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In theory, a person exposed to HIV during sexual assault or other
sexual activity can reduce the risk of infection by taking antiretroviral
drugs soon after exposure, a treatment known as postexposure prophylaxis.
Whether treatment should be offered routinely for sexual exposure,
however, is questionable. Safety and efficacy have not been adequately
studied and the treatment is expensive. Also, there are indications that
many patients will not complete the regimen.
Prophylactic treatment is often used by health care workers exposed to
HIV. It is also used to prevent perinatal transmission in newborn infants
of HIV-infected women. Treatment typically involves such drugs as
zidovudine, commonly known by its trade name, AZT.
The World Health Organization (WHO) does not provide guidance about
treatment following potential HIV exposure through sex. A 2000 meeting on
women and violence sponsored by WHO concluded that guidelines suitable for
developing-country situations should be written.
The U.S. Centers for Disease Control and Prevention (CDC) has said U.S.
physicians can consider HIV prophylactic treatment in case of unprotected
sex if there is a high risk of infection, but stops short of recommending
action in specific cases.1" The individual patient and
physician working together need to evaluate that person’s degree of
risk. If they decide together it is a high risk, then postexposure
prophylaxis is reasonable," says Dr. Lynn Paxton, who supervises
CDC’s work on this topic.
Regarding possible exposure to other sexually transmitted infections
(STIs), providers should consider presumptive treatment for bacterial STIs
and vaccination against possible hepatitis B exposure. Emergency
contraception should routinely be offered to victims of sexual assault to
help prevent pregnancy.
Degree of risk
Before offering HIV prophylaxis treatment after unprotected sex,
providers should consider the HIV status and risk-behavior history of the
reported source of contact. Unfortunately, the assailant’s HIV status is
rarely known in sexual assault cases. HIV status may or may not be known
in other types of unprotected sexual exposure.
The type of sexual exposure contributes to the degree of risk of HIV
transmission. Studies among HIV-discordant couples suggest that HIV
transmission by receptive anal intercourse occurs between 0.5 percent to 3
percent of the time. This is considerably higher than transmission by
unprotected penile-vaginal intercourse, estimated to be only about 0.1
percent (women, however, are at greater risk than men).2 By
contrast, infection from exposure to HIV-positive blood through the skin,
the typical risk among health care workers, is estimated to occur in 0.25
percent of the exposures.3
Recommendations on using HIV prophylaxis after sexual exposure are
based primarily on transmission risk. Dr. Michael Katz of the San
Francisco Department of Public Health and Dr. Julie Gerberding of the
University of California at San Francisco recommend prophylaxis after
unprotected anal or vaginal intercourse with a partner who is or is likely
to be HIV infected.4 Dr. Peter Lurie of the Center for AIDS
Prevention Studies, University of California at San Francisco, and
colleagues recommend HIV prophylaxis following unprotected anal
intercourse with someone known to have HIV infection or of unknown status
in a population with high HIV prevalence rates. "If the risk of
infection is moderate, in the range of 0.10 percent to 0.30 percent, we do
not believe the evidence currently warrants a recommendation" for
postexposure prophylaxis in all cases, say Dr. Lurie and colleagues.
However, people who have been exposed should be informed of the treatment,
they add.5
Drugs used for postexposure prophylaxis are often not available due to
costs, overall drug shortages, or hesitance to recommend a protocol
without definitive efficacy data. Even so, some international agencies
working in countries with high HIV-infection rates supply prophylaxis
drugs to their employees so that they can begin the treatment immediately
in the event of sexual assault.
Should HIV prophylaxis be used in the case of sporadic exposure during
consensual sex? Some experts are concerned that such prophylaxis may
discourage primary prevention, such as using condoms or reducing the
number of sex partners. Others speculate that the regimen could motivate
persons who have the highest risk to seek care. Because prophylaxis should
be used as soon as possible after exposure, some experts believe HIV
prevention messages should include information about HIV prophylaxis, such
as where it can be obtained.
Difficult regimen
The recommended postexposure prophylaxis regimen for possible HIV
infection is 28 days, which research has found to be difficult to
complete. Studies among health care workers who began treatment show
between one-third to about one-half of them discontinue treatment before
the recommended regimen is achieved.6 The reason most often
cited for discontinuation is side effects.
In a CDC prospective study of 449 people exposed to HIV during health
care work, 43 percent discontinued all drugs before the regimen was to be
completed and another 13 percent modified their regimen. More than half of
the 197 people who discontinued did so because of side effects. Most of
the rest of those who discontinued did so because they learned that their
exposure did not involve an HIV source. About three-fourths of the
patients reported some side effects, generally nausea, fatigue, malaise,
headache and vomiting.7
One of the few studies in developing countries on exposure to HIV by
health care workers surveyed 265 workers in the obstetrics and gynecology
department of a hospital in South Africa. Of those, 38 (13 percent) had
been exposed to HIV over one year. Of those 38, 35 took postexposure
prophylaxis. About half of them did not complete the regimen. Of those who
discontinued, 57 percent cited side effects as the reason.8
Little research exists on how well those possibly exposed to HIV during
unprotected sex will complete the regimen, although two studies suggest an
even lower completion rate. A sexual assault service working with a
Vancouver, Canada, hospital emergency department began offering HIV
prophylaxis in 1996 to women and children who came for treatment following
a sexual assault, the first such prophylaxis program in North America. Of
the 258 people who were seen by the service in the first 16 months, 71
accepted the offer of HIV prophylaxis. Only eight (11 percent) completed
the four-week regimen.
