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Health-care
workers (HCWs) are potentially at risk for human immunodeficiency
virus (HIV) infection through occupational exposures to blood.
Although prospective studies indicate that the estimated risk for
HIV infection after a percutaneous exposure to HIV-infected blood is
approximately 0.3% (1,2), factors that influence this risk have not
been determined. To assess potential risk factors, CDC, in
collaboration with French and British public health authorities,
conducted a retrospective case-control study using data reported to
national surveillance systems in the United States, France, and the
United Kingdom.
This report
describes the study and summarizes results that suggest that risk
factors for HIV transmission include certain characteristics of the
exposure and the source patient; in addition, postexposure use of
zidovudine (ZDV) by HCWs was associated with a lower risk for HIV
transmission. *
Case-HCWs had a
documented occupational percutaneous exposure to HIV-infected blood
(i.e., a needlestick or a cut with a sharp object {e.g., scalpel or
lancet}), HIV seroconversion temporally associated with the
exposure, and no other concurrent exposure to HIV. Control-HCWs had
a documented occupational percutaneous exposure to HIV-infected
blood and were HIV seronegative at the time of exposure and at least
6 months later. Case-HCWs were identified through reports to
national surveillance systems for occupationally acquired HIV
infection operated by CDC, in cooperation with state and local
health departments (United States), the National Public Health
Network (Reseau National de Sante Publique) (France), and the Public
Health Laboratory Service Communicable Disease Surveillance Center
(United Kingdom). Control-HCWs were identified through reports to a
passive surveillance project maintained by CDC since 1983 that
includes data from approximately 300 health-care institutions in the
United States (1).
The study
included all case-HCWs reported in the United States whose exposure
occurred during January 1988-August 1994 and all control-HCWs
exposed after January 1988 whose 6-month follow-up evaluation was
completed as of August 1994. Case- and control-HCWs reported in the
United States before 1988 were excluded from the analysis because
information on some variables was not routinely collected and
because postexposure use of ZDV was infrequent before 1988 (1). For
similar reasons, analysis was limited to case-HCWs reported in
France since 1990 and in the United Kingdom since 1989.
Information
obtained about HCWs included age; sex; occupation; work location;
and whether postexposure antiretroviral agents were offered, whether
they were used, how long after the exposure the first dose was used,
daily dosage, and duration of treatment. Information about source
patients included stage of HIV infection (acquired immunodeficiency
syndrome {AIDS}, symptomatic, or asymptomatic), use of
antiretroviral drugs at the time of the HCW's exposure, and presence
of terminal illness (i.e., death because of AIDS within 2 months
after the exposure). Information about exposures included the type
of device involved, gauge of hollow-bore needle, type of procedure
being performed, whether the procedure was an emergency, use of
gloves, time from use of the device to exposure, presence of visible
blood from the source patient on the device, and severity of injury.
Severity of injury was defined as superficial (surface scratch, no
blood appeared), moderate (penetrated skin and blood appeared), or
deep (deep puncture or wound with or without bleeding).
The study
included 31 case-HCWs (23 from the United States, five from France,
and three from the United Kingdom) and 679 control-HCWs (who were
from 190 of the reporting health-care institutions). Of the 31
exposures sustained by case-HCWs, 29 (94%) were needlesticks (all
with hollow needles) and two (7%) involved other sharp objects. Of
the 679 exposures sustained by control-HCWs, 620 (91%) were
needlesticks (including 594 hollow and 26 solid needles) and 59 (9%)
involved other sharp objects.
For both case-
and control-HCWs, 74% were exposed during 1990-1994, when ZDV
postexposure use had become more common (1). During 1990-1994, 17
(81%) of 21 case-HCWs had been offered ZDV, and from September 1990
(when collection of information on whether ZDV was offered to
control-HCWs became routine) through 1994, 268 (79%) of 338 control-HCWs
were offered ZDV. ZDV postexposure prophylaxis was used by nine
(29%) case-HCWs and 247 (36%) control-HCWs (crude odds ratio=0.7;
95% confidence interval {CI}=0.3-1.7). Regimens for case- and
control-HCWs generally were 1000 mg/day for 3-4 weeks; the small
number of case-HCWs who used ZDV precluded assessment of differences
in ZDV regimens between case- and control-HCWs.
