Published in the Bulletin of Experimental Treatments for AIDS October 1998 issue, by the San Francisco AIDS Foundation.

October 1998 Table of Contents

Main Page

beta@sfaf.org

Post-Exposure Prophylaxis: Still More Questions than Answers

Bruce Mirken

At the 12th World AIDS Conference, for the first time, an entire oral session at an international AIDS conference was devoted to post-exposure prophylaxis (PEP). PEP is the use of anti-HIV drug treatment as soon as possible after exposure to the virus in the hope of heading off infection (see Research Notes, BETA, June 1997). PEP was also the subject of numerous poster presentations at the conference.

PEP has been standard practice for healthcare workers since 1996, based on Centers for Disease Control and Prevention (CDC) data from a retrospective study showing a 79% lower rate of seroconversion among health care workers given AZT after a needlestick or other occupational exposure, compared to those who received no treatment.

Studies presented in Geneva included noteworthy information, but still left the big questions unanswered: does PEP work as well for sexual exposures to HIV as for occupational exposures? If so, how quickly must treatment be started in order to be effective? If PEP does work, is there an optimal regimen?

The majority of documented experience continues to involve healthcare workers. Adelisa Panlilio of the CDC reported on data collected by the agency’s National Surveillance System for Hospital Health Care Workers from June 1995 through December 1997. Of 58 healthcare workers who took PEP after occupational exposures to HIV, 28% took AZT alone, 34% took a 2-drug combination, 34% took a 3-drug combination, and 4% took four drugs. The latest U.S. Public Health Service (USPHS) guidelines recommend a four-week course of AZT/3TC for relatively mild or moderate HIV exposures, and adding indinavir (Crixivan) or nelfinavir (Viracept) only in cases where factors such as exposure to large amounts of blood or a source patient with a high viral load suggest a greater likelihood of transmission.

Most of those who took PEP reported side effects, including nausea and malaise. Twenty-one discontinued treatment prematurely and four modified their regimens (follow-up information was missing for 14 of the original 58). Of those who discontinued, 76% did so because of side effects. When broken down by occupation, technicians and nurses were more likely to complete therapy, while physicians were least likely to finish treatment.

Two trends surfaced in a number of presentations: a tendency toward more widespread use of 3-drug regimens than the USPHS guidelines recommend, and significant numbers of people stopping or modifying treatment due to side effects. Researchers from Yale University reported that of 49 healthcare workers taking PEP at two urban hospitals, most discontinued treatment when the source patient proved to be HIV negative. But of eight healthcare workers exposed to confirmed HIV positive source patients, only three completed the four-week regimen. Three discontinued due to gastrointestinal side effects and two due to "personal decision."

Low rates of follow-up plagued many PEP programs, making the collection of even preliminary efficacy data impossible. Phillipa Easterbrook of Chelsea and Westminster Hospital in London, one of the region’s major HIV treatment centers, described the hospital’s experience providing PEP for both occupational and sexual exposures from August 1996 to February 1998. The most common regimen was AZT/3TC/indinavir. Eight of 13 healthcare workers receiving PEP completed treatment, the rest stopping either because they perceived their risk of infection to be low or due to side effects. Only three of eight with a sexual exposure were known to have completed treatment, and only 26% of those exposed occupationally and 11% of those exposed sexually returned for all of their scheduled follow-up blood tests.

A PEP program for sexual assault victims at New York’s St. Vincent’s Hospital had even worse rates of follow-up. Of six people who received PEP (all but one receiving 3-drug regimens including a protease inhibitor), none returned for follow-up HIV testing, counseling, and medical evaluation. Only three of the 26 sexual assault victims who declined PEP returned for their follow-up visits, although a greater number returned for rape crisis counseling. "Our counselors feel that their clients have a lot of fear of knowing their HIV status or of seroconversion, and that may have been one of the reasons for the poor follow-up," Ramon Torres, MD, reported.

A survey of French physicians found some interesting -- and occasionally disturbing -- attitudes towards PEP. Twenty-six percent of the 678 physicians whose completed questionnaires could be evaluated reported receiving at least one request for PEP, and of those, treatment had actually been prescribed for 42%. Ninety-three percent of the doctors said they would be willing to prescribe PEP in cases involving condom breakage during male/male anal intercourse, but 65% indicated unwillingness to prescribe PEP in cases of unprotected male/male anal sex.