Victims of rape by an assailant known to be HIV infected or at high
risk for HIV infection were more likely to accept prophylaxis and to
complete the treatment than were other patients. Based on that finding,
the Canadian program changed its policy and now offers HIV prophylaxis
only to those at high risk of infection. "This change is likely to
improve compliance," the authors concluded. "It will also reduce
drug costs and will ease the burden on the physicians and nurses, as fewer
patients will need to be counseled about HIV prophylaxis."9
In a Boston hospital, 10 pediatric and adolescent patients were offered
HIV prophylaxis over a year’s time after sexual exposure or an
accidental needle stick. Eight started the treatment and two completed it.
Financial concerns, side effects, psychiatric and substance-abuse issues,
and parental involvement affected the degree of continuation.10
Generally, side effects from HIV prophylaxis are irritating but are not
a serious health threat, especially with zidovudine and lamivudine.
However, when nevirapine is used for HIV prophylaxis, adverse effects have
also been reported. In a British study, five of 41 patients using a
regimen containing nevirapine had serious adverse problems, including
hepatitis.11 In a report of similar cases, the CDC emphasized
that no serious toxicity from nevirapine has been reported when used in
regimens for mother-infant pairs or for treating HIV-infected persons.12
Another significant barrier to HIV prophylaxis is cost. In the United
States, medical practitioners estimate the cost at U.S. $1,100 to $1,600,
depending on whether a protease inhibitor is needed in the regimen.13
The Canadian program that began offering HIV prophylaxis in 1996 estimated
that the cost of preventing one case of HIV infection would be about U.S.
$70,000 (the cost of treating 140 patients, from which only one case of
HIV infection would be prevented).14
Effectiveness
While no study has examined the impact of treatment following potential
sexual exposure to HIV, related research suggests that it could be
effective in certain situations. For example, when health care workers
were exposed to HIV-infected blood through their skin, the chances of
infection were reduced by 81 percent if the worker took zidovudine after
exposure. The study involved more than 700 workers exposed to HIV from
1988 to 1994 and controlled for factors contributing to the risk of
transmission such as the quantity of the blood transferred in the
exposure.15 The CDC has issued recommendations for treatment of
health care workers exposed to HIV.16
Research has found that antiretroviral drugs have been effective in
preventing perinatal HIV transmission -- from a pregnant woman to her
newborn baby. In a prospective, randomized controlled trial, zidovudine
given to HIV-infected women during pregnancy and labor and to their
infants for six weeks postpartum reduced perinatal transmission by 67
percent compared to the control group.17 In a study in
Thailand, perinatal HIV transmission was reduced by 51 percent for women
treated from 36 weeks gestation until delivery.18
Treating HIV exposure with prophylactic drugs should be done promptly.
Presumably, the earlier the regimen is begun, the more effective it would
be. After exposure, the infection takes several days to become
established. Interventions may stop viral replication and allow the host
immune defenses to eliminate the virus. Research has shown that in the
case of infection by blood through needle-stick exposures, cells in the
skin can fight the infection with the proper chemical prophylaxis. Sexual
exposure to HIV through a mucosal surface is not completely analogous to
exposure through the skin, but it may involve similar responses, so
antiretroviral therapy may still stop infection by minimizing viral
replication.19
Preferably, therapy should be started within two hours after contact.
This is often impossible after sexual contact, however. The CDC says that
HIV prophylaxis is most effective when started within 24 hours after
exposure, but the amount of time during which treatment is effective has
not been studied in humans.
In addition to a 28-day regimen of zidovudine or lamivudine, treatment
with a more complicated series of drugs involving protease inhibitors
might be recommended if the exposure was to an HIV-infected person using a
particular drug treatment. Because of the regimen’s length, a person
potentially exposed to HIV infection several times a month would in
essence be using continuous prophylaxis. Thus, treatment is recommended
only for sporadic exposures.
Other STIs
Bacterial STIs are treatable. Ideally, a person seeking care after
unprotected sex would be tested for various bacterial infections and
treated if infected. The infection needs to be treated whether it resulted
from the immediate incident or from a previous exposure. However,
diagnosis is not possible in many settings that lack adequate laboratory
equipment and other resources.
Due to the obstacles of diagnosing and treating bacterial STIs
following unprotected sexual contact, many experts recommend postexposure
prophylaxis for bacterial STIs, especially in the case of sexual assault.
