POSTEXPOSURE PROPHYLAXIS
Bloodborne viruses Hepatitis B Hepatitis C HIV
Hepatitis B Risk of seroconversion HBeAg negative 2% HBeAg positive 20-40% If seroconvert most recover completely and develop immunity 10% becomes carriers Immunoglobulins Vaccine safe and effective (Engerix B)
Hepatitis C Risk of seroconversion 1.2-10% 80-100% of persons infected may become chronic carriers No vaccine available Immunoglobulins are ineffective
The type of fluid in significant exposure? The risk is related to: The type of fluid The presence of blood in the fluid The amount of blood The type of injury Possibly the duration of exposure Possibly the patient s viral load and clinical state Probably the HCW s immune status
Documented HIV transmissions All involved blood or bloody fluid Three exceptions: laboratory technicians exposed to HIV viral cultures No reported transmissions involving urine, stool, sweat, tears or other body fluids Exposure to saliva, tears, or non bloody urine or feces does not require PEP (Center for Disease Control (CDC) recommendations) No cases of documented HIV transmission have been reported with cerebrospinal-, synovial-, pericardial-, pleural-, peritoneal- and amniotic fluids A retrospective case-control study has shown that the larger the quantity or volume of blood exposure the greater the risk for HIV transmission
What exposure is significant? The estimated risk of HIV transmission with a single exposure from a HIV infected source Needle sharing 67/10 000 Percutaneous occupational exposure 30/10 000 Receptive anal intercourse 10 30/10 000 Receptive vaginal intercourse 8 20/10 000 Insertive vaginal sex 3 9/10 000 Insertive anal sex 3/10 000 Intravenous blood product 0.015/10 000
Type or severity of injury Most common form of reported exposure is the needle stick injury In the USA no confirmed reports of seroconversion of surgeons or suture needle injuries in HCWs The CDC has shown that the following increased the risk of acquiring HIV from a needle stick injury: Deep injury (not defined) odds ratio = 15 Visible blood contamination odds ratio = 6.2 Patient who died of AIDS within two months after exposure - odds ratio = 5.6 Needle placement in a vein or artery odds ratio = 4.3
Type or severity of injury Largest meta-analysis of HIV seroconversion risk after exposure to bloody fluid showed (before highly active antiretroviral therapy (HAART) was implemented): Needle stick injuries: 20 of 6135 exposures (0.33%) Mucosal exposure: 1 of 1143 exposures (0.09%) Skin exposure: no cases reported (0%)
Guideline "Best practice generally recommended"
Rationale of PEP for HIV Pathogenesis "Window of opportunity" Dendritic cells initial target 24-48h migration of cells to lymph nodes Within 5 days in peripheral blood Widespread dissemination follows
Rationale of PEP for HIV Efficacy of antiretrovirals Animal studies HIV-2 and SIV Retrospective case-control study AZT reduced risk with 79-81% Problems with prospective trials ACTG 076 MTCT reduced by 67%
Occupational PEP and HIV Three questions Type of source material? Type of exposure? HIV status of source?
Type of source material? Risk blood semen, vaginal secretions body fluids contaminated with visible blood cerebrospinal fluid sinovial, pleural, peritoneal or pericardial fluid amniotic fluid
Type of source material? No risk saliva tears sweat nonbloody urine or faeces vomitus
Type of exposure? Higher risk Percutaneous injury with hollow needle, deep puncture, blood on device, needle in artery/vein Lower risk Percutaneous injury with solid needle, superficial scratch Mucous membrane - eye, mouth Nonintact skin - chapped, abraded, dermatitis No risk Intact skin
Status of source? No Risk HIV negative Lower risk HIV positive with lower titre (asymptomatic, higher CD4) Higher risk HIV positive with higher titre (advanced disease, primary HIV infection, high viral load, low CD4)??? Unknown status or source - case by case basis
Exposure Management Exposure site Wash/rinse Expressing fluid no evidence Evaluate exposure Testing Counselling PEP Follow-up
PEP Exposure Prophylaxis No risk None Lower risk Basic regimen Higher risk Extended regimen Basic Regimen Zidovudine 10mg tds or 300mg bd Lamivudine 150mg bd Extended Regimen Basic regimen plus Indinavir (Crixivan ) 800mg q8h on empty stomach Or Nelfinavir (Viracept ) 750mg tds after meals Or Kalaetra 3 bd
Timing of PEP initiation ASAP (within hours) Interval after which no benefit undefined -?72h Special situations Resistance of source virus? Add third or fourth drug Pregnancy - Discussion!
Side-effects of PEP (NRTI's) Zidovudine Fatigue, malaise, headache, insomnia Nausea, asthenia Bone marrow suppression Lamivudine Headache Abdominal pain, diarrhoea Pancreatitis
Side-effects of PEP (Protease inhibitors) Indinavir Nephrolithiasis, crystalluria, hematuria Nausea Headache Elevated liver functions Hyperglycemia Increase fluid intake Nelfinavir Diarrhoea Hyperglycaemia Additional contraceptive measures
Monitoring and follow-up of injured Baseline Anti-HIV, Anti-HBs, Anti-HCV FBC, liver functions On prophylaxis FBC and LFT at 2 weeks and 4 weeks HIV serology HIV Elisa at 6 weeks, 3 months and 6 months (seroconversion usually after 3weeks 3 months) PCR HCV serology (if source seropositive or unidentified) Baseline and 6 months for anti-hcv Liver functions (baseline and 6 months)
Counselling Sexual abstinence/ condoms Don't donate blood Don't breastfeed Evaluate any acute illness
Other exposures Sexual assault /rape Human bite Abandoned needles Needle-sharing Blood transfusions Nosebleeds
PEP after sexual assault Antibiotic prophylaxis Hepatitis B prophylaxis HIV prophylaxis No data exists Incidence per sexual contact ± 1% Risk with rape 2-5% Use basic or extended regimen