Evidence that post-exposure treatment (PEP) with zidovudine is associated with a significant (79%) decrease in the risk of occupational transmission of HIV (usually after a needlestick accident) has propelled many to consider post-sexual exposure prevention of HIV through antiretroviral therapy. There are many factors differentiating transmission after a percutaneous needlestick exposure from transmission during sexual intercourse that need to be considered first. These include host factors (genetics, type of membrane exposed to HIV, presence of genital ulcers such as herpes or syphilis, frequency of exposure); viral factors (phenotype, size of inoculum, presence of resistance mutations); and environmental factors (timing of therapy, choice of drugs).

It is impossible to determine how effective or ineffective antiretroviral therapy is likely to be in a sexual transmission setting. The estimated average risk of transmission for one episode of unprotected receptive anal or vaginal intercourse ranges from 0.008 to 0.032 and 0.0005 to 0.0015, respectively, which is similar to the risk after a percutaneous exposure with a contaminated needle (0.3% or .003). No clinical trials with the available agents have been completed due to the difficulties in identifying potentially exposed individuals and treating them in both a uniform and timely manner. A feasibility study is about to be launched by HIVNET (the NIH-funded HIV Network for Prevention Trials) to assess the public health effectiveness of post-exposure prophylaxis in men who have sex with men. This study intends to randomize 750 men who have sex with men and are HIV-negative but report having engaged in anal sex within the previous two months.

The group will be divided into two arms: expedited access to PEP (usually through a 24-hour on-call mechanism to provide immediate counseling, testing and treatment) or usual care (referral to a list of local resources where PEP can be accessed in their community). The usual-care arm will obviously vary from site to site, depending on the local norm for treating sexual HIV exposure. In New York, the study will be conducted by the New York Blood Center, which is also conducting several vaccine feasibility studies with uninfected gay men and women. Other sites are in Boston, Washington, San Francisco and Seattle.

Steps to PEP

Many experts recommend administering antiretroviral therapy within 72 hours, and ideally within 36 hours, after unprotected anal or vaginal intercourse with a partner who is definitely or is likely to have HIV. Two recent analyses indicate that PEP interventions are probably cost-effective, as this cost is minimal compared to the lifetime cost of treating an HIV-infected individual.1, 2, 3

Assessment of the exposed person involves a detailed history of the event leading to the exposure, HIV antibody testing and counseling to ascertain the baseline HIV status and some evaluation of the partner's HIV status when possible. When treatment is decided upon, administration of the first dose follows extensive education regarding potential side effects, food restrictions, drug-drug interactions, and potential for triggering drug-resistant HIV through failure to strictly follow the dosing schedule. After PEP commences, close medical follow-up is necessary to ensure that the patient remains uninfected. All the while, counseling on safer sex and risk-reduction education should continue to prevent subsequent exposure-associated behaviors.

If the partner is found to be infected, HIV viral load testing and a complete treatment history are essential in order to decide what particular antiretroviral regimen to use. Most experts model the treatment regimen for PEP after that used for occupational exposures -- zidovudine and lamivudine for four weeks; with didanosine and stavudine as popular alternatives. Addition of a protease inhibitor should be considered if the source of the potential infection has advanced HIV disease, a high viral load (over 50,000 copies/ml) or has received one or both of the nucleoside analogs under consideration for the exposed person. If the partner has received multiple therapies, individualization of the regimen using new agents is advised.

The exposed person would also be assessed for the presence of sexually transmitted diseases, including Hepatitis A, B or C; syphilis; herpes; gonorrhea; chlamydia; HPV; and enteric parasites and offered treatment or vaccination if necessary.

The timing of initiation of antiretroviral therapy should be as soon as possible after the patient presents for evaluation, and the assessment, testing and counseling have been conducted. Animal studies indicated that post-exposure treatment after 72 hours have elapsed is unlikely to be effective.

In cases of sexual assault, PEP is also offered since perpetrators of rape are known to have a high incidence of HIV infection. Soon to be released criteria for administering PEP after rape have been devised by the New York State Department of Health and include: evidence of ejaculation; vaginal or anal penetration; tissue trauma; or presence of blood. Emergency contraception is usually offered to women, and routine empiric treatment for STDs and hepatitis B is offered to both men and women in addition to crisis intervention and psychological counseling.

Patients with repeated HIV exposures requesting PEP pose serious ethical dilemmas for health care providers. They should be counseled regarding how to avoid HIV exposure as well as the potential risk of infection despite PEP. Prophylaxis is unlikely to be 100% effective and poses the risk of resistant strains emerging and being transmitted. Referrals to ongoing interventions such as substance abuse treatment and counseling and self-help groups are a further possibility. The risk of using PEP to avoid safer-sex techniques, though perhaps real for a small minority, should not justify withholding treatment from any individual with a significant exposure.

Local Programs

The only experience to date on PEP is from San Francisco, through a project involving the University of California Center for AIDS Prevention and the San Francisco Department of Health. The project incorporates a 24-hour hotline and expedited access to a PEP regimen with close supervision and follow-up. For more information on the San Francisco PEP program, call 415/502-5PEP or visit its web site, http://hivinsite.ucsf.edu.

Unfortunately, other than the HIVNET study being conducted by the New York Blood Center, no organized program for PEP has arisen in New York City, and exposed patients often flounder in their search for a sympathetic provider who will assess them and provide rapid therapy. Most men who have sex with men do not seek PEP in Emergency Rooms except after sexual assaults, and the city health department at present has no program for PEP. Some private physicians provide PEP out of their offices to known patients. Others who are not convinced of the efficacy of the treatment or are concerned regarding the evolution of resistant strains are refraining from introducing PEP until a standard is set.

1. Li RW, Wong JB. New England Journal of Medicine. Aug. 14, 1997; 337(7):499-500.

2. Pinkerton SD et al. New England Journal of Medicine. Aug. 14, 1997; 337(7):500-1.

3. Katz MH et al. Annals of Internal Medicine. Feb. 15, 1998; 128(4):306-12.