The San Francisco Experience

Two presentations focused on the well-publicized and somewhat controversial pilot program initiated last year by the San Francisco Department of Public Health and the University of California at San Francisco (UCSF) to provide PEP to those exposed to HIV through either sex or needle-sharing. The program, described as a "feasibility study," had evaluated 151 people as of May 31, 1998 -- about one patient per day since the program opened last winter, reported principal investigator James O. Kahn, MD. Projected enrollment is 500.

The program, put together with extensive input from the local AIDS activist community, aims to reach people within 72 hours of exposure to HIV. Those who elect to receive treatment are given a 7-day supply of drugs, then must come back for a follow-up visit to receive the next week’s medications. At the second follow-up visit they receive their final 14-day supply. The standard regimen offered is AZT/3TC, given in the form of Combivir, favored for its single-capsule, twice-daily dosing. Seventeen people received ddI/d4T, and just five received triple-combination regimens including a protease inhibitor.

One fear, that the program would be flooded by the "worried well," or people with very minor risk levels, appears not to have materialized. "Those with the highest risk of infection are those who seek to participate in our PEP project," Kahn noted. Of 136 people presenting with sexual exposures, 66 reported receptive anal intercourse, 23 insertive anal intercourse, 16 receptive vaginal intercourse, and 10 insertive vaginal intercourse, either with condom failure or without a condom. Two people reported receptive oral sex with ejaculation, and 19 had more than one type of exposure. Seventy-three people reported knowing that their partner was HIV-infected at the time of sexual contact. "I will admit we do have a very good telephone triage system," Kahn added. "If someone calls and says, ‘I just sat on a toilet seat. Can I come down and get PEP?’ we’ll triage them away from our project."

The San Francisco researchers reported higher completion rates and much better follow-up retention thus far than their counterparts from other locations. Of 140 people who had reached the 4-week evaluation point, 112 had completed their full course of therapy, though 14 of those took longer than the scheduled four weeks to finish their medication. Two people are known to have stopped treatment after finding out that their partner was in fact HIV negative. Twenty-six did not come in for their 4-week appointment (at the conclusion of their treatment), and further information on them had not yet been compiled.

So far no one receiving treatment in the San Francisco PEP program has seroconverted, and some press reports treated this news as an indication of efficacy. Kahn and colleagues were careful to state that it is way too early to draw such a conclusion, explaining that their study was not designed or powered to prove efficacy, but rather was intended to lay the groundwork for an efficacy study. This study was to determine if an appropriate population would enroll and return for follow-up visits, to develop the counseling and treatment protocols, etc. "We had no pretense that this was going to prove efficacy," Kahn said.

Asked why his project had so much better retention rates than others, Kahn credited the structure of the program, which has multiple return visits and a major counseling component built into the protocol. "[Participants] really are encouraged to adhere, their fears are addressed, and the problems and toxicities are managed," he noted.

It may also be that -- so far, at least -- the San Francisco PEP program has reached a particularly knowledgeable and motivated group. PEP has been extensively covered in the local gay press and heavily debated by the city’s AIDS activist community. Though Kahn did not present detailed data on the participants’ backgrounds and knowledge levels, the majority of initial participants have been white gay men, and may constitute a self-selected group more likely to follow through with treatment than the St. Vincent’s or Chelsea and Westminster participants.

Joshua Bamberger of the San Francisco Department of Public Health addressed the community concerns and controversies that arose after the PEP project was announced. Newspaper and television reports regularly referred to the program as a "morning-after pill," despite pleas from both researchers and community activists not to use such oversimplified and misleading terminology. "It’s not a morning-after pill. It doesn’t work that way," Bamberger emphasized. "It’s our responsibility as researchers to get out in the community and educate people."

In this atmosphere, some community groups worried that promotion of PEP would inadvertently send the message that safer sex is no longer essential, undermining prevention messages. Dealing with those concerns required working with the community. "The most important thing about the study is that we got buy-in from the community," Bamberger stated. "We asked the community to tell us how we can best tailor our regimens and tailor our program so that we can service the people who are affected by this virus."

One issue in these discussions was inclusion/exclusion criteria: what level of exposure would be enough to qualify a person for treatment? At the start there was some question about whether persons reporting only oral sex should be included, but after consultation with the study’s community advisory board it was decided to include those who had receptive oral sex with ejaculation.

Bamberger stressed that such community input is essential for those seeking to implement PEP programs. "It’s a give and take," he said. "Wherever you’re going home to, that’s the take-home message: you must include the community in all of your projects."

