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To the Editor: Health care workers (HCWs) are a group at significant risk for human immunodeficiency virus (HIV) infection through occupational exposure.¹ Guidelines from the US Public Health Service on the management of occupational exposure to HIV recommend antiretroviral postexposure prophylaxis for HCWs with occupational exposure associated with a risk for HIV transmission.² The recommended regimen includes zidovudine and lamivudine, with or without indinavir or nelfinavir, depending on the type of exposure. The guidelines also include management of occupational exposure with suspected drug-resistant HIV. Alternative regimens are not specified, but should be based on the likelihood that the source patient's HIV isolate will be susceptible to the postexposure prophylaxis. Limited data exist on the prevalence of mutations conferring antiretroviral resistance in HIV isolates from patients involved in HCW occupational exposure.² To address this issue, we evaluated source patient HIV isolates for antiretroviral resistance mutations.

Methods.
Twenty-two patients infected with HIV (1993-1996) who were involved as source patients in HCW occupational exposure at Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill, were enrolled. Inpatient and outpatient medical records of the source patients were reviewed for antiretroviral therapy history and CD4 cell counts. Genotypic analysis (performed at the University of Colorado Health Sciences Center, Denver) of HIV reverse transcriptase and protease sequences was performed on cultured isolates of HIV³ using the HIV GeneChip technology (Affymetrix Inc, Santa Clara, Calif).⁴ The study was approved by the human investigation committee of Rush Medical College.

Results.
Clinical information and HIV isolates were available for analysis from 15 source patients. Ten of the 15 had received antiretroviral therapy; 10 had received zidovudine, 5 didanosine, 3 lamivudine, 2 zalcitabine, 2 stavudine, and 1 nevirapine. No patients received protease inhibitors. Resistance mutations in the reverse transcriptase gene are shown in Table 1. Overall, isolates from 9 of 15 patients had resistance mutations in either the reverse transcriptase or protease gene. Eight of 10 zidovudine-treated patients had resistance mutations, as did 2 of 5 patients treated with didanosine, 2 of 3 patients treated with lamivudine, and the 1 patient treated with nevirapine. Substitutions thought to represent polymorphisms were noted at codon 100 in 1 patient and at 103 in 2 patients. No resistance mutations were detected in reverse transcriptase sequences from antiretroviral-naive patients. One isolate from a treatment-naive patient had an L90M mutation in protease, which has been associated with resistance to saquinavir.⁵ CD4 cell counts were available for 14 patients and were not significantly different in those with or without resistance mutations (1.2 x 10⁹/L vs 1.20 x 10⁹/L cells [121 vs 120 cells/µL]). Four exposed HCWs were treated with postexposure prophylaxis (3 zidovudine, 1 stavudine). None became infected with HIV.

View this table: [in this window] [in a new window] Table. Antiretroviral Resistance-Associated HIV-1 Reverse Transcriptase Gene Mutations

Comment.
In this study, we documented a high prevalence of genotypic mutations associated with antiretroviral drug resistance in isolates from HIV-infected patients involved in occupational exposure of HCWs. The presence of mutations associated with reverse transcriptase inhibitor therapy was seen only in patients who received antiretroviral therapy. Clinical stage of disease did not appear to be associated with the presence or absence of resistance mutations. Transmission of resistant HIV has been reported, including 2 cases acquired through occupational exposure.² Given the increasing utilization of combination antiretroviral therapy, and the growing number of patients harboring drug-resistant virus, the potential exists for HCWs to become infected with multidrug-resistant HIV through occupational exposure.

How do these data influence the management of the HCWs with an occupational exposure to a patient with suspected antiretroviral resistant HIV, eg, a patient failing antiretroviral therapy? Testing source patient HIV isolates for antiretroviral resistance would be of no immediate value, as postexposure prophylaxis should be initiated within hours of the exposure.² The treatment history may be helpful in predicting which resistance mutations might be present in the source isolate. We now include in our management strategy a rapid analysis of the source patient's treatment history and the efficacy of their current regimen in deciding on a postexposure prophylaxis regimen.

AUTHOR INFORMATION
Acknowledgment: We would like to thank Minoo Bakthiari, MSc, for performing the nucleotide sequencing, and Dave Shugarts, MSc, and Russell Young, MSc, for assistance in sample processing and virus culture.

Paul C. Tack, MD; James W. Bremer, PhD; Alan A. Harris, MD; Alan L. Landay, PhD; Harold A. Kessler, MD
Rush Medical College
Chicago, Ill

Daniel R. Kuritzkes, MD
University of Colorado Health Sciences Center
Denver

1. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroprevalence in health care workers after percutaneous exposure. N Engl J Med. 1997;337:1485-1490. FREE FULL TEXT 2. Centers for Disease Control and Prevention. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep. 1998;47(RR-7):1-33. 3. Division of AIDS, National Institute of Allergy and Infectious Diseases. 1997 DAIDS Virology Manual for HIV Laboratories. Washington, DC: US Dept of Health and Human Services; 1997. Publication NIH-97-3828. 4. Pease AC, Solas D, Sullivan EJ, Cronin AT, Holmes CP, Fodor SPA. Light-generated oligonucleotide array for rapid DNA sequence analysis. Proc Natl Acad Sci U S A. 1994;91:5022-5026. FREE FULL TEXT 5. Schinazi RF, Larder BA, Mellors JW. Mutations in retroviral genes associated with drug resistance. Int Antiviral News. 1997;4:2-14.

Edited by Margaret A. Winker, MD, Deputy Editor, and Phil B. Fontanarosa, MD, Interim Coeditor.

JAMA. 1999;281:1085-1086.

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