Management>Antiretroviral Therapy>

DEFINITION

• Use of ART following exposure or potential HIV exposure to prevent HIV infection.

INDICATIONS

• Estimated 400,000 occupational exposures per yr in U.S.
• Estimated risk of transmission: 0.3% per needlestick exposure; 0.006% per mucous membrane exposure (CDC).
• 57 confirmed and 138 possible cases of HIV transmission via occupational exposure reported to CDC's voluntary reporting system through Dec 2001 (Henderson DK).
• Among 56 confirmed cases, occupation was nurses (23), lab techs (20), physicians (6). All transmissions involved blood or bloody body fluid except for 3 lab workers exposed to HIV viral cultures.
• Risk for seroconversion: deep injury, visible blood on device, needle placement in vein or artery, source with late stage HIV infection/high viral load (Do AN, Ciesielski CA, Metler RP, et al.).

• Retrospective case-control study showed 79% reduction in HIV transmission risk with AZT monotherapy (Do AN, Ciesielski CA, Metler RP, et al.).
• PEP failures been reported (Bassett IV, Freedberg KA, Walensky RP and Jaeckel E, Cornberg M, Wedemeyer H, et al.)
• Treatment duration: 4 wks.
• Animal data show that PEP initiated <24 hrs after exposure and extended for 28 days effective in preventing transmission of SIV in macaques. 1 wk PEP less effective than 4 wk treatment.

CLINICAL RECOMMENDATION

• 3-drug (2 NRTI + PI) regimen: high-risk exposure (i.e., deep penetrating stick with hollow bore needle/mucous membrane exposure to large volume of infectious fluid such as blood/CSF) AND source has symptomatic HIV infection, AIDS, acute seroconversion, or high VL.
• 2-drug (2 NRTI) regimen: less severe percutaneous injury and source has asymptomatic HIV infection or known HIV viral load of <1500.
• No PEP: HIV status or source unknown or source uninfected; however, consider 2-drug PEP if exposure to HIV+ person likely. Recommend HIV rapid testing of source in such cases.
• If concern for drug resistance: Initiate 3-drug prophylaxis without delay and consult HIV expert to assist in selection of drugs to which source's virus unlikely to be resistant. Important to rapidly obtain source information on treatment history and any genotypes.
• NRTI backbone (author opinion): AZT/3TC is standard NRTI backbone based on clinical data; TDF/FTC better tolerated and supported by animal data. d4T/3TC can also be used as an alternative. ddI/d4T in CDC guidelines but would avoid combination given toxicities.
• 3rd agent (author opinion): NFV used in older PEP literature but newer PIs likely to be better. LPV/r preferred as more likely to have activity against PI-resistant virus. Other boosted PIs (e.g. ATV + RTV, FPV + RTV, DRV + RTV) can be used if LPV/r not tolerated. (No data, but DRV + RTV may be more active than LPV/r if source patient has PI-resistant virus.) EFV can be used instead of PI but less data for PEP. NVP should not be used because of risk of serious hepatotoxicity in pts with normal CD4 counts.

• AZT: Established efficacy for PEP; high rates of GI intolerance, headache. Monitor CBC.
• 3TC: Used in most PEP regimens: potent, well tolerated, available coformulated with AZT (Combivir).
• d4T: good short term tolerability; do not combine with AZT.
• ABC: well tolerated but risk of hypersensitivity reaction (HSR) with short-term therapy; coformulated with AZT/3TC Trizivir) or 3TC (Epzicom). HLA B*5701 testing can be used to screen for HSR, but this would delay institution of PEP.
• ddI: must be taken on empty stomach; GI intolerance, especially with buffered form; enteric coated ddI preferred.
• TDF: potent, well tolerated, qd dosing; effective for PEP in primate studies.
• FTC: daily, similar to 3TC, available coformulated with TDF (Truvada).
• EFV: potent, but concern for short-term CNS toxicity in HCW.
• NVP: Avoid in PEP as 22 HCWs had serious adverse reactions (12 hepatotoxicity including 1 liver transplant, 14 skin reactions including Stevens-Johnson syndrome) (U.S. Public Health Service).
• LPV/r: potent, often active against PI-resistant virus, but may cause GI side effects.
• ATV+/- RTV: potent, well tolerated with qd dosing, lowest pill burden among PIs; food requirement, indirect hyperbilirubinemia w/ occcasional jaundice, requires RTV boosting with TDF co-administration.
• NFV: diarrhea, bid dosing, fatty food requirement.
• FPV +/- RTV: low pill burden, qd or bid dosing, no food restrictions. 
• DRV + RTV : may be most active against PI-resistant virus

