Infectious Diseases Section, VA Medical Center and George Washington University, Washington, District of Columbia, USA.
Received 25 August, 2008
Revised 2 September, 2008
Accepted 5 September, 2008
Correspondence to M.O. Siegel, MD, ID Section, VA Medical Center (151B), 50 Irving Street, NW, Washington, DC 20422, USA. Tel: +1 202 745 8301; fax: +1 202 745 8432; e-mail: email@example.com
An ‘expanded regimen’ of postexposure prophylaxis (PEP) is recommended for all high-risk occupational exposures to HIV-infected blood. This includes exposure to a high volume of inoculum, ‘deep’ injuries, injuries with a device that has been used in an HIV-infected patient's artery or vein, or blood containing a high HIV viral load [1,2]. However, designing an effective PEP regimen for occupational exposure to virus with extensive antiretroviral drug resistance may be particularly challenging. Raltegravir is the first agent in a new antiretroviral class, the integrase inhibitors. Currently, it is only approved for use in treatment-experienced HIV patients with multidrug resistance and has generally been well tolerated with few side effects. However, clinical trials are currently underway looking at raltegravir use in treatment-naive HIV patients . There have been no reports of raltegravir use in PEP in the literature, and no reports of adverse events to The National Clinicians' Post-Exposure Prophylaxis Hotline. We incorporated raltegravir in PEP regimens for two employees at the VA Medical Center, District of Columbia (VAMC-DC) after high-risk blood-borne exposures to resistant virus.
In a 7-month period from July 2007 to January 2008, there were two blood-borne exposures at our institution to the same HIV-infected patient, who had extensive mutations in the reverse transcriptase and protease genes by TRUGENE HIV-1 Genotyping Kit (Siemens Healthcare Diagnostics, Tarrytown, New York, USA) and by vircoTYPE HIV-1 (Virco Lab, Inc., Bridgewater, New Jersey, USA). The first exposure resulted from a scalpel laceration to the hand of a female surgical resident during central venous access catheter placement. At the time of the exposure, the source patient's HIV viral load was 215 000 copies/ml. The patient's viral genotype and virtual phenotype from 2 months prior revealed multiple thymidine analogue-associated mutations and a T69D insertion complex conferring resistance to all nucleoside reverse transcriptase inhibitors, a G190A mutation conferring resistance to all non-nucleoside reverse transcriptase inhibitors, multiple mutations associated with etravirine resistance and extensive mutations in the protease gene associated with resistance to all protease inhibitors tested. As raltegravir had not yet received US Food and Drug Administration (FDA) approval for clinical use, Merck and the Institutional Review Board permitted its compassionate use for PEP. Raltegravir was added to the initial regimen of emtricitabine/tenofovir, atazanavir, and ritonavir. However, she rapidly developed a very serum high bilirubin level and nausea resulting in the discontinuation of the atazanavir and ritonavir. The resident remained on emtricitabine/tenofovir and raltegravir for 28 days and tolerated this regimen without side effects.
The second exposure occurred in a laboratory technologist whose hand was punctured by a capillary tube filled with this HIV-infected patient's blood. The technologist was started on emtricitabine/tenofovir, ritonavir, darunavir and raltegravir and also tolerated the regimen without side effects. More than 6 months after their exposures, neither of the employees has had evidence of HIV seroconversion.
Raltegravir was well tolerated in these two occupational exposures and appears to be an optimal choice for these individuals exposed to blood from an HIV patient with extensive drug resistance, given its novel mechanism of action, potent and rapid HIV killing [3,4] and favorable side-effect profile. There are currently no published data to advocate routine raltegravir use in PEP and the severe nevirapine toxicity experience in PEP  remind us of the importance of caution. However, broader use of raltegravir since FDA approval and further safety data in treatment-naive patients with HIV infection may provide future rationale to expand its use for PEP.
M.O. Siegel, V.L. Kan and D.A. Benator were involved in the care of both healthcare workers. Dr Siegel is the first author and writer. Dr Kan and Dr Benator reviewed and revised the correspondence.
1. Panlilo A, Cardo D, Grohskopt L, Heneine W, Ross C. Updated U. S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005; 54(No. RR-9):1–17.
2. Notice to Readers: Updated information regarding antiretroviral agents used as HIV postexposure prophylaxis for occupational HIV exposures. MMWR 2007; 56:1291–1292.
3. Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, et al. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naïve patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr 2007; 46:125–133.
4. Sedaghat AR, Dinoso JB, Shen L, Wilke CO, Siliciano RF. Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle. Proc Natl Acad Sci USA 2008; 105:4832–4837.
5. US Department of Health and Human Services. Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures: worldwide, 1997–2000. MMWR 2001, 49:1153–1156.
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