Stopping HIV Infection with PEP

by Enid Vázquez

After three days, he quit. He said, “If I had to go on HIV medication, I would kill myself.”

He was exaggerating, of course, but his point remains: this therapy ain’t candy. Besides, who wants to take medications they don’t have to take? And not one time, but for a whole month? Plus, even though the research results to date look very good, the treatment may or may not work.

That just needs to be clear when looking at the exciting potential for using medications to prevent HIV infection after exposure through sex or needle use.

(The use of HIV drugs for occupational exposure among healthcare workers, emergency workers and others has long been established, and has a set of guidelines. There are several differences between occupational and non-occupational exposure.)

It looks like people can take this route to avoid infection, but there’s a price to pay—if only the approximate $1,000 that insurance probably won’t cover for this experimental treatment. (Although the drugs themselves are not experimental, using them to prevent HIV is.) Fortunately, the very low rate of transmission seen in research to date is very encouraging.

In January, the U.S. Department of Health and Human Services (DHHS) issued recommendations for the use of HIV drugs to prevent infection after community-based exposure (primarily sexual contact or sharing needles during drug use). This article briefly reviews those recommendations and caveats.

Words, words, words

· “prophylaxis” is something used for prevention

· PEP stands for “post-exposure prophylaxis,” or a preventative measure used after exposure

· nPEP is for “non-occupational PEP”—or PEP in the community (not work) setting

Prevention first

First of all, practicing safer sex techniques and not sharing needles is the front-line of defense against HIV infection.

Counseling, please

Second of all, counseling is considered an essential aspect of nPEP. From the report: “At follow-up visits, clinicians should assess their patients’ needs for behavioral intervention, education, and services. This assessment should include frank, non-judgmental questions about sexual behaviors, alcohol use, and illicit drug use. Clinicians should help patients identify on-going risk issues and develop plans for improving their use of protective behaviors.”

Availability

Doctors not experienced with the use of these drugs should obtain the advice of a specialist when prescribing nPEP, or when the source of the potential infection indicates that he or she has HIV drug resistance. Healthcare providers (only) can try the University of California—San Francisco HIV Warmline for information, 1-800-933-3413. They can also contact the National Clinicians’ Post-Exposure Prophylaxis Hotline at 1-888-448-4911, 24/7. Remember, the nearest pharmacy may not stock the medicine.

Drug resistance

If HIV infection occurs, there is the possibility that the patient’s newly acquired virus can develop resistance to the drugs he or she took during nPEP.

Prison

The DHHS report notes that, “Administrators and health-care providers working in correctional settings should develop and implement systems to make HIV education and risk-reduction counseling, nPEP, voluntary HIV testing, and HIV care confidentially available to inmates. Such programs will allow inmates to benefit from nPEP when indicated, facilitate treatment services for those with drug addiction, and assist in the identification and treatment of sexual assault survivors.”

Rape

Sexual assault can have characteristics that increase the risk of HIV, such as trauma to the lining of the genitals. HIV test results must be separated from a sexual assault report, because they might end up exposed in court. Reimbursement might be available for the use of PEP after sexual assault. PEP has long been available in emergency rooms for rape survivors. The report also notes that, “Sexual assault is not uncommon among men. In one series from an emergency department, 5% of reported rapes involved men sexually assaulted by men. Males accounted for 11.6% of rapes reported among persons age 12 or older who responded to the National Crime Victimization Survey in 1999.”