All variables
that were statistically significant in the univariate analysis and
variables potentially important for prevention (e.g., use of gloves,
whether ZDV was offered, and whether ZDV was used) were examined
using logistic regression analysis. Based on this analysis, factors
associated with HIV transmission included a deep injury, device
visibly contaminated with the source patient's blood, procedures
involving a needle placed directly in a vein or artery, and terminal
illness in the source patient. In addition, case-HCWs were
significantly less likely to use ZDV than control-HCWs (adjusted
odds ratio=0.2, p less than 0.01) (Table_1) **. The crude odds ratio
for ZDV use differed from the adjusted odds ratio because ZDV use
was more frequent, among both case- and control-HCWs, for exposures
characterized by the other factors. All factors in the model also
were significant when the analysis was restricted to case-HCWs from
the United States.
The degree of
susceptibility to ZDV of HIV strains from source patients and case-HCWs
is unknown. Information about antiretroviral treatment for source
patients was available for seven case-HCWs and 124 control-HCWs who
had used ZDV; five (71%) case-HCWs and 87 (70%) control-HCWs were
exposed to blood from source patients who had been receiving ZDV at
the time of the exposure.
Reported by:
State and territorial health depts. CDC Cooperative Needlestick
Surveillance Group. D Abiteboul, MD, Institut National de Recherche
et de Securite and Groupe d'Etude sur le Risque d'Exposition au
Sang, Paris; F Lot, MD, Reseau National de Sante Publique, Saint
Maurice, France. J Heptonstall, MRCPath, Public Health Laboratory
Service Communicable Disease Surveillance Center, London, United
Kingdom. Div of HIV/AIDS Prevention, National Center for Prevention
Svcs; Hospital Infections Program, National Center for Infectious
Diseases, CDC.
Editorial Note
Editorial Note:
The findings in this report indicate that, among the HCWs in this
study, an increased risk for HIV infection following percutaneous
exposures to HIV-infected blood was associated with three factors.
First, the risk increased if the exposure involved a larger quantity
of blood, indicated by 1) a device visibly contaminated with the
patient's blood, 2) a procedure that involved a needle placed
directly in a vein or artery, or 3) a deep injury. Second, the risk
increased for exposures to blood from source patients with terminal
illness, probably reflecting the higher titer of HIV in blood late
in the course of AIDS or other factors, such as the presence of
syncytia-inducing strains of HIV (3,4). Finally, the analysis of
these data suggested that use of ZDV postexposure may be protective
for HCWs. After controlling for other factors associated with HIV
transmission risk, the model indicates that the risk for HIV
infection among HCWs who used ZDV was reduced by approximately 79%
(95% CI=43%-94%) (based on adjusted odds ratio=0.21; 95%
CI=0.06-0.57). However, the limitations of the study design must be
considered when interpreting these results.
A retrospective case-control study is not the
optimal study design for assessing ZDV efficacy. The optimal
approach – a prospective, placebo- controlled trial -- has not been
possible because of the requirement for a large number of HCWs and
the relatively low rate of HIV seroconversion following occupational
exposure (1). The findings of this study also are subject to
at least five
potential limitations. First, case- and control-HCWs were identified
using different data sources. Second, if control-HCWs were more
likely to have been offered or encouraged to use ZDV, then use of
the drug might be statistically associated with lack of HIV
seroconversion, even if ZDV is not truly protective; however,
available evidence does not suggest that control-HCWs were more
likely than case-HCWs to have been offered ZDV. Third, reporting
bias may have resulted if HCWs preferentially reported exposures
that they believed were more likely to result in HIV transmission;
this tendency presumably would be similar for case-HCWs and control-HCWs.
Fourth, ascertainment bias may have affected some data, particularly
subjective variables such as severity of injury, because information
for control-HCWs was obtained prospectively soon after exposure but
information for most case-HCWs was obtained after HIV seroconversion;
however, for most variables evaluated, objective documentation from
incident reports and medical records was available. Finally, number
of case-HCWs evaluated was small.
Although
failures of postexposure ZDV to prevent HIV infection in HCWs have
been documented (1), this is the first study of HCWs exposed to HIV
that assesses the effectiveness of ZDV as postexposure prophylaxis.