• If acute seroconversion suspected in source, check source VL.
• Rapid test: Preferred method. Use of validated HIV rapid tests helpful when source pt's HIV status unknown and rapid determination needs to be made regarding use of PEP. Result available in <1 hr, highly reliable in ruling out HIV, cost effective, and reduces HCW anxiety.
• Standard testing: ELISA usually available within 72 hrs. Can discontinue PEP if negative ELISA.

• HCW testing: HIV serology at time of injury, 6 wks, 3 mos, 6 mos. Perform at 12 mos if HCV acquired with injury.
• Initiation of PEP: As quickly as possible, 1-2 hrs after injury up to 36 hrs.
• Side effects: 74% of HCWs experience side effects, including nausea, fatigue, headache, vomiting. Major reason for discontinuation before 4 wks (Braitstein P, Chan K, Beardsell A, et al. and Sulkowski MS, Ray SC, Thomas DL). AZT may be major contributor; TDF better tolerated.
• Pregnancy:does not preclude PEP, AZT, 3TC, d4T, LPV/r considered safest in pregnancy.
• Breastfeeding: consider temporary discontinuation during PEP.
• Prevent sexual transmission: Safer sex or abstain until negative serology at 6 mos. Greatest risk in first 6 to12 wks post injury.
• Resistance testing: not recommended as takes too long to obtain results. Instead, obtain source pt's viral load, ART history, and prior genotypes if available. Consult expert.
• Advise HCW to seek medical care for any acute illness that occurs during follow-up period (first 6 mos post injury). Risk of seroconversion highest within first 6-12 wks post injury.
• Recommend follow-up counseling, monitoring for symptoms/side effects at wk 1, 2, 4 and then follow-up with HIV testing at schedule above.

• HCW unvaccinated and source HBsAg+: recommend HBIG + vaccine series (3 doses).
• HCW unvaccinated and source unknown: vaccine series (3 doses).
• HCW vaccinated and known to be a responder (antibody to HBsAg >10 mIU/mL): No treatment.
• HCW non-responder and source HBsAg+ or high risk: HBIG x 1+ vaccine series or HBIG x2.
• HCW antibody status unknown: Test for anti-HBs and no Rx if anti-HBs >10mIU/mL. If <10 then HBIG x1 and vaccine booster if source HBsAg+ or HBV vaccine series and titer at 1-2 mos if source unknown.

• 1.9% transmission rate from sharps injury from HCV infected source (review of 25 studies) (U.S. Public Health Service).
• Source testing: anti-HCV; confirm positives with quantitative PCR.
• HCW: anti-HCV and ALT at time of injury and at 3-6 mos. Confirm positive serology with PCR.
• Consider HCV RNA at 4-6 wks to detect acute HCV prior to seroconversion (usually have asymptomatic elevation of ALT).
• Currently no prophylaxis with immune globulin or antivirals recommended.
• If HCV transmitted, refer to an expert because early treatment usually curative (Quirino T, Niero F, Ricci E, et al. and Cardo DM, Culver DH, Ciesielski CA, et al.).

• National Clinician's PEP hotline (HRSA, CDC, AETC): 1-888-448-4911 or http://www.ucsf.edu/hivcntr/Hotlines/PEPline.html.
• Hepatitis hotline: 1-888-443-7232 or http://www.cdc.gov/hepatitis.

REFERENCES

REFERENCED WITHIN THIS GUIDE

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