The CDC has developed guidelines for emergency STI treatment following
sexual assault. They include a combination of antibiotics designed to
function as presumptive treatment for gonorrhea, chlamydial infection,
bacterial vaginosis and trichomoniasis, commonly transmitted STIs.
The antibiotic regimen for these infections includes 125 mg of
ceftriaxone in a single intramuscular shot; 2 g of metronidazole in a
single oral dose; and either 1 g of azithromycin in a single oral dose or
100 mg of doxycycline orally twice a day for seven days.20
The CDC recommends using a vaccine against the viral STI hepatitis B
after sexual assault as a prophylaxis against possible infection. No
postexposure treatment exists for herpes simplex virus (HSV) or human
papilloma virus (HPV).
Where sexual violence frequently occurs, emergency STI treatment and
contraception have become part of some standard medical protocols. For
example, the United Nations Human Commission on Refugees recommends that
victims of sexual assault in refugee camps be provided emergency
contraception and treatment for bacterial STIs.
In Mexico, the Population Council, local nongovernmental agencies and
women’s advocacy groups have been working with hospitals, police,
psychological services and others who work with victims of rape to make
them and other women aware of emergency contraception. "We considered
adding a component to address postexposure prophylaxis for potential
STI/HIV exposure for victims of sexual assault," says the Population
Council’s Ricardo Vernon, who directed the project. "The simple
intervention of adding emergency contraception to the services provided
was already too controversial and complex to consider making the project
even more complex and expensive" by adding postexposure HIV
prophylaxis.
-- William R. Finger
References
- Centers for Disease Control and Prevention.
Management of possible sexual, injecting-drug-use, or other
nonoccupational exposure to HIV, including considerations related to
antiretroviral therapy. Public Health Service statement. MMWR
1998;47(RR-17):1-14.
- Lurie P, Miller S, Hecht F, et al. Post-exposure
prophylaxis after nonoccupational HIV exposure. JAMA
1998;280(20):1769-73; DeGruttola V, Seage GR, Mayere KH, et al.
Infectiousness of HIV between male homosexual partners. J Clin
Epidemiol 1989;42(9):849-56; Mastro TID. Probabilities of sexual
HIV-I transmission. AIDS 1996;10(suppl A):S75-S82.
- Ippolito G, Puro V, DeCarli G, et al. The risk of
occupational human immunodeficiency virus infection in health care
workers: Italian multicenter study. Arch Intern Med
1993;153(12):1451-58.
- Katz MH, Gerberding JL. The care of persons with
recent sexual exposure to HIV. Ann Intern Med
1998;128(4):306-12.
- Lurie, 1770.
- 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(12):913-19; Gounden YP, Moodley J. Exposure to
immunodeficiency virus among healthcare workers in South Africa.
Int J Gynaecol Obstet 2000;69(3):265-70.
- Wang SA, Panlilio AL, Doi PA, et al. Experience of
healthcare workers taking postexposure prophylaxis after occupational
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Control Hosp Epidemiol 2000;21(2):780-85.
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- Wiebe ER, Comay SE, McGregor M, et al. Offering HIV
prophylaxis to people who have been sexually assaulted: 16 months’
experience in a sexual assault service. CMAJ
2000;162(5):641-45.
- Babl FE, Cooper ER, Damon B, et al. HIV postexposure
prophylaxis for children and adolescents. Am J Emerg Med
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- Benn PD, Mercey DE, Brink N, et al. Prophylaxis with
a nevirapine-containing triple regimen after exposure to HIV-1. Lancet
2001;357(9257):687-88.
- Boxwell D, Haverkos H, Kukich S, et al. Serious
adverse events attributed to nevirapine regimens for postexposure
prophylaxis after HIV exposures -- worldwide, 1997-2000. MMWR
2001;49(51):1153-56.
- Katz.
- Wiebe.
- Cardo DM, Culver DH, Ciesielski CA, et al. A
case-control study of HIV seroconversion in health care workers after
percutaneous exposure. N Engl J Med 1997;337(21):1485-90.
- Centers for Disease Control and Prevention. Public
Health Service guidelines for the management of health care worker
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1998;47(RR-7):1-33.
- Sperling RS, Shapiro DE, Coombs RW, et al. Maternal
viral load, zidovudine treatment, and the risk of transmission of
human immunodeficiency virus type 1 from mother to infant. N Engl J
Med 1996;335(22):1621-29.
- Centers for Disease Control and Prevention.
Administration of zidovudine during late pregnancy and delivery to
prevent perinatal HIV transmission --Thailand 1996-1998. JAMA;1998;279(14):1061-62.
- Katz MH, Gerberding JL. Postexposure treatment of
people exposed to the human immunodeficiency virus through sexual
contact or injection-drug use. N Engl J Med
1997;336(15):1097-1100.
- Centers for Disease Control and Prevention. 1998
guidelines for treatment of sexually transmitted diseases. MMWR
1998;47(RR-1):109-11.
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