Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug-Use or Other Nonoccupational exposure to HIV Gonzalo Bearman MD, MPH Assistant Professor of Internal Medicine and Public Health Divisions of Quality Health Care & Infectious Diseases Associate Hospital Epidemiologist VCU Health System

Outline Definition of nonoccupational exposure to HIV What is the estimated risk based on the exposure type? What is the HIV status of the source and exposed patient? –Signs and symptoms of acute retroviral syndrome –Rapid HIV testing Data supporting the uses on nPEP for HIV CDC nPEP protocol algorithm Antiretrovirals of choice –Side effects –Maximizing adherence –Special considerations Follow-up of the patient Expected impact of the nPEP Conclusion

Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States Recommendations from the U.S. Department of Health and Human Services MMWR January 21, 2005 / 54(RR02);1-20

nPEP is Not Intended for: “Persons who engage in behaviors that result in frequent, recurrent exposures that would require sequential or near- continuous courses of antiretroviral medications (e.g., discordant sex partners who rarely use condoms or injection-drug users who often share injection equipment) should not take nPEP.” MMWR January 21, 2005 / 54(RR02);1-20

DHHS Recommendations for nPEP DHHS recommends the prompt initiation of nPEP with HAART when persons seek care within 72 hours after exposure, the source is known to be HIV infected, and the exposure event presents a substantial risk for transmission. When the HIV status of the source is not known and the patient seeks care within 72 hours after exposure, DHHS does not recommend for or against nPEP but encourages clinicians and patients to weigh the risks and benefits on a case- by-case basis. MMWR January 21, 2005 / 54(RR02);1-20

What Constitutes a Nonoccupational Exposure to HIV? Has exposure of vagina, rectum, eye, mouth, non-intact skin, or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or any visibly bloody body fluid occurred? MMWR January 21, 2005 / 54(RR02);1-20

What is the Estimated Risk? MMWR January 21, 2005 / 54(RR02);1-20

Efficacy of nPEP Current studies suggest that nPEP might reduce the risk of infection with HIV after sexual exposures –However: participants were not randomly assigned and sample sizes were too small for statistically significant conclusions. For ethical and logistical reasons, a randomized, placebo-controlled clinical trial of nPEP probably will never be completed. –High quality data may never be available for NPEP MMWR January 21, 2005 / 54(RR02);1-20

Observational Study Data-nPEP High-risk HIV incidence cohort in Brazil, nPEP –4-day starter packs of zidovudine/lamivudine were administered to 200 homosexual and bisexual men. In men taking nPEP after a self-identified high-risk exposure –Seroincidence was 0.7 per 100 person-years (one seroconversion) among men who took nPEP and 4.1 per 100 person-years among men who did not take nPEP (11 seroconversions) Harrison LH, Do Lago RF, Moreira RI, Schechter M. Demand for post-sexual-exposure chemoprophylaxis for the prevention of HIV infection in Brazil [abstract 492]. Presented at the 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, California, January 30--February 2, 2000.

Observational Study Data Ffficacy of postexposure prophylaxis is a case-control study of needlestick injuries to health-care workers. –The prompt initiation of zidovudine was associated with an 81% decrease in the risk for acquiring HIV. N Engl J Med 1997;337:

MMWR January 21, 2005 / 54(RR02);1-20

HIV Status of the Potentially Exposed Person? Baseline HIV testing should be performed on all persons seeking evaluation for potential nonoccupational HIV exposure. – FDA-approved rapid test kit If rapid tests are not available: – Assume that the potentially exposed patient is not infected MMWR January 21, 2005 / 54(RR02);1-20

HIV Status of the Source? If the HIV status of the source is unknown, it should be determined whether the source is available for interview and HIV testing. –Risk factors for HIV infection; signs and symptoms of acute retroviral syndrome. If the risk associated with the exposure is considered substantial –nPEP can be started pending HIV testing of the source and then stopped if the source is determined to be noninfected. MMWR January 21, 2005 / 54(RR02);1-20

Acute Retroviral Syndrome Common signs and symptoms of acute retroviral syndrome (occurring in >50% of patients): fever adenopathy pharyngitis rash myalgias arthralgia less common: diarrhea, headache, nausea, weight loss, thrush

