Non-Occupational PEP: Key Issues as of September 2003

1. Non-Occupational PEP:Key Issues as of September 2003 Michelle Roland, MD Assistant Professor of Medicine USCF Positive Health Program/ San Francisco General Hospital

2. A Healthcare Provider Seeks Advice • Her HIV positive clinic patient called at 8 this morning. He is in a panic. • The condom broke while he was having sex with his HIV negative partner this morning. • He asks if there is anything they can do to reduce the chance that his partner will become infected. Is there anything that will help?

3. Current Guidelines • PEP for consensual sexual exposures • 1998 US Guidelines neither recommend nor discourage but are under revision following May 2001 consultation • State of MA recommends and supports; Rhode Island recommends • Recommended in France, Italy, Spain, Switzerland, Australia • PEP following sexual assault • Guidelines in NY and CA, France

4. Questions to Guide Decision: If and How to Provide PEP • Timing: </> 72 hours; facilitating rapid access • Is this a risky exposure? • Specific sexual activity: per contact risk of transmission • Partner’s HIV status: local HIV demographics if ? • Partner’s antiretroviral and HIV RNA history: modifying the PEP regimen • Exposed persons last negative HIV test and interval exposures: how likely are they to be HIV negative now? • Risk behavior pattern and referral needs

5. Why Consider Non-Occupational PEP? 1. Occupational PEP • AZT reduces risk by 81% 2. Mother to child transmission • reductions seen even in cases where AZT initiated post-partum (9.2 vs 26.6%); recent SA data supports 3. Animal models • protection in oral and vaginal mucosa models • timing (24 better than 48- 72 hours) and duration of therapy (28 days) are important 4. Observational studies

6. Is Non-Occupational PEP Effective? There are no efficacy data in this setting • ethical concerns re control groups • feasibility limitations given low per contact transmission

7. Risk of Specific Exposures Per Contact Transmission Rate • Receptive Anal 0.8 - 5% • Insertive Anal < 0.1 - 1% • Receptive Vaginal < 0.1 - 1% • Insertive Vaginal 0.01 - 5.6% • Shared Needles 0.67% • Occupational NS 0.3% • Receptive Oral ???

8. Observational Data - Brazil Study • 202 MSM given access to PEP: 1998 - 2001 • Baseline sero-incidence 3.4% • Provided 4 day supply of combivir • Instructed to take within 48 hours of: • receptive or insertive anal intercourse • insertive vaginal intercourse • receptive oral intercourse with ejaculation • Report 24.2 month median follow-up M. Schechter, et al, 9th CROI Feb, 2002

9. Results • PEP initiated 110 times in 73 people • 92% eligible exposures and 92% completed 28 days HIV Seroconversions: • 1/66 used PEP: 0.6%/100 person years • 10/131 no PEP: 4.2%/100 person years

10. Limitations Was NOT designed as an efficacy study Did not report on risk behavior differences between the 2 groups (no PEP group could have been riskier, thus more likely to seroconvert)

11. San Francisco Seroconversion Data • PEP 1: No infections in 401 potentially exposed individuals at 6 months • 4 infections at 12 months due to on-going exposure • PEP 2: started with…1 infection with late initiation of PEP • Started PEP medication at 72.5 hours • Missed some doses in first few days of one nucleoside • Highly ARV exposed source with unknown resistance (none upon later testing)

12. Evaluation of Seroconversion in PEP 1 and PEP 2 • Study #1 (1997 – 1999): subjects were provided antiretroviral medication (ARV) and 5 sessions of risk reduction counseling • Study #2 (2001 – present): subjects received ARV and were randomized to 2 versus 5 risk reduction counseling sessions

13. Early Seroconversion Following PEP Data pending publication

14. SF Overview 1) PEP 1: Feasibility Study • October 1997 - April 1999 2) Clinical PEP Services • April 1999 - April 2001 3) PEP 2: Randomized Counseling Intervention • April 2001 – November 2002 4) PEP Following Sexual Assault 5) CDC PEP Registry

15. SF Feasibility Study: Objectives To describe the: 1. Demographic and behavioral characteristics of individuals who seek PEP after sexual or drug use exposures to HIV 2. Adherence and toxicity associated with 28 days of PEP medications