The therapy There is no "morning after" pill for HIV. The drug treatment used to prevent an HIV infection after sex or needle use consists of several pills taken every day for a month. According to recent guidelines from the U.S. Department of Health and Human Services (DHHS): 1. Therapy should be started as soon as possible after exposure to HIV, no more than 72 hours later (three days)* 2. It continues for 28 days 3. Due to the potential for emotional upset at the time of therapy, an initial prescription for only three to five days worth of medicine helps patients come back when they're better able to understand the healthcare worker's explanation of how the therapy works, as well as provide an opportunity to discuss and treat any side effects that may have occurred 4. Treatment is recommended when the source is known to be HIV-positive and the exposure event was high risk 5. If a positive source is willing to see the medical provider, a history of that person's medication and viral load can be taken to help determine the treatment to take; the clinician might consider drawing blood for viral load and drug resistance testing 6. If the HIV status of the source is unknown and the person shows up for treatment more than 72 hours after exposure, treatment is neither recommended nor not recommended—the decision is left to the doctor and the patient 7. If it's past 72 hours, but a high-risk exposure, the doctor may choose to start treatment if he or she believes that the potential benefit outweighs the possible side effects 8. Patients should have potentially serious side effects explained to them, and should have access to "on-going encouragement and consultation by phone or office visit"** 9. Patients should be told about signs and symptoms associated with a recent HIV infection, especially fever and rash; where there is evidence of early infection, it might be prudent to continue the therapy beyond 28 days 10. Liver function and kidney function should be monitored, as well as hematologic parameters 11. Unless they're receiving this therapy as part of a research study, patients might have to pay for treatment out of their own pocket [Editor's note: HIV drugs are very expensive] Other considerations: · The patient may already have a prior infection and not know it; it's recommended that a rapid HIV test (with results within an hour) be conducted at screening · Risk for transmission might be especially great if the exposure was from someone who had been recently infected with HIV, when the level of HIV in the blood and semen might be particularly high · HIV infections after only one reported exposure have been seen in nPEP programs [as they have with all HIV reporting—infections are known to occur after only one encounter] · Prevention for other sexually transmitted infections (STIs) should be considered, as well as hepatitis B vaccination for people who are not immune to it; also, the presence of another STI can increase the risk of getting HIV · Emergency contraception should be considered for women exposed to semen * "The sooner nPEP is administered after exposure, the more likely it is to interrupt transmission."—DHHS ** Reports from nPEP research, including the healthcare setting, often note a high rate of stopping therapy because of side effects

Injection drug users

According to DHHS, “In judging whether exposures are isolated, episodic, or on-going, clinicians should consider that persons who continue to engage in risk behaviors (e.g., commercial sex workers or users of illicit drugs) might be practicing risk reduction (e.g., using condoms with every client, not sharing syringes, and using a new sterile syringe for each injection). Therefore, a high-risk exposure might represent an exceptional occurrence for such persons despite their on-going risk behavior.” Healthcare workers should find out if injection drug users are interested in substance abuse treatment and make referrals to treatment when it is desired. They should check for knowledge of safe injection and sex practices. Also, referrals should be made to local syringe exchanges.

Pregnancy

Sustiva cannot be used by pregnant women or women hoping to become pregnant. A combination of Zerit with Videx also cannot be taken during pregnancy.

Children

The American Academy of Pediatrics has issued nPEP guidelines for children. Visit www.aap.org. The DHHS pediatric HIV treatment guidelines discuss the use of AIDS medications in children.

Cities and states

The San Francisco County Health Department, the New York State AIDS Institute, the Massachusetts Department of Public Health, the Rhode Island Department of Health and the California State Office of AIDS have issued policies or advisories for nPEP use. Some of these concentrate on survivors of sexual assault.

Increasing risk?

The DHHS summarizes the research to date, which shows that the availability of nPEP does not necessarily lead to increased risk behavior—one of the biggest concerns, if not the biggest, of both providers and the public.

The meds

The report directs people to a separate document for a list of drug combinations that can be used; see table at right. The list is from the DHHS guidelines for HIV treatment in adults and adolescents, consisting of drugs recommended for first-time therapy.

The nPEP report, however, points out that there’s not yet enough evidence to indicate that a three-drug combination recommended for people with HIV would be more effective than a two-drug regimen for the use of prevention. The report states that a two-drug combination can be considered if there’s concern about toxicity or adherence (sticking to the drug schedule and requirements).

Two-drug combos are included as an option in the healthcare PEP guidelines from the U.S. Public Health Service (which can be ordered from the same place as the nPEP report, see below). The occupational guidelines discuss the use of two drugs because of the potential for added toxicity if a third drug is used. Two drugs may be preferable for an exposure that is not high-risk.

According to the nPEP report, “Regardless of the regimen chosen, the exposed person should be counseled about the potential associated side effects and adverse events that require immediate medical attention.” Medications to treat side effects, such as anti-diarrhea and anti-vomiting drugs, might improve adherence.

