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Post-Sexual Exposure Prophylaxis: A Roundtable Discussion

Prophylaxis with combination antiretroviral therapy after significant needlestick and other exposures is now commonplace in the healthcare setting. Increasingly, providers are being asked whether similar steps should be taken after high-risk sexual exposures. To help our readers follow the complexities of this rapidly evolving issue, we are pleased to present the following roundtable discussion. Our discussants are three experts actively involved in the area: Mitchell Katz and Julie Gerberding have been instrumental in creating a demonstration project of post-sexual exposure prophylaxis in San Francisco. Steve Boswell is Executive Director of Boston's Fenway Community Health Clinic, long known for providing primary care to an urban population including many young gay men. Readers may also want to consult ACC's August 1997 issue, featuring an article by Johanna Daily on the related topic of prophylaxis following occupational exposure. -- Deborah Cotton

1. Pragmatically, how do you determine if a sexual exposure confers sufficient risk to warrant postexposure prophylaxis (PEP)?

Drs. Katz and Gerberding: The quantitative risk associated with a specific sexual exposure to HIV is hard to measure. The available data suggest that the probability of transmission through a single episode of rectal or vaginal intercourse with someone known to be HIV infected is within the same order of magnitude as that associated with occupational needle punctures (0.003). Probability of transmission is highest for unprotected receptive anal intercourse (0.008 to 0.032). Unprotected receptive vaginal intercourse (0.0005 to 0.0015) is riskier than insertive vaginal intercourse (0.0003 to 0.0009).

Per-episode risk estimates for other types of sexual exposure to HIV are not available. There are no published estimates of the per-contact risk of HIV transmission with insertive anal or oral intercourse, but both of these behaviors transmit HIV. Even for the sexual behaviors for which we have per-contact risk estimates, a number of other factors influence transmission (e.g., trauma, inflammatory or ulcerative genital lesions). Moreover, in some cases (e.g., sexual assault, anonymous sexual contacts), it may be unknown whether the partner is HIV infected.

Given the tremendous uncertainty in the estimates of risk of HIV transmission with a single exposure, we recommend offering PEP to people who have had unprotected anal or vaginal intercourse with a person known to be HIV infected or in a group at risk for HIV, such as an injection drug user. We also recommend offering treatment to people who have had unprotected receptive oral intercourse with ejaculation. Condom breakage and slippage would be considered unprotected sex.

Dr. Boswell: In our clinic we have defined three categories of risk we believe are sufficient to warrant consideration of PEP:

1. Unprotected anal or vaginal intercourse (receptive or insertive) with a known HIV-positive partner or a partner of unknown serostatus, or protected intercourse with condom breakage;

2. Exposure of mucosal surfaces to blood or infected body fluids from a known HIV-positive person or a person of unknown serostatus; and

3. Oral exposure to ejaculate or cervicovaginal secretions of a known HIV-positive partner or a partner of unknown serostatus. Oral exposure to a penis without ejaculate is of sufficiently low risk to make the potential benefit of PEP negligible.

We have intentionally made these categories broad in order to capture as much information as possible about the types of exposure for which PEP is sought. This information will be used in our research project, funded by the Massachusetts Department of Public Health and Glaxo-Wellcome.

The timing of the risk behavior is also an important factor in assessing the appropriateness of PEP. Animal models of parenteral exposure to HIV suggest that delaying therapy by more than 24 to 36 hours dramatically decreases the likelihood of effectiveness. However, there are currently few data and virtually no human data upon which to base a precise cutoff. Participants in our study are eligible to receive PEP if no more than 72 hours have elapsed between the time of exposure and the initiation of antiretroviral therapy. This time frame was chosen in order to determine the best balance between maximal effectiveness and the practical aspects of delivering complicated therapies to exposed individuals.

Other factors may also be important in stratifying risk of transmission. These include

1. The stage of HIV infection in the source partner (the more advanced the disease in this individual, the greater the risk of transmission);

2. An elevated viral load in the source patient;

3. The presence of menstrual blood in a female source partner during sex;

4. A history of sexually transmitted disease (especially genital ulcers) in either partner; and

5. An uncircumcized insertive male partner, which may enhance the risk of acquisition and transmission.

In general, these factors are less influential than the risk behavior and the interval between contact and therapy.

2. In your experience, what are the minimal services required to effectively deliver post-sexual exposure prophylaxis? What would be the optimal services to put in place?

Drs. Katz and Gerberding: The ingredients of an effective program include

1. Assessment of HIV risk;

2. HIV testing and STD evaluation;

3. Expertise on antiretroviral regimens;

4. Enhanced prevention counseling and/or referral to ongoing prevention resources; and

5. Easy, round-the-clock access to services.

A thorough assessment of HIV risk enables the client to make an informed decision on whether to take antiretroviral medicines. Clinicians should ask about the specific sexual acts, the HIV status and risk factors of the client and partner, and any available health information about the partner (e.g., antiretroviral drug history, recent viral load or CD4 cell count data). The time of the most recent sexual act is important because PEP is much less likely to be effective if administered more than 72 hours after exposure.

