1. Toward Elimination of Perinatal HIV Transmission in the U.S. Margaret A. Lampe, RN, MPH Division of HIV/AIDS Prevention Centers for Disease Control & Prevention Ryan White CARE Act Grantee Meeting August 30, 2006 The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of CDC.

2. Number of cases 0 200 400 600 800 1000 Number of cases 19861985198719881989199019911992199419931995199619971998199920002001200220032004 Estimated Number of Perinatally Acquired AIDS Cases, by Year of Diagnosis, 1985-2004 – United States PACTG 076 & USPHS ZDV Recs ~95% reduction CDC HIV screening Recs Year of Diagnosis

3. Background Rates of perinatal HIV Transmission of < 2% are possible with: 1. Early identification of maternal HIV infection 2. 3 part (antenatal, peripartum and neonatal) antiretroviral regimen 3. Pre-labor cesarean section if a maternal viral load of <1000 copies/ml is not achieved Approximately 144-236 infants acquired HIV infection via MTCT in the U.S. in 2002 MMWR: June 2, 2006 / 55(21);592-597 In 2000, ~40% of HIV-infected infants’ mothers not tested until birth or later

4. Perinatal HIV Testing Balance Shifting Benefits versus risks of testing pregnant women for HIV have shifted over years BENEFITSRISKS

5. CDC/USPHS Guidelines for Perinatal Testing in the U.S. First edition, 1985 No treatment Growing stigma Second edition, 1995 AZT prophylaxis reduces MTCT universal counseling/voluntary testing Marked decline in perinatal cases Third edition, 2001 Maternal treatment advances allows both mothers and babies to benefit “HIV screening should be a routine part of prenatal care for all women.” Repeat testing 3 rd trimester women at risk and in high prevalence areas Consider rapid HIV testing for women in labor with unknown HIV status BENEFITS RISKS BENEFITS RISKS BENEFITS RISKS

6. Implementation of recommended prenatal screening tests, 1998/1999 TestFrequency (%) (n=5,144) Hepatitis B96.5 Syphilis98.2 Rubella97.3 HIV57.2

7. Canadian Results, 1999-2001 ProvincePolicyN%Tested AlbertaOpt-out37,96398 New &LabOpt-out4,77094 QuebecOpt-in73,78183 B ColumbiaOpt-in41,73980 OntarioOpt-in129,75854

8. “Dear Colleague” Recommendations April 22, 2003 No child should be born in the U.S. whose HIV status (or mother’s status) is unknown Routine, opt-out screen prenatally Rapid, opt-out test at labor and delivery for women with no prenatal test result in the medical record Newborn testing

9. Advancing HIV Prevention Strategy 4: Further Decrease Perinatal HIV Transmission April, 2003 Work with partners to promote routine, voluntary prenatal testing, with the option to decline Develop guidance for using rapid tests during labor and delivery or postpartum Develop guidance for routine screening of infants whose mother was not screened Monitor integration of routine prenatal testing into medical practice Case control study to assess reasons why perinatal HIV infections occurring

10. Rapid HIV Testing in L&D: An important safety net Even when begun in labor, ARV prophylaxis can reduce MTCT by up to 50% (rates of ~25% without interventions, & 9-13% with ARVs). “good”-performing rapid HIV tests are now available in the U.S. L&D Rapid testing has been shown to be both acceptable & feasible, with some logistical challenges (MIRIAD study- JAMA, July, 2004)

11. The rapid test is done on this counter, extra supplies are stored below. OB physicians and midwives share MIRIAD testing L&D Point-of-Care Testing Station

12. Turnaround Times for Rapid Test Results, Point-of-Care vs Lab Testing Point-of-care testing: median 45 min (range 30 min – 2.5 hours) Same test in Laboratory: median 3.5 hours (range 94 min – 16 hours) MMWR 52:36, Sept 16, 2003

13. Impact of Advancing HIV Prevention on Perinatal Activities Changes in state legislation on perinatal HIV testing (work with ACOG) All states being asked to provide estimate of prenatal HIV testing rates to CDC Perinatal screening chart reviews underway in 16 states

14. Continued Efforts in Perinatal HIV Prevention Continue to: o Work with states to promote universal prenatal HIV testing and to streamline testing procedures o Develop methods for the ongoing estimation and feedback on recommended perinatal screening tests o Support & monitor implementation of rapid HIV screening for women in labor with undocumented prenatal HIV status

15. Four FDA-approved Rapid HIV Tests Sensitivity (95% C.I.) Specificity (95% C.I.) OraQuick Advance - whole blood - oral fluid - plasma 99.6 (98.5 - 99.9) 99.3 (98.4 - 99.7) 99.6 (98.5 - 99.9) 100 (99.7-100) 99.8 (99.6 – 99.9) 99.9 (99.6 – 99.9) Uni-Gold Recombigen - whole blood - serum/plasma 100 (99.5 – 100) 99.7 (99.0 – 100) 99.8 (99.3 – 100)