Drugs to use

There are two different levels of drugs—preferred and alternative—given in the treatment guidelines for first-time therapy. Two drugs lead the list of preferred combinations, Sustiva and Kaletra (see generic names below). Viramune, although used in HIV treatment, cannot be taken as PEP. British nPEP guidelines recommend against Sustiva; visit www.bashh.org. See possible side effects under “Comments” below. Note: Although it is not stated, five of the drugs listed can be taken in a separate combination. Epivir and Retrovir are available as one pill, called Combivir. Epivir and Ziagen are available together as Epzicom. Emtriva and Viread are also available as one pill, called Truvada.

Obtaining the report

For a free copy of “Antiretroviral Postexposure Prophylaxis in Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States,” as well as “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents,” call 1-800-HIV-0440 (448-0440). Write AIDSinfo, P.O. Box 6303, Rockville, MD 20849-6303 or visit www.aidsinfo.nih.gov.

Comments

The nPEP report, by its official and scientific nature, must be cautious in its statements. In the real world, there are other considerations that can be taken into account, proof or no proof. Here then, are some things to consider.

Can you take a whole month off from work? It would probably help a lot. Side effects can be nasty.

Remember, it is highly unlikely that one person can use nPEP over and over! This is not the answer to prevention. It is a back-up plan when all else fails.

Just because nPEP recommendations exist doesn’t mean that people can show up in any doctor’s office and get a prescription. Nor is it available upon demand.

It’s not an easy task to decide to prescribe nPEP in the first place and it’s not easy to pick a drug combination in the second place. If you are at high risk, think of whom you can go to if you experience a high-risk exposure. The National AIDS Hotline may be able to refer you to the nearest HIV medical provider; call 1-800-342-AIDS (2437).

In some areas, emergency rooms may be the best bet for obtaining nPEP, if only for a few days while you look for a doctor. Emergency room staff should already be familiar with the use of PEP for rape victims as well as hospital staff, and have some of the medications on hand. Even if you have a local nPEP program, it may be closed over the weekend, and the emergency room can carry you over until the program clinic opens.

People who take the same combination as that taken by the person who exposed them to HIV, or drugs to which that source is already resistant, may—possibly—be taking a regimen that is less effective for them. Remember too that if infection takes place, the newly infected person runs a risk of developing drug resistance to the medications he or she used during nPEP.

The predominant virus seen in North America and Europe, HIV-1, is harder to transmit from women to men, but very easy to transmit from a man to a woman. The virus seen predominantly in other parts of the world, HIV-2, seems to be almost equally transmitted from women to men as from men to women. Moreover, people in the United States who are infected with HIV-2 may test negative on all but one HIV test given here. That test is the OraQuick Advanced. (All positive test results must be followed with a confirmatory test, which picks up both HIV-1 and HIV-2.)

What about the “superbug”? Picking up a virus that has resistance to HIV medications has been seen for years. In other words, people with a new HIV infection may have gotten a virus that doesn’t respond to one or more HIV drugs or even entire drug classes. Getting an HIV resistance test is recommended at the time of HIV diagnosis under DHHS treatment guidelines, even if not beginning treatment. Drug resistant transmission varies around the country, usually no more than 25% for one drug or one drug class. In other words, the likelihood that someone is getting infected with drug-resistant virus ranges from around 10% to around 25%.

On the other hand, for people who remain uninfected, having taken PEP will not affect their drug options should HIV infection occur later on. Drug resistance develops in the virus, not the person’s body.

Note: Pharmacist and Positively Aware contributor Tony Hosey, Pharm.D., of the HIV specialty pharmacy StatScript, wrote a comprehensive report on nPEP in the March/April 2005 issue. His report included coverage of the research supporting the use of nPEP, the political climate surrounding the therapy and the difference between PEP and nPEP.

He says, “If someone had one option to minimize the chances of seroconversion, by taking meds for one month, would they go for it? The drugs are not easy, and sometimes the side effects can be a lot, but would it be worth it to help minimize the risks of seroconversion? With true counseling techniques, most of the side effects can be overcome or minimized. HIV-positive people have been doing it to keep themselves alive and healthy, so it can be done.”