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Antiretroviral Post-Exposure Prophylaxis (PEP) for Occupational HIV Exposure
Global Health Sciences Literature Digest
Published March 12, 2007
Journal Article

Young T, Arens F, Kennedy G, Laurie J, Rutherford G. Antiretroviral Post-Exposure Prophylaxis (PEP) for Occupational HIV Exposure. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002835.

Objective

To conduct a systematic review to evaluate the effectiveness of antiretroviral post-exposure prophylaxis (PEP) on occupational exposure to HIV.

Search Strategy

The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AIDSearch, and the Database of Abstracts of Reviews of Effectiveness were searched from 1985 to January 2005 to identify controlled trials and analytic observational studies.Comparisons of two types of PEP regimens, as well as comparisons of PEP to no intervention were included. Descriptive studies without comparison groups and studies of PEP among sex workers were excluded. Occupational exposure was defined as being exposed to a potentially infectious product or substance, through a needlestick or mucous membrane exposure, in an occupational setting when the HIV status of the source patient is positive or unknown. References from retrieved studies were reviewed and experts in the field of HIV prevention were contacted. There was no language restriction.

Studies

No randomized controlled trials were identified. Only one observational case-control study conducted to identify risk factors for HIV transmission to a health-care worker (HCW) after percutaneous exposure met original inclusion criteria.(1) No studies designed to evaluate HIV incidence included two or more anti-retroviral therapies. There were 8 observational studies addressing adherence to and complications of PEP.

Participants

The single case control study included 33 HCW from the U.S., France, Italy and UK, with documented occupational percutaneous exposure to HIV-infected blood and subsequent HIV seroconversion; the 679 controls were HCW with documented exposure and absence of seroconversion 6 months later. The eight studies addressing adherence and complications of PEP evaluated a total of 3868 persons, all in developed countries (U.S., Italy and Great Britain).

Interventions

In the case control study, PEP consisted of zidovudine, with the majority of cases and controls taking at least 1000 mg per day; 66% of controls and 89% of cases took the first dose within four hours after exposure; 66% of controls and 44% of cases continued taking zidovudine for at least four weeks. The eight descriptive studies evaluated adherence and complications of therapy of a variety of ART drug regimens; these were primarily combination therapies, although one study (n= 647 persons) included zidovudine monotherapy.

Outcome Measures

The primary outcome measure was incidence of HIV infection among those taking PEP versus placebo, or incidence among those taking different PEP regimens. Secondary outcomes were adherence to and complications of PEP.

Results

Incidence of HIV infection: In the case-control study, cases had significantly lower odds of taking zidovudine after exposure compared to controls (OR 19, 95% CI 0.06 to 0.52), although there was no difference in the rates at which cases and controls were offered PEP. Adherence and complications: A combined analysis of 3 studies indicated that adverse events were more frequent among those taking a three-drug vs two-drug regimen, particularly regimens that included indinavir (combined OR 1.75 95% CI 1.41-2.17). Discontinuation rates were also slightly higher, although not statistically different, among those taking three-drug regimens (combined OR=1.21, 95% CI 0.94-1.55).

Conclusions

This review confirmed findings that adverse events were higher with a three-drug regimen, although discontinuation rates were similar. Zidovudine monotherapy may be effective in preventing HIV acquisition following occupational exposure. Because of the lack of appropriate trials, there is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV; however, based on the results of treatment, combination drugs could be used for PEP.

Quality Rating

Based on the QUOROM grading system for systematic reviews, this review was of high quality. The review was limited by the small number of studies, the lack of any controlled trials, and the reliance on descriptive studies not designed to evaluate HIV incidence. Only two of the eight comparative studies on adverse events reported rigorous methods for detecting the reported adverse events. Five of the eight studies did not include the total number of participants included in the analysis.

In Context

PEP is used to inhibit replication of an initial HIV inoculum to prevent establishment of chronic HIV infection, and is recommended for occupational exposure in many countries. This review demonstrates that there are limited rigorous studies evaluating its efficacy, primarily because a placebo controlled randomized trial would not be ethical. Indirect evidence for reduced seroconversion can be drawn from individual animal studies (Mori 2000, Tsai 1998) and prevention of mother to child transmission studies (Brocklehurst 2002, Taha 2003). Surveillance studies have also reported that adverse events are higher with three-drug regimens, particularly those containing indinavir.

Programmatic Implications

A four-week regimen of PEP should be initiated as soon as possible after occupational exposure, depending on the risk of seroconversion. CDC guidelines recommend two drugs for most HIV exposures and an expanded regimen with a third drug for exposures that pose an increased risk of HIV acquisition (exposure to large volumes of blood, deep injuries, blood containing particularly high levels of HIV, or detectable viral load in a source patient currently on treatment).(2,3) Health care workers should be counseled about expected adverse events and strategies for managing them.

References

  1. Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS, Bell DM. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997 Nov 20;337(21):1485-90.
  2. 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 2001; 50(RR-11).
  3. Centers for Disease Control and Prevention. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR 2005; 54(RR-9).