Genotypic analysis of HIV isolates for antiretroviral resistance mutations from source patients involved in occupational exposures

Current CDC recommendations for the management of health care workers (HCW) with high risk occupational exposures (OE) to HTV infected body fluids include postexposure prophylaxis (PEP) with ZDV, 3TC, ± indinavir. There are limited data on the prevalence of mutations conferring antiretroviral resistance in HIV isolates from patients involved in HCW OE. We have evaluated 14 HTV source patient isolates for the presence of reverse transcriptase (RT) mutations associated with resistance to nucleoside and nonnucleoside RT inhibitors. Isolates were available from 1993 (1), 1994 (7), 1995 (3), and 1996 (3). Resistance mutations were determined utilizing the Affymetrix® (v2.0) system. All available source patient in/outpatient records were reviewed for antiretroviral therapy history (≥4 weeks therapy), outcomes, and CD4 cell counts at or around the time of the OE. 10 of 14 patients had been treated with antiretrovirals (ZDV.10; ddI, 5; ddC, 2; d4T, 2; 3TC, 3; nevirapine, 1). 8 of 10 treated vs. 0 of 4 untreated patients had RT resistance mutations. No mutations for ddC or d4T were identified. RT mutations were identified for 8 of 10 patients treated with ZDV, 2 of 5 with ddl, 2 of 3 with 3TC, and 1 of 1 with nevirapine. 3 non-drug related mutations at positions 100(1) and 103(2) were also identified. CD4 counts were available from 13 patients. The median CD4 cell count for patients with mutations was 9 cells/ul (range 0-485) vs. 169 cells/ul (range 0-401) for those with no mutations. These data suggest there is a high prevalence of reverse transcriptase inhibitor resistance mutations in antiretroviral treated source patients widi advanced HIV disease involved in HCW OE. Decisions regarding recommendations for HCW postexposure prophylaxis regimens may need to be modified based upon these and future observations.