Post-Exposure Prophylaxis Review for International Visitors

Transcription

1 Post-Exposure Prophylaxis Review for International Visitors

2 Case Presentation 27 yo nurse presents to Urgent Care for a needlestick 2 days ago from a diabetic lancet. Source patient (SP): 35 yo male known HIV+ (wasn t known at the time) Would you offer her PEP? If so, which agents? What more would you like to know?

3 Case Presentation continued What is her risk for contracting HIV? Are there factors that might affect this risk? How effective is PEP? Is it too late to start PEP? What are the drawbacks of starting PEP? Which regimen(s) should be considered? What follow-up should be arranged?

4

5 Risk Factors for Seroconversion after Needlesticks CDC-sponsored case-control study 33 cases, 665 controls s/p needlestick from confirmed HIV+ SPs AZT only for PEP

6 Risk Factors for Seroconversion Risk Factor Odds Ratio* 95% CI Deep injury Visibly bloody device Device in artery/vein Terminally ill SP AZT PEP *p<0.01 for all NEJM 1997;337:

7 Other Likely Risk Factors Viral Load Glove use 50% decrease in volume of blood transmitted Hollow bore vs solid bore large diameter needles weakly increased risk (p = 0.08) no documented cases to date of seroconversion from suture needles (though 3 from solid sharps) drying conditions tenfold drop in infectivity every 9 hours

8 Other Likely Risk Factors Survivability 10-fold drop in infectivity every 9 hrs Syringes of blood Viable virus at 42 days in 39 degree Fahrenheit 50% At 21 days in 68 degrees 8% At 7 days in 80 degrees - <1% Heimer R J of Substance Use and Misuse, 9/2000

9 NonOccupational Risk Factors Makerere and Columbia U data - Uganda 415 Discordant couples followed 30 months 90 of 415 seroconverted Viral Load below 1,500 copies (n=51) NO SEROCONVERSIONS Circumcised male partners (50/187) NO SEROCONVERSIONS Quinn T, Wawer M, Sewankambo N NEJM 3/30/00 Vol 342

10 Evidence of Efficacy of PEP animal models: high level of protection when started within 24 h multiple studies document reduced vertical transmission with PEP, independent of reduction of maternal viral load OR = 0.19 for AZT use in case-control study cases of seroconversion despite proper PEP imply that efficacy less than 100%

11 Risks of PEP More symptoms, less serious side effects than HIV infected persons on ARV common symptoms: HA, fatigue, malaise, GI disturbances, rash hepatotoxicity, bone marrow, pancreatitis, CNS effects, allergic reactions nevirapine: life threatening hepatotoxicity long-term: unknown

12 Timing of start of PEP? Theoretical considerations Animal data Experience in humans

13

14 Timing of PEP: what s the evidence? animal PEP studies: suggest substantially less effective beyond hours case-control study: most subjects in each group received PEP within 4 hours analysis of PEP failures does not suggest a clear cut-off

15 Timing of PEP: the N of 1 13 yo girl in Italy transfused w/ one unit of blood from donor in the window period seroconversion risk estimated to be virtually 100% 3-drug PEP initiated 50 hours posttransfusion, continued for 9 months no evidence of HIV infection 15 months later Ann Int Med 2000;133:31-4.

16 Timing of PEP Efficacy of PEP thought to wane with time, when is PEP no longer worth it? benefits of PEP risks of PEP exposure time

17 Timing of PEP: CDC Guidelines Initiate as soon as possible (within hours) Interval after which there is no benefit for humans is undefined If appropriate for the exposure, PEP should be started even when the interval since exposure exceeds 36 hours Obtain expert advice when interval has exceeded 36 hours MMWR 1998;47:RR-7.

18 Duration of PEP In animal studies, 3 days or 10 days of PEP inferior to 28 days 4 weeks (28 days) used in case-control study and recommended by CDC guidelines 9 months if you are an Italian girl posttransfusion

19 Back to the Case By report, the SP has never received treatment for his HIV. She does not know his VL or CD4 count, but he looks pretty healthy. The lancet was visibly bloody and stuck her through her glove, causing her to bleed Exam: pinpoint puncture wound on thumb What are your PEP recommendations?

20 PEP Regimens Moving Target Official guidelines versus clinical practice Balance concerns for resistance with toxicity and adherence Guidelines for Occupational and Non occupational exposure currently differ

21 PEP Regimens Basic Regimens two NRTIs simple dosing Expanded Regimens basic regimen plus PI or efavirenz or 3 rd NRTI may be more effective more potential for toxicity adherence more difficult

22 Basic Regimens: AZT/3TC Advantages AZT the best studied agent for PEP, with proven efficacy simple dosage: Combivir, one tab bid well-known & manageable side effects Disadvantages sides effects common, may impair compliance resistance to AZT & 3TC common

23 Expanded Regimens Efavirenz once daily dosing may improve adherence theoretically faster onset of action (does not require phosphorylation) CNS side effects common, can be difficult for health care workers rash common can progress to Stevens - Johnson Syndrome raises concern for acute seroconversion contraindicated in pregnancy

24 Back to the Case After extensive counseling, she decides to take Combivir basic regimen You write the prescription and arrange follow-up

25 Case Number 2 24 yo dental tech splashed in the eye during dental procedure 3 hours ago Source patient: 33 yo female, co-infected with HIV and HCV What more would you like to know?

