Is HIV Treatment Practical after Exposure?

The degree of risk from exposure is among factors in determining whether treatment should be available.

Network: 2001, Vol. 21, No. 1

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

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14. Wiebe.
15. 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.
16. Centers for Disease Control and Prevention. Public Health Service guidelines for the management of health care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR 1998;47(RR-7):1-33.
17. 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.
18. 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.
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20. 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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