But Bamberger created a bit of controversy himself when he unveiled for the first time prototype posters for the San Francisco PEP study. He displayed one which said in large type, "OH SHIT! The condom broke." The ad’s text continued, "There’s a treatment that may prevent HIV infection, but you’ve only got 72 hours to start. Sooner is better. Call 502-2PEP. Call right away."

The posters -- which had not been previewed by the community advisory board -- drew considerable flak. Although Bamberger said that focus groups had approved the ads as "the most effective way to promote our study and not increase unsafe sex," several questioners expressed concern about the wording. "I write public health consumer brochures," one commented, "and consumers learn very quickly that when public health people use the word ‘may,’ they read it as ‘will.’ When they read ‘these drugs may cause side effects,’ they know that means they will cause side effects." He urged the researchers to find wording that is "a little more equivocal... That’s pretty strong language."

Bamberger acknowledged that the questioner had made "a very important point... How do you get people to come in within 72 hours, let them know that [the program] is there, but not falsely advertise something that isn’t proven?"

Less Concern?

The effects of PEP -- both in terms of treatment efficacy for people receiving therapy as well as the overall impact on community AIDS prevention efforts -- will not be understood for some time; in fact, treatment efficacy may never be known. A few presentations offered the first very preliminary hints about key issues.

A Swiss case report seemed to illustrate a case of PEP being given too late. A man presented with primary HIV infection 25 days after sexual contact with a prostitute. He reported having unprotected sex with his wife during the eight days immediately prior to his diagnosis, but began using condoms as soon as he was diagnosed. He was started on AZT/3TC/indinavir immediately, and ten days later his wife -- who at the time tested negative for HIV antibodies and had no detectable viremia -- began the same regimen.

The wife continued treatment for one month, but three weeks later returned with a viral load of 14,000 copies/mL. In a retrospective analysis of her stored blood samples, HIV RNA and integrated proviral DNA were intermittently detectable at low levels while she was on treatment. Genetic analysis of circulating viruses from both husband and wife showed a complete match in reverse transcriptase sequences, and the researchers concluded that "PEP, started 10-18 days after sexual exposure, failed to prevent HIV infection."

A few presentations suggested that optimism about PEP -- sometimes mingled with optimism about antiretroviral treatment in general -- may be leading a minority of gay men to take greater sexual risks. A poster presented by Seth Kalichman of the CDC described the results of anonymous questionnaires filled out by 327 gay men not in long-term monogamous relationships. Three percent said they had used PEP to prevent HIV infection and 26% indicated that they planned to do so. Those planning to use PEP, Kalichman reported, "were younger, less well educated, and more likely to use marijuana, nitrite inhalants, and cocaine in the last six months," and also "more likely to have practiced unprotected anal and oral intercourse as the receptive partner," and to have had receptive anal sex with multiple partners.

Kalichman drew no conclusions about whether this is simply a case of those most at risk considering PEP, or if knowledge of PEP might have led some to be less concerned about high-risk behavior. But a correlation between increased levels of unsafe behavior and optimism about PEP and about HIV treatment overall showed up in other studies as well.

Many of these surveys did not specifically ask about PEP, but one that did was conducted by James Dilley, MD, of UCSF, who reported on interviews with 93 men who sought anonymous HIV antibody testing and who reported at least one instance of unprotected anal intercourse with another man within the last year. Though Dilley reported that "improved antiretroviral treatment does not affect sexual decision-making among the majority of men who have sex with men," a minority of respondents did give answers suggesting that treatment developments had changed their attitudes about HIV and safer sex. Eighteen percent of the men surveyed who had had unprotected anal sex agreed with the statement, "I am much less concerned about becoming HIV positive." Of 47 who participated in a more in-depth counseling session focused on their attitudes at the time of their last unprotected anal intercourse, 17% said, "I’ll take new treatments to prevent my infection." Reports from other U.S. cities indicate similar patterns among gay/bisexual men.

While these relatively small and preliminary surveys certainly don’t constitute definitive information on the influence of PEP on HIV risk behavior, they prompted several researchers to emphasize the need to incorporate counseling, media outreach, and community information as part of any PEP program. As Bamberger put it, "We need to move ahead, but we need to move ahead responsibly."

  Page last updated 6 October 1998

About AIDS | Treatment | Prevention | Policy | About SFAF | Take Action | Donate
Español | Search | Site Map | Feedback | Email Updates | Home (sfaf.org)