Clinical Considerations

Before we begin, do you prescribe PrEP for HIV?

  1. No
  2. Yes
  3. No, but I would if I were more knowledgeable about it

Analysis

Section 1, Graphic 1. Pie chart of answers at CAFP symposium.

As you can see, 40% of participants at the CAFP symposium would prescribe PrEP if they knew more about it. This learning activity is designed to help you achieve that goal.

SECTION 1: HIV/SEXUAL DISEASE RISK ASSESSMENT

Ronald H. Goldschmidt, MD

In 1981, the Centers for Disease Control and Prevention (CDC) published the first report identifying individuals with what came to be known as acquired immunodeficiency syndrome (AIDS).[CDC 1981] Since then, scientists and clinicians have made great strides in understanding, treating, and preventing HIV disease. So, why is there now, in 2017, a renewed interest in preventing HIV disease? Despite testing, counseling, condoms, education, and other preventive measures, there are still about 40,000 cases of new HIV diagnosed in the United States every year.[HIV in the US (CDC) 2016] Most of these transmissions are preventable.

First-line prevention strategies involve not only safer sexual and drug use practices but also antiretroviral (ARV) drug therapy in 3 distinct ways: (1) treatment as prevention (treating persