COMMENTARY

HIV Prophylaxis Following Occupational Exposure: Guideline and Commentary

Barry S. Zingman, MD

Disclosures

January 30, 2013

In This Article

Rationale for PEP

Several clinical studies have demonstrated that HIV transmission can be significantly reduced by the post-exposure administration of antiretroviral agents. A dramatic decline in vertical transmission was observed in the AIDS Clinical Trial Group (ACTG) 076 study,[1] in which pregnant women and their newborns received monotherapy with zidovudine (ZDV), and in the HIVNET 012 study,[2] in which single-dose nevirapine was compared with ZDV. A CDC retrospective case-control study[3] of ZDV use after occupational HIV exposure in healthcare workers (HCWs) showed an 81% reduction in risk of HIV infection in persons who received ZDV. This study also identified characteristics of both the exposure and the source patient that placed the HCWs at highest risk for HIV acquisition (see the section below entitled Risk Factors Associated With HIV Transmission).

Because the ultimate goals of PEP are to maximally suppress any limited viral replication that may occur and to shift the biologic advantage to the host cellular immune system to prevent or abort early infection, the Committee recommends the use of a three-drug PEP regimen for all significant risk exposures .

Experimental models of HIV infection demonstrate the following sequence of events: After percutaneous or mucosal exposure to HIV, local replication of virus occurs in tissue macrophages or dendritic cells; host cytotoxic T cells will kill productively infected target cells. However, if infection cannot be contained at this stage, it is followed within 2 to 3 days by replication of HIV in regional lymph nodes; viremia then follows within 3 to 5 days of virus inoculation. This sequence of events carries significant implications. Given the rapid appearance of productively infected cells following the introduction of virus, regimens with the most rapid onset of activity, multiple sites of antiviral action, and greatest strength are likely most effective.

In vitro evidence from a small study of HCWs who were exposed percutaneously to HIV but who did not seroconvert suggests that limited viral replication may occur without establishment of infection.[4] HIV-specific T-cell proliferative responses were observed in the majority of these individuals. Because the T-cell proliferative response is major histocompatibility complex (MHC) class I specific, limited viral replication within the tissue macrophages is inferred. This sequence of events also carries important implications. If limited HIV replication following exposure is a frequent event, then the argument to use a highly active PEP regimen (ie, three drugs) to maximize potency becomes even stronger.

Table 1. Estimated Per-Act Probability of Acquiring HIV From a Known HIV-Infected Source by Exposure Acta

Type of Exposure Risk per 10,000 Exposures
Parenteral
   Blood Transfusion[5]
   Percutaneous (needlestick)[6]
9,000
30
Other[7] b
   Biting
   Spitting
   Throwing body fluids (including semen or saliva)
Negligible
Negligible
Negligible

Modified from the Centers for Disease Control and Prevention. HIV Transmission Risk, fact sheet; July 2012. Available at http://www.cdc.gov/hiv/law/transmission.htm. a Factors that increase the risk of HIV transmission include early and late-stage HIV infection and a high level of HIV in the blood. Factors that reduce the risk of HIV transmission include low level of HIV in the blood and the use of ART. b HIV transmission through these exposure routes is technically possible but extremely unlikely and cases are not well documented.

Fifty-seven cases of documented seroconversion following occupational HIV exposure were reported to the CDC through 2010.[8] The most recent possible case of occupationally acquired HIV was reported to the CDC in 2009; however, no new documented cases have been reported since 1999.[8] The mean risk following an occupational percutaneous exposure is roughly 1 in 300 (0.3%). However, the mean risk may be significantly higher in cases in which more than one risk factor is present (eg, in persons who incur a deep injury with a hollow-bore needle from an HIV-infected patient with a high viral load). Although the effect of viral load level has not been studied in the setting of occupational exposures, studies have shown that the probability of sexually transmitting HIV is correlated with HIV viral load.[9,10,11] The risk of transmission can be expected to be increased in the setting of high HIV viral load levels in the source patient.

After a mucous membrane exposure, the average risk of seroconversion is approximately 9 in 10,000 (0.09%). In this analysis, the use of ZDV PEP by HCWs in the CDC study was shown to reduce the risk of HIV acquisition by 81%.[3]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....