16. Four FDA-approved Rapid HIV Tests Sensitivity (95% C.I.) Specificity (95% C.I.) Reveal G2 - serum - plasma 99.8 (99.2 – 100) 99.8 (99.0 – 100) 99.1 (98.8 – 99.4) 98.6 (98.4 – 98.8) Multispot - serum/plasma - HIV-2 100 (99.9 – 100) 100 (99.7 – 100) 99.9 (99.8 – 100)

17. Positive Predictive Value of a Single Test Depends on Specificity & Varies with Prevalence Test Specificity HIV Prevalence Predictive Value, Positive Test 10% 99% 98% 92% 5% 98% 96% 85% 2% 95% 91% 69% 1% 91% 83% 53% 0.5% 83% 71%36% 0.3% 75%60% 25% 0.1% 50% 33% 10% OraQuickSingle EIAReveal 99.9%99.8%99.1% 97% 95% 87% 77% 63% 50% 25% Uni-Gold 99.7% In practice, the specificity and actual PPV may differ from these estimates. Trade names are for identification only and do NOT imply HHS or CDC endorsement

18. Prevalence of Diseases Screened for in Newborns Tyrosinemia: 1 in >300,000 Maple-syrup urine disease: 1 in 175,000 Homocystinuria: 1 in 100,000 Galactosemia: 1 in 60,000 Phenylketonuria: 1 in 14,000 Hypothyroidism: 1 in 4,000 Perinatal HIV exposure, US1 in 670 Perinatal HIV infection, US1 in 2,680 to 1 in 33,500 (according to interventions)

19. Positive Predictive Value: Newborn Screening SpecificityPPV PKU99.72.65% Galactosemia99.70.57% Hypothyroidism98.31.77% Adrenal Hyperplasia 99.00.53% Newborn Screening results, 1993 Arch Pediatr Adolesc Med, July 2000

20. OIG Report: Reducing Obstetrician Barriers to HIV Testing (2002) “CDC should facilitate the development and states’ implementation of protocols for HIV testing during labor and delivery in order to promote testing in this setting as the standard of care.”

21. Perinatal HIV Rapid Testing Protocol Team Convened by CDC Obstetrics Pediatrics Nursing Public health practice Health education and training Blood screening Laboratory science Epidemiology Rapid HIV testing technology Care and support of HIV- infected pregnant women 10 individuals with expertise in:

22. Rapid HIV-1 Antibody Testing During Labor & Delivery for Women of Unknown HIV Status A Practical Guide and Model Protocol January 30, 2004

23. Purpose of Model Protocol Practical guidance to: Clinicians Laboratorians Hospital Administrators Public Health Professionals Policy Makers Provide general structure of a rapid HIV testing protocol, can be adapted locally

24. Contents Overview: Planning—considerations for getting started Choosing type of test Location (L&D or Lab) Training Key elements of a local protocol Eligibility Opt-out approach Interpreting preliminary and confirmatory results Providing positive and negative results Intrapartum clinical care Follow up of HIV + women and exposed neonates HIV Reporting

25. Contents Overview: Management Considerations Key players & stakeholders Ensuring proficiency & competency References & Resources Appendixes Dear Colleague Letter Provider guides for opt-out and opt-in (sample consent form) Provider Formula: “C 3 R 3 ” Confidentiality, Comfort, Consent Reason, Results, Rx Boxed Case Studies

26. CDC Recommendation “Hospitals should adopt a policy of routine, rapid HIV testing using an opt-out approach for women who have undocumented HIV test results when presenting to labor & delivery.”

27. National Implementation Plan Rapid Testing in L&D 1. Promote with key partners 2. Train & build capacity 3. Monitor & evaluate 4. Technical Assistance

28. Regional Strategic Planning Workshops FXBC- strategic planning with invited hospital teams of leaders Plenary presentations from CDC with the evidence and making the case. Lessons from the field. Facilitated SWOT Analysis Facilitated Action Plan Follow-up technical assistance Fed well

29. “Revised Recommendations for… Adults Adolescents and Pregnant Women in Health Care Settings”. PROPOSED Updates for Pregnant Women, Fall 2006 Universal opt-out HIV screening Include HIV in panel of prenatal screening tests Consent for prenatal care includes HIV testing Notification and option to decline Second test in 3 rd trimester for pregnant women: Known to be at risk for HIV In key jurisdictions In high HIV prevalence health care facilities Opt-out rapid testing for women with undocumented HIV status in L&D Initiate ARV prophylaxis on basis of rapid test result Newborn testing if mother’s status unknown

30. Conclusion Until all pregnant women with HIV access screening prenatally, the promise of ACTG 076 and other clinical trials cannot be realized. Rapid testing provides a last opportunity to reduce the impact of missed prevention opportunities

31. CDC Resources on the Web http://www.cdc.gov/hiv/projects/perinatal/ Opt-out prenatal testing Rapid testing at labor and delivery Advancing HIV Prevention initiative Perinatal HIV Prevention grantees