Baseline HIV testing should be available because many people at risk for HIV have not been recently tested. Clinicians should not wait for the results of HIV testing to initiate PEP. But patients who are found to be HIV-infected will need ongoing treatment, rather than the 28-day course recommended for PEP. Patients who have had unprotected sex will also need evaluation for sexually transmitted diseases and pregnancy (for women).

With the rapidly expanding repertoire of antiretroviral agents, expertise on drug regimens is important. This is especially true for patients exposed to someone who has been on multiple antiretroviral drugs in the past. Patients also need to be advised on the side effects associated with the chosen PEP regimen.

PEP programs are most likely to be effective for both the individual and the community when they emphasize preventing future HIV exposures. The treatment encounter could help motivate behavioral change in exposed people and decrease their long-term risk. Ideally, care providers possess the skills and knowledge to provide enhanced prevention counseling. At the very least, community resources that can provide these services on a referral basis should be integrated into the program. Program implementation must be accompanied by effective public health messages that clearly communicate the primary role of safer sex and safer injection drug use in HIV prevention. Messages should emphasize that PEP is only a back-up measure when safer sexual practices fail.

Patients should have access to treatment as soon as possible after exposure. Ideally, services should be available 24 hours a day. If this is not feasible, then at least a telephone triage system ("hotline") should be available.

Dr. Boswell: A site must provide access to a health care provider within 72 hours of the exposure -- preferably much sooner. The provider should be trained in HIV counseling and antiretroviral therapy. Ready access to essential laboratory tests, including direct measurement of HIV (p24Ag, HIV bDNA, HIV PCR), is important. Mental health counseling is often needed. Finally, providers should be familiar with the care of victims of sexual assault, including knowledge of sexual assault examinations and evidence collection. The ability to perform appropriate STD screening is essential.

All services should be rendered in a confidential manner and without regard to ability to pay. Currently, most health insurers will not pay for PEP following sexual exposures. Since few exposed individuals can afford the cost of the medications, laboratory testing, and multiple visits that PEP requires, the site must be able to absorb these costs.

3. What is the best setting for post-sexual exposure prophylaxis -- one central facility or multiple facilities of different structure?

Drs. Katz and Gerberding: The optimal venue for services will vary depending on the patient clientele. Patients are apt to seek PEP where they know or believe they will receive respectful and confidential care. Many cannot or will not travel to distant treatment sites. From a purely economic or logistic standpoint it may be most efficient to centralize services, but this is not likely to be optimal from the patient's perspective. In practice, services will be needed wherever the patient presents to obtain them.

In most locales, patients will seek PEP in emergency departments or urgent care clinics, where the expertise needed to make complex decisions about antiretroviral treatment regimens and to provide effective behavioral counseling is usually not immediately available. This situation is similar to that encountered in occupational exposure management.

One possible compromise between the centralized and decentralized approaches is to initiate care in a network of sites where clients are likely to present (e.g., emergency departments, drop-in clinics) but establish a dedicated clinic for ongoing follow-up. An initial treatment protocol provided by the dedicated clinic and supplemented by telephone access to expert clinicians might allow for decentralized access while maintaining high-quality services.

STD clinics may be particularly appropriate sites to provide PEP since they routinely provide HIV counseling and testing. They perform follow-up care and are usually known in the community for the confidential nature and low cost of their services.

Dr. Boswell: A central facility has the advantage of economies of scale. Such a setup also facilitates systematic information collection, which is necessary in order to answer many questions about post-sexual exposure treatment: What are the best-tolerated drugs? How long should they be given? Is post-sexual exposure prophylaxis effective?

The drawbacks to a central facility may be patient inconvenience and less personalized care. Centralizing facilities means that some individuals seeking PEP will have to travel farther to avail themselves of the service, and care will most likely be given by providers who do not have an established relationship with the patient. These factors may make some individuals less likely seek the service.

On balance, I believe that having several centralized facilities is the best approach, at least initially. It is essential to gather information about this service, and a centralized approach is the most effective structure for this. Once we have sufficient information to warrant continuation and expansion of these programs, a less centralized approach might be considered.

4. What is the total cost of providing post-sexual exposure prophylaxis? Who should bear this cost?

Drs. Katz and Gerberding: The total cost of offering prophylaxis includes the cost of procuring the drugs, charges for laboratory tests needed to monitor treatment safety and HIV status, and the personnel and facility costs needed to implement and manage the program. Drug treatment costs vary depending on the regimen. The average wholesale cost for a 4-week course of AZT and lamivudine is approximately $500. Including a protease inhibitor (indinavir or nelfinavir) adds approximately $500 to $600. The medical visits and laboratory studies necessary to assess drug side effects add about another $600.