MMWR January 21, 2005 / 54(RR02);1-20

Reveal:Rapid HIV Test MedMira Laboratories Rapid HIV test performed on patient serum –HIV antibody test SENSITIVITY: 99.8% –All positive tests are confirmed by western blot Processing time for the test (upon receipt by the laboratory) is about minutes. –It is critical that the the source blood be drawn immediately and delivered to the laboratory in an expeditious manner

 PEP not indicated.  Refer to follow-up clinic for hepatitis B & C testing Has exposure of vagina, rectum, eye, mouth, non-intact skin, or percutaneous contact with blood, semen, vaginal secretions, rectal secretions, breast milk, or any visibly bloody body fluid occurred? Is the source patient HIV+ or at high risk of HIV infection?  Send rapid HIV serum test on source patient (2 serum separator tubes) to Microbiology Lab. Is the source patient HIV infected by rapid testing? Does source patient have signs/ symptoms of acute retroviral syndrome?*  Begin Combivir® 1 tablet twice daily + Kaletra® 3 capsules twice daily o Obtain 1st day doses from Blue ED Omnicell; complete pre-printed prescriptions & place in Omnicell return bin o Write Rx for 10 day supply of drugs (reduced pricing available in AD Williams Pharmacy).  Check AST, ALT, BUN, creatinine, CBC/diff, pregnancy test (if tests abnormal, page ID fellow) Follow-up clinic for hepatitis B & C follow-up. Is the source patient present? Yes No YesNoYes No YesNo Did exposure occur <72 hours ago? Yes VCU nPEP Protocol

MMWR January 21, 2005 / 54(RR02);1-20 Preferred Antiretroviral Therapy A 28-day course of HAART is recommended for persons who have had nonoccupational exposure to blood, genital secretions, or other potentially infected body fluids of a persons known to be HIV infected when that exposure represents a substantial risk for HIV transmission

Maximizing Adherence nPEP Decrease Pill burden: –prescribing medications with fewer doses and fewer pills per dose Educate patients about the importance of adherence and about potential side effects Offer ancillary medications for side effects (e.g., anti-emetics and anti-diarrheals) Provide ongoing encouragement and consultation by phone or office visit MMWR January 21, 2005 / 54(RR02);1-20

Adverse Effects of PEP Adverse effects of combivir + kaletra: diarrhea, nausea, vomiting, headache, insomnia, myopathy,  transaminases, pancreatitis, anemia, neutropenia

Special Considerations When the source-person is available for interview: –His or her history of antiretroviral medication use and most recent viral load measurement should be considered when selecting antiretroviral medications for nPEP. This may help avoid prescribing antiretroviral medications to which the source-virus is likely to be resistant. MMWR January 21, 2005 / 54(RR02);1-20

Follow-up Testing and Care Test the exposed patient to HIV antibodies at baseline and at 4--6 weeks, 3 months, and 6 months after exposure to determine whether HIV infection has occurred. Testing for sexually transmitted diseases: –hepatitis B and C Pregnancy testing should be offered Follow patient for signs of acute-retroviral seroconversion syndrome MMWR January 21, 2005 / 54(RR02);1-20

What is the Expected Public Health Impact of this New Guideline? Although 40,000 new HIV infections occur in the United States each year, the impact on nPEP may be limited –Few exposed persons seek care after nonoccupational exposure –Many people have frequently recurring exposures and would not benefit from nPEP. –Clinicians and exposed patients are unaware of the availability of nPEP –Financial means of paying for nPEP might limit it’s use 28 days of Combivir/Kaletra - $1200 MMWR January 21, 2005 / 54(RR02);1-20

Conclusion DHHS recommends nPEP with HAART when persons seek care within 72 hours after exposure, the source is known to be HIV infected, and the exposure event presents a substantial risk for transmission. If the HIV status of the source is not known and the patient seeks care within 72 hours after exposure, DHHS does not recommend for or against nPEP but encourages clinicians and patients to weigh the risks and benefits on a case-by- case basis. The prompt initiation of HAART (within 72 hours) following substantial nonoccupational HIV exposure and it’s continuation for 28 days may reduce the likelihood of transmission.