16. Exposure Characteristics Unprotected: Receptive or insertive anal intercourse Receptive or insertive vaginal intercourse Receptive oral sex with ejaculation Shared injection drug equipment Source Characteristics Known HIV positive MSM Past or present IDU Commercial sex worker Anonymous Index Subject Inclusion Criteria AND

17. Interventions 1) ARV Medications • Usually 2 nucleosides • Source HIV status/med hx unknown: Combivir • Known: adjust to minimize resistance • Consider 3rd drug if detectable HIV on meds 2) Adherence Counseling 3) Risk Reduction Counseling - 5 sessions

18. Important Findings • Timing: Meds initiated late (33 hours) • Indications: PEP requested for high risk exposures (52% RA vs 5% oral; 50% partners HIV+) • Toxicity: Subjective side effects but no lab toxicity • Adherence: 28 days good (> 78%), + missed doses • Source ARV resistance: common and increasing • Risk behavior: reduced at 6 and 12 months • STDs: no increase in year following PEP

19. Clinical PEP Services: Key Implementation Issues • Referrals: phone and walk-in • Eligibility criteria • Medical evaluation and follow-up • Medication regimens • Lab monitoring • Record keeping and HIV Ab testing follow-up • Counseling and referral options

20. PEP 2 Randomized Counseling Intervention • 2 vs 5 sessions of risk reduction counseling • clinician vs counselor adherence counseling

21. A Lesson Learned… Viral Load Testing

22. HIV RNA as a Diagnostic Tool • HIV testing prior to PEP provides the opportunity to minimize toxicity, cost, and the development of drug resistance • While HIV antibody tests will detect the majority of HIV-infected individuals, their inability to detect infection in the pre-seroconversion window period has generated interest in using the more sensitive HIV RNA-based assays in the setting of PEP

23. …Not a Good Idea • Our study demonstrates that the positive predictive value in HIV RNA assays (using the lower limit of detection as the cutoff for true positivity) among individuals presenting for PEP is unacceptably low for bDNA-based testing and possibly acceptable for PCR-based testing in this context. • Data pending publication

24. What do we know aboutPEP following sexual assault?

25. North America and Europe

26. PEP and Sexual Assault • Uptake low in low prevalence areas • International implications: high prevalence areas • Challenges: how do you counsel, test, provide informed consent in this context? • Who should get PEP and is this different depending on local prevalence?

27. California State Guidelines: Risk Stratification for PEP For South Africa, assume perpetrator is HIV+

28. There is Demand for PEP PEP2 Study Telephone Line Experience

29. The study was advertised as follows: • Community newspapers • Billboard in the Castro district • Palm cards and posters distributed in bars, sex clubs, gyms and at events in the gay community • A website; appropriate links were aggressively pursued • Internet marketing on sites geared towards individuals seeking sex partners with advertisements and daily postings • Outreach to HIV prevention service organizations, primary medical care providers, Emergency Departments and hotlines.

31. Availability of PEP Study Staff Telephone inquiries were returned 8 AM - 10 PM, seven days a week, including weekends and holidays. A physician was available to call prescriptions to local pharmacies prior to enrollment.

32. Number/Type of Calls • 968 calls were recorded between 4/01 and 7/31/02 • 60/month • 28% occurred during non-business hours • 719 (74%) seeking study services • 249 (26%) from out of the area or requesting other information.

33. Callers Male = 94% Median age = 33 (16 - 74) yrs 90% had an exposure that qualified them for the study 38% of exposed callers reported exposures with a source who was known to be HIV+ 60% of sources were at high risk of HIV infection

34. PEP Eligibility 87% were eligible for the study • Of these eligible callers: • 73% elected to participate in the study • 16% were referred off-study (to the city STD clinic, primary care provider, other provider) • 11% declined PEP

35. Who Declined PEP • < 21 yo (OR = 6.0, p < 0.001), female (OR = 2.9, p = 0.046) and exposed to partners of unknown HIV status (OR = 1.9, p = 0.035) • 13% did not come to the study site; female gender was the only association (OR = 4.1, p=0.007).

36. Prescribing by Phone 75% received a telephone prescription prior to enrollment in the study, including individuals seeking care outside of the study Source partner information was used in 18% of telephone evaluations to determine the PEP regimen

37. Advice Calls Among the 249 individuals calling for advice: • 38% involved exposures in individuals from out of the geographic area • 13% were from health care providers seeking advice • Calls were received from 21 states, Canada, the UK and Hong Kong.