BORDERNETwork Training on P ost- E xposure- P rophylaxis Dr. med. Wolfgang Güthoff / Alexander Leffers, M.A.

This presentation arises from the BORDERNETwork project which has received funding from the European Union, in the framework of the Health Program, and co- funding of the Ministry of Environment, Health and Consumer Protection of the Federal State of Brandenburg. The sole responsibility of any use that may be made of the information lies with the authors (SPI, AIDS-Hilfe Potsdam e.V.)

Table of Contents Transmission Conditions for PEP Guidelines on PEP Blood Control Problems with PEP

PEP HIV - Exposure When? Injury with HIV contaminated instruments Wetting of open wounds and mucosa with HIV contaminated fluids Unprotected sex with an HIV infected person Use of HIV contaminated needles (needle sharing) Transfusion of HIV contaminated blood or blood products Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

PEP - Guidelines The ultimate goal of PEP is: to suppress any viral replication that may occur, to shift the biological advantage to the host cellular immune system to prevent or abort early infection content/uploads/2009/05/pep_card.pdf m

Occupational PEP Probability of Transmission Factors influencing transmission: Kind of transmitting material (Viral concentration is highest in the blood) Kind of exposure: Hollow needle Cut injury Open wound Exposure of mucosa Viral concentration from index person Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

Average risk: Percutaneous 0.3% Mucous membrane 0.1% Non-intact skin<0.1% Blood transmission100% (non occupational course – unprotected sex 0,03 – 7,5%) Occupational PEP Probability of Transmission Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

Risk for an HIV-Transmission depending on Exposure in Relation to Average Risk Kind of Exposure Exposition Risk in Relation to Average Risk Very deep injury16 : 1 Visible blood at instrument5 : 1 Index person has high viral load6 : 1 Exposure of mucosa1 : 10 Exposure of damaged skin1 : 10 Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

Occupational PEP Probability of Transmission High Risk deep parenteral inoculation via hollow needle parenteral inoculation with high viral titers Less Risk injuries via non-hollow needle mucosal exposure/non-intact skin exposure Risk not identified intact skin exposure exposure to urine, saliva, tears, sweat

Exposure Risk Little information on efficacy of PEP in humans Seroconversion infrequent following occupational exposure to HIV- infected blood Use of Zidovudine (ZDV) was associated with an 81% decrease in the risk for HIV infection limitations include a small number of cases, and that cases and controls came from different cohorts (Cardo et al, NEJM 1997;337: )

PEP - Conditions contact with relevant risk of transmission between an HIV-negative Person and an HIV- infected Person (Index person) Negative HIV-Test in exposed Person is a condition for PEP HIV- Rapid Test of Index person HIV Rapid Test available?

PEP - Counselling and Decision (two physicians should get knowledge and experience in this field in every hospital) Estimation of risk Decision for PEP: strongly encourage recommend offer do nothing (counselling is important that the exposed person is assured) Counselling for PEP encloses: no blood donation for 12 month safer sex until getting final HIV test after six month drugs do not have an apply for this indication written confirmation

Occupational PEP Immediate Measures Measurements at cut injuries or needle sticks disinfection, wash it with soap and water Mucosa membrane exposure Douche of oral cavity with 70% alcohol: mouth wash 5 times for 15 seconds Douche of eyes with running water Non intact skin Wash with soap, water and antiseptic Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

Post exposure Prophylaxis (PEP) PEP after occupational HIV-Exposition Transdermal injury with contaminated hollow needle strongly encourage Superficial injury (f. e. with surgery needle) offer Contact of damaged skin with blood offer Contamination of intact skin do not recommend Contamination of mucosa membrane with blood recommend Contamination of mucosa membrane with urine or saliva do not recommend Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

PEP – when to start and time limits Entry and Fusion2h DNA-Integration in nucleus12h Viral replication after another12h PEP within 24h (best - start within first 2h) >72h after Exposition: PEP is not practical Replication of HIV and Targets of Therapy Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

Medications for PEP (German – Austrian Guidelines) Tenofovir 300mg plus Emtricitabin 200mg as combination product (Truvada 1x1 pill) combined with Kaletra (Lopinavir + Ritonavir) 2 x 400/100mg or Sustiva 1 x 600mg Alternative: Combivir 2 x 1 pill (Zidovudin + Lamivudin) Alternative: Invirase (2 x 1000mg plus Ritonavir 2 x 100mg) or Fosamprenavir Indinavir Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

European Guidelines HIV- rapid test from Index person If Index persons HIV-RNA > 1000 copies/ml – testing of drug resistance Start PEP if possible within 4h and not later then 48h Duration: 4 weeks Medication: Truvada (TDF/FTC) 1 x 1 pill Alternative: Combivir (ZDV/3TC)2 x 1 pill + Kaletra (LPVr) 2 x 2 pills Alternative: Invirase 500(SQV) 2 x2 capsules and Norvir (RTV) 2 x 100mg Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V. und der Österreichischen AIDS- Gesellschaft (ÖAG) et al., in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33.

Blood Controls Serologic control (HIV, possible HBV, HCV): at the start after 6 weeks, after 3 month after 6 month Laboratory tests: at the start, after 2 weeks and after 4 weeks: Blood count, liver enzymes, kidney function, blood sugar, urine

Problems regarding HIV – PEP Pregnancy and lactation period No substance is harmless! PEP only at high risk Experience only with Retrovir and Epivir Sustiva (Efavirenz) is contraindicated!

Period between exposition and starting PEP not longer than 24 h Problems regarding HIV – PEP

High risk through massive inoculation of infections material

Problems regarding HIV – PEP Strong side effects of HAART (mental – Efavirenz)

Problems regarding HIV – PEP Index person gets HAART and drug resistance is probable Course of CD4 cells Opportunistic infections (OI)

HIV-Infection known? How fast is an HIV-test possible? HIV- rapid tests every time for every physician available? PEP - Index person

Treatment Algorithm Did an exposure to a potentially HIV-infected fluid occur? Did a significant risk of transmission of HIV occur? (Contact of a HIV negative person with an HIV positive person (index person/source patient) Is the patient presenting within ideally 2 hours, not later than 72 hours of the exposure? Can the source patient be interviewed? Initiation of PEP regimen: PEP within 24h (best - start within first 2h) HIV monitoring YES NO No indication of PEP No follow-up needed No indication of PEP No follow-up needed PEP not indicated Follow-up HIV testing Adopted from: New York State Department of Health/ AIDS Institute: Recommendations for HIV Postexposure Prophylaxis (PEP) URL: Adopted from: Postexpositionelle Prophylaxe der HIV-Infektion. Gemeinsame Empfehlung der Deutschen AIDS-Gesellschaft (DAIG e.V.) und der Österreichischen AIDS-Gesellschaft (ÖAG) et al. in: Dtsch Med. Wochenschr 2009; 134: S 16-S 33. If yes: interview on HIV status or infection risk, resp. test/rapid test on HIV If no: belongs the source patient to a high risk group (with high prevalence) If yes: Individual benefit-risk assessment If no: PEP not indicated Serological test of source patient is confirmed HIV negative no evidence of acute retroviral syndrome Serological test of source patient is confirmed HIV positive Evidence of acute retroviral syndrome occurs Source patient is unknown, unwilling etc. Stop PEPContinue PEP for 4 weeks