Two cost-effectiveness analyses indicate that the cost per year of life saved with PEP is within the range of other commonly recommended interventions, at least for those sexual practices most likely to transmit HIV. However, these analyses assume that PEP following sexual exposure is as effective as treatment following a needlestick. Since the true efficacy of PEP following sexual exposure has not yet been determined, medical insurers may refuse to cover it. Moreover, the people at greatest risk for HIV exposures (young gay men, injection drug users, poor people of color) are unlikely to have private health insurance. For these reasons, the major responsibility for funding PEP programs will probably fall to the public health system. If the programs are successful in promoting behavior change and creating a net reduction in new HIV infections, then the money will be well spent.

Dr. Boswell: Our costs are similar to those cited by Drs. Katz and Gerberding: a four-week combination regimen such as AZT (600 mg/day in two to three divided doses) and lamivudine (300 mg/day in two divided doses) costs approximately $480, and adding a protease inhibitor increases the cost by $420 to $530. In short, medication costs alone for four weeks of PEP can be approximately $500 to $1000, depending on the regimen used.

Laboratory monitoring may add another $500, for viral antigen testing (bDNA, PCR, or pAg), ELISA, Western blot, chemistry, and CBC, and office visits another $300 or more. Our total costs for providing post-sexual exposure prophylaxis are $1300 to $1800 per treatment. These costs vary significantly, since treatment side effects and the emotional stress of PEP are quite variable.

It is my belief that the resources for post-sexual exposure prophylaxis should be provided by government and industry, since these programs most appropriately fall under the rubric of research. If the data that come from these projects add further credibility to the provision of post-sexual exposure prophylaxis, the cost of these programs should be borne by third-party payors. This will require preemptive legislative action to ensure that payors do not discriminate against those who seek the service.

5. Will clients request post-sexual exposure prophylaxis repeatedly? If so, how should such requests be handled?

Drs. Katz and Gerberding: Undoubtedly, some clients will request more than one course of post-sexual exposure prophylaxis. This is not a surprise. It is rare in the field of prevention for a single intervention to result in permanent behavioral change for everyone. This is especially true of complex behaviors like sexual relations.

Rather than choosing a uniform cut-off for the number of courses of PEP that will be provided, clinicians should determine the reasons for repeated exposures and work with people to prevent future exposures. Some patients will request a second course of prophylaxis because of a second condom breakage or relapse to unsafe behavior. In these circumstances, a second course with enhanced prevention intervention (e.g., reviewing how to put on a condom, additional counseling about the triggers for unsafe sex) may be very appropriate. At the other extreme, some clients may request prophylaxis as a way of maintaining or increasing high-risk behavior. Since prophylaxis is unlikely to be 100% effective, increases in risky sexual behavior due to clients' perception that prophylaxis will keep them from becoming infected would actually increase the chance of HIV infection. Clinicians are not obligated to provide harmful therapy. People who repeatedly put themselves at risk for HIV clearly need help. However, more intensive prevention counseling is more likely to be effective than repeated courses of antiretroviral therapy.

Dr. Boswell: We have had over 30 significant inquiries about post-sexual exposure prophylaxis, and not one of these has been a repeat case. In our experience, when people learn what is required in PEP, especially if they have already taken the regimen once, they come to understand that it is not a walk in the park. We provide counseling designed to decrease the likelihood of a second incident. This important aspect of PEP may allow us to target the highest risk individuals for behavioral intervention.

Should repeated requests occur, each would be assessed on an individual basis. There are no easy answers to the repeated request problem. Aggressive behavioral intervention should be a significant aspect of the response, whether PEP is provided or not.

— Deborah Cotton, MD, Moderator

Dr. Katz is Interim Director of Public Health for the City and County of San Francisco. Dr. Gerberding is Associate Professor of Medicine at UCSF and Director of the Epidemiology and Prevention Interventions Center at San Francisco General Hospital. Dr. Boswell is Executive Director of the Fenway Community Health Center and an investigator in HIVNET, an NIH-sponsored HIV vaccine testing network. • National Hotline for Advice on Occupational PEP -- The National Clinician's Post Exposure Prophylaxis Hotline (PEPLine), from San Francisco General Hospital, offers advice on treating healthcare workers accidentally exposed to HIV and hepatitis. Open 24 hours a day, seven days a week, PEPLine may be reached by calling 1-888-448-4911.

Published in AIDS Clinical Care February 1, 1998

Citation(s):

Katz MH and 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 1097-1100.

• Original article (Subscription may be required)
• Medline abstract (Free)

Katz MH, Gerberding JL. The care of persons with recent sexual exposure to HIV. Ann Intern Med 1998 128 306-312.

• Original article (Subscription may be required)
• Medline abstract (Free)

Li RW and Wong JB. Postexposure treatment of people exposed to the human immunodeficiency virus through sexual contact or injection-drug use. N Engl J Med 1997 337 Letter 500-501.

Pinkerton SD, et al. Is postexposure prophylaxis for sexual or injection-associated exposure to HIV cost-effective? N Engl J Med 1997 337 Letter 500-501.