Studies involving animals have yielded inconclusive results (5). In
studies involving humans, ZDV was reported to reduce the rate of
perinatal HIV transmission (6) and to be beneficial in treating
early HIV infection (7); however, the implications of these results
for postexposure prophylaxis are uncertain. The short-term toxicity
of ZDV in HCWs primarily has been gastrointestinal discomfort and
fatigue (1,2,5,8).
ZDV is not
approved by the Food and Drug Administration for use as postexposure
prophylaxis. In a previous statement, the Public Health Service
(PHS) concluded that a recommendation could not be made for or
against the use of ZDV postexposure prophylaxis because of limited
knowledge regarding its efficacy and toxicity (9). PHS recommends
that HCWs who may be at risk for occupational exposure to HIV
infection be informed of the considerations pertaining to the use of
ZDV for postexposure prophylaxis, including the risk for HIV
transmission after the exposure, factors that may increase or
decrease this risk, and the limited knowledge regarding the
potential efficacy and toxicity of ZDV postexposure prophylaxis (9).
If a decision is made to use postexposure prophylaxis, it should be
initiated promptly (9). PHS is evaluating the implications of the
study summarized in this report and other available information in
assessing the possible need for revision of recommendations for
managing occupational exposure to HIV -- particularly regarding
postexposure use of antiretroviral agents.
References
1.Tokars JI,
Marcus R, Culver DH, et al. Surveillance of HIV infection and
zidovudine use among health care workers after occupational exposure
to HIV-infected blood. Ann Intern Med 1993;118:913-9.
2.Henderson
DK. HIV-1 in the health care setting. In: Principles and practice of
infectious diseases. 4th ed. Mandel GL, Bennett JE, Dolan R, eds.
New York: Churchill Livingstone, 1995:2632-56.
3.Ho DD,
Mougil T, Alam M. Quantitation of HIV type 1 in the blood of
infected persons. N Engl J Med1989;321:1621-5.
4.Richman DD,
Bozzette S. The impact of syncytium-inducing phenotype of human
immuno-deficiency virus on disease progression. J Infect Dis
1994;169:968-74.
5.Gerberding
JL. Management of occupational exposures to blood-borne viruses. N
Engl J Med 1995;332:444-51.
6.CDC.
Recommendations of the U.S. Public Health Service task force on the
use of zidovudine to reduce perinatal transmission of HIV. MMWR
1994;43(no. RR-11):1-20.
7.Ho DD. Time
to hit HIV, early and hard {Editorial}. N Engl J Med 1995;333:450-1.
8.Puro V,
Ippolito G, Guzzanti E, et al. Zidovudine prophylaxis after
accidental exposure to HIV: the Italian experience. AIDS
1992;6:963-9.
9.CDC. Public
Health Service statement on management of occupational exposure to
human immunodeficiency virus, including considerations regarding
zidovudine postexposure use. MMWR 1990;39(no. RR-1).
Single copies of
this report will be available free until December 21, 1996, from the
CDC National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD
20849-6003; telephone (800) 458-5231 or (301) 217-0023. **
Information on terminal illness in the source patient was missing
for 19% of case-HCWs and 48% of control-HCWs; information on visible
blood on device was missing for 3% of case-HCWs and 6% of control-HCWs.
By recoding the missing values to zero and including missingn value
indicator variables for these factors in the model, these HCWs were
retained in the analysis and their potential confounding influence
could be assessed. No significant interactions were found among the
risk factors in the model or between the risk factors and the
missing value indicators. When all HCWs with missing values for any
of the factors were excluded from the analysis, all of the factors
remained significant, with similar adjusted odds ratios but larger
confidence
intervals.
TABLE 1. Risk
factors for HIV infection in health-care workers after percutaneous exposure
to HIV-infected blood, based on a case-control study -- France,
United Kingdom, and United States, January 1988-August 1994
|
Risk
factor +) |
Adjusted
odds ratio * |
(95% CI |
|
Deep injury |
16.1 |
(6.144.6) |
|
Visible
blood on device |
5.2 |
(1.8-17.7)
|
|
Procedure
involving needle placed directly in a vein or artery |
5.1 |
(1.9-14.8) |
|
Terminal
illness in source patient |
6.4 |
(2.2-18.9) |
|
Postexposure
use of zidovudine |
0.2 |
(0.1-0.6) |
* All were
significant at p<0.01. + Confidence interval.="
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