Resistant HIV strains may undermine PEP regimens

Exposed workers should be given different drug

Synopsis: In a multicenter study of occupational HIV exposures, 38% of source patients had genotype mutations associated with resistance to anti-retroviral drugs. Recent antiretroviral treatment history was highly associated with resistance.

Source: Beltrami EL, et al. Antiretroviral drug resistance in human immunodeficiency virus-infected source patients for occupational exposures to health care workers. Infect Control Hosp Epidemiol 2003; 24:724-730.

Beltrami and colleagues enrolled health care workers (HCWs) with percutaneous exposure to HIV, along with source patients for the exposures, in tertiary care medical centers in five U.S. cities. They collected antiretroviral treatment histories from source patients. In addition, they collected source patients’ blood for RNA viral load. HIV-1 isolates were submitted for genotyping to identify mutations associated with primary drug resistance.

They enrolled a total of 64 HCW-patient pairs. Fourteen patients had undetectable viral loads, and thus virus was not available for genotyping. Of the 50 isolates genotyped, 19 (38%) had one or more (range: 1-6) mutations associated with primary drug resistance. Of the 50 patients, 26 had taken and 23 had not taken antiretroviral agents within the three months prior to the exposure incident. No drug treatment history was available from one patient. Of the 26 isolates from patients having received antiretroviral therapy, 16 (26%) had at least one primary drug resistance mutation. Of the 23 isolates from patients without recent antiretroviral treatment, three (13%) had at least one primary drug resistance mutation.

Multivariate analysis was performed on five drugs that are included in the Centers for Disease Control and Preventions' (CDC) current post-exposure prophylaxis (PEP) regimens: lamivudine, zidovudine, efavirenz, nevirapine, and nelfinavir.1

Resistance to a specific drug was related to current or previous (within three months) use of that drug or of another drug of the same class. The results were similar when agents used within the preceding year were analyzed. Beltrami, et al. recommend that when a health care worker sustains a percutaneous exposure from a source patient known to be HIV-positive, PEP should include one or more agents with which the source patient has not been treated. If that is not possible, an attempt should be made to select agents with which the source patient has not been treated within the preceding three months.

Comment by Robert Muder, MD, hospital epidemiologist, Pittsburgh VA Medical Center

Although an HCW’s risk of acquiring HIV infection after a percutaneous exposure to blood from an HIV-positive source patient is low (0.3%), the U.S. Public Health Service recommends the initiation of PEP to reduce the risk further.1

Although there are no controlled trials of PEP, the estimated efficacy is approximately 80%, based on indirect evidence and animal models.

The recommended regimes contain two or three antiretroviral drugs; ideally, PEP should be started within 24 hours of exposure. The relatively high prevalence of primary drug resistance mutations in HIV from patients who have received antiretroviral therapy could potentially compromise the efficacy of antiretroviral therapy. At the time of a percutaneous exposure incident, the viral genotype of the source patient is likely to be unavailable, and the appropriate testing can’t be performed within the 24-hour window in which PEP should be initiated.

Beltrami, et al. show evidence that the source patient’s recent history of antiretroviral therapy is highly correlated with the presence of primary drug resistance mutations. It’s not perfect; for example, 13% of treatment-naïve patients had virus with drug resistance mutations. Nevertheless, treatment history likely is to be obtainable in a timely fashion and offers at least a rational basis for adjusting the agents used in PEP. Whether such an approach will reduce the incidence of occupationally acquired HIV infection probably never will be demonstrated by a clinical trial, but at present, it seems to be a highly logical approach.

Reference

1. Centers for Disease Control and Prevention. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Morbid Mortal Wkly Rep 2001; 50(RR11):1-52.