follow-up testing baby

Giving the Results: Preliminary Negative Results

• Not infected with HIV

• Emphasize risk reduction plan to prevent transmission

• Referral for intensive counseling if high risk

• Note: a negative rapid test is negative and does not need confirmation that it is negative

RX: Treatment to Reduce Perinatal Transmission

• ART in labor/delivery and to the baby after birth decreases risk of transmission to 1 in 10

• National guidelines: 4 RX options

• Referral of mother and child to provider with experience and expertise RX HIV

• Let pediatric provider know the child is HIV exposed (NJ has a law for this)

Other Potential Barriers and How to Overcome Them: Lab

• Cost: NJ law - mandatory counseling & voluntary testing substituting 1 test for another

• Volume of testing required: - unknown serostatus not all 120,000 - Estimated 1,100-1,200 women (1% based on electronic birth certificate data) women with no prenatal care annually statewide

Potential Lab Barriers - Continued

• Releasing preliminary positive lab results

- Recommended by CDC & ASTPHLD

- Lab alert

- CME article in NJ Medicine, AIDSLine

• PPV for SUDS

- Better tests now available & on the horizon

Dissemination of the Standard of Care

• Development & dissemination of a template counseling session for pregnant women

• Hospital mailing with a Laboratory Alert

• Continuing education programs

• Web-based CME www.acadmed.org

• Hospital TA

• Articles for Publication: medical & lab

Dissemination - Continued

• Collaboration with NJDHSS hospital licensure staff

• Collaboration with the Board of Medical Examiners

- License physicians and nurse midwives

• Collaboration with OB Society & ACOG

Evaluation of Implementation & Effectiveness

• Repeat questionnaire survey

• Surveillance data for women presenting with unknown serostatus - # positive rapid tests - # short course therapy - # children who serorevert - # children infected

• Retrospective medical record review

How are we Doing? Repeat Hospital Survey Spring 2003

• 24/59 (41%) OB hospitals responded

• 23/24 (96%) aware standard of care

• 19/23 (83%) always or almost always offer counseling in labor

• 19/22 (86%) offer testing in labor

• 16/24 (67%) rapid or expedited testing

• 4/4 (100%) without rapid testing plan within 6 months

How are we Doing? Repeat Hospital Survey Spring 2003

• 17/19 (89%) offer short course therapy if rapid or expedited HIV test during labor is a preliminary HIV positive result

Summary of Recent Perinatal Infections: 2003-2004

• 7 cases • Only 1 received appropriate care and

prevention medications• 2 Mom tested after birth

– 2 No PNC, no meds– 1 neonate start ZDV day 3– 1 neonate no ZDV– 2 c/s (1 non-elective, 1 unknown)

Summary of Recent Perinatal Infections: 2003-2004:

Continued• 3 Mom diagnosed before pregnancy

- 3 No PNC, no meds

- 1 neonate no ZDV, 1 unknown, 1 ZDV

- 2 vaginal deliveries (1 home delivery)

- 1 c/s 34 weeks type unknown • 1 Mom diagnosed before pregnancy

- PNC starting 7 months, non-adherent meds

-elective c/s 38 weeks, ZDV L&D, neonate day1

Efforts to Decrease Missed Opportunities

• Target Population

- Women in labor with ? HIV status

- Women not in PNC• Approach:

- Provider education

- Outreach to women

- Information on barriers – repeat hospital survey

- Missed opportunities work group

Free HIV Test And Care During Pregnancy.

Call The NJ AIDS Hotline 1-800-624-2377.YOU CAN HELP Prevent HIV In Your Baby.

Pregnant.Are You HIV+?Find Out.

Potential Adverse Outcomes

• Birth Defects - Match HARS To Birth Defects Registry - No Evidence Of Increased Incidence

• Cancer -Match HARS To Cancer Registry -No Evidence Of Increased Incidence

• Current Studies: Population-Based Approach Through Registry Matching

Potential Toxicities: Mitochondrial Disease

• Primate Studies

• French Cohort - 8/3,000 Children

• US, Europe, Thailand, Africa - 0/27,000 Children

• Current Studies in New Jersey - None Detected

Controversies In Reducing Perinatal HIV Transmission

• Mandatory Counseling, Voluntary Testing - New Jersey Law

• Mandatory Testing of Pregnant Women

• Mandatory Testing of Newborns - Currently required in New York - Ryan White Legislation 2000 - Representative Coburn Letter

Controversies In Reducing Perinatal HIV Transmission

• Universal Screening With Opt Out Option - IOM Report & Supported by ACOG

• CDC Revised Recommendation - HIV screening = routine part prenatal care - Provide info e.g. brochure, pamphlet, video before testing - Written or verbal consent- opt out for women in labor

Summary

• Epidemiology used to develop policy• Perinatal HIV transmission decreased from

21% to 3% • Continue to use epidemiology to evaluate

the implementation and effectiveness of recommendations

• Trying to achieve maximal reduction of perinatal HIV transmission