26 Case number 2 continued Saliva was visibly bloody - in fact, it was mostly blood that splashed her she rinsed out her eye immediately source patient has never taken antiretrovirals, has a CD4 count of about 500 and a viral load of 20,000 last time it was checked. She is 8 weeks pregnant

27 Case number 2 continued What is her risk of contracting HIV? Of HCV? What are your PEP recommendations? How does her pregnancy affect your decision making?

28 Case 2 continued Risk of HIV from mucous membrane exposures: 0.09% (95% CI 0.006% -0.5%) Risk of HCV in this circumstance unknown; thought to be higher than HIV, because risk of HCV in percutaneous exposures, at 1.8%, is higher than that for HIV

29 PEP in Pregnancy Most antiretrovirals class B or C in pregnancy experience with AZT & 3TC largely reassuring avoid efavirenz (anancephaly in monkeys), amprenavir (ossification defects in rabbits), and indinavir (hyperbilirubinemia) theoretically higher risk of vertical transmission with primary HIV infection

30 Case 2 continued You decide on AZT/3TC/Nelfinavir 4 days later she calls complaining of headache, an itchy rash, and URI symptoms what do you do?

31 Case 2 continued Exam: VS: T 99.0 R 14 P 78 BP 134/76 Gen - alert, tired-appearing, no acute distress HEENT - nasal congestion, otherwise benign Neck - 3 ant cervical lymph nodes Lungs, cardiac, abdomen: benign Neuro: nonfocal Skin: urticarial rash on trunk and legs How would you manage her?

32 Primary HIV Infection most patients who contract HIV are symptomatic with seroconversion flu-like or mono-like illness often accompanied by a rash onset typically 3-4 weeks following exposure, but high variability growing evidence that treatment of PHI may have significant long-term benefit

33 Primary HIV Infection - Symptoms Fever 87% Rash 68% Pharyngitis 48% Myalgias 42% Headache 39% Diarrhea 32% Abdominal Pain 32% Arthralgias 29% Nausea/Vomiting 29%

34 Primary HIV Infection - Signs Axillary Temp > % Maculopapular Rash 63% Lymphadenopathy 57% Oral Ulcers 40% Genital Ulcers/Discharge 36% Purulent Sputum 6% Urticarial Rash 6% Meningismus 6%

35 PHI: Diagnostic Testing HIV RNA 1 mil 100,000 10,000 1,000 HIV RNA P24 + Ab + _ HIV-1 Antibodies Exposure Symptoms Days

36 Follow-up HIV Testing 1998 CDC recommendations: HIV Ab at 6 weeks, 3 months, 6 months rare case reports of seroconversion beyond 6 months new guidelines: consider testing at 12 months for serious exposures VL testing not recommended unless Primary HIV Infection (PHI) suspected

37 Hepatitis C Exposure average risk of seroconversion from percutaneous exposure 1.8% same risk factors as for HIV thought to apply gamma globulin not useful early recognition and treatment of HCV infection appears to improve odds of eradication

38 Hepatitis C: follow-up testing HCV Ab test at 6 months consider screening LFTs periodically or if symptomatic note that, unlike HIV, most patients are not symptomatic with acute HCV infection

39 NonOccupational PEP case 34 yo female s/p unprotected, nonconsensual vaginal intercourse with person of unknown HIV status what is her level of risk? what, if any, PEP would you recommend?

40 Exposure risks (average, per episode, from known (+) source) percutaneous (blood) HIV HCV HBV (eag+) HBV (eag-) 0.3% 1.8% 1 40%* %** mucocutaneous (blood).09% 2 receptive anal 0.1-5%*** v. low; unclear insertive anal 0.06% or less 3 v. low; unclear receptive vaginal % 4 v. low; unclear insertive vaginal % 5 v. low; unclear receptive oral-male.06% or less 6 v. low; unclear female-female orogenital contact 4 case reports 7 insertive oral? 1 case report v. low; unclear needle sharing 0.67% 8 very high vertical (no proph.) 24% 5-6% 9 breastfeeding ~ doubles risk of vert.transmission 10 has not been documented 11 *decreases to 2.4% if HBIG & vaccine given **decreases to 0% if HBIG & vaccine given. Hepatitis B vaccines also are 70%-88% effective when given within 1 week after HBV exposure. *** recent studies suggest approx 1% 12

41 npep Case Data is suggestive, but difficult to document failures in US studies MMWR January, 2005 Vol 54/RR-2 pilot study in San Francisco suggests that providing npep, when accompanied by counseling, does not lead to increased risky behavior

42 npep Case, continued Local epidemiology of HIV infections should guide advice on npep Realize that emotions and fear guide decisions in first few days As much as possible try to get HIV testing of SP Balance risk and benefit of treatment

43 PEP: Core Principles Evidence is limited, but suggestive Balancing of risks vs benefits Timing: the sooner the better, but interval beyond which no benefit is unclear 28 days is recommended. Optimal duration unclear Decision making can get very complex when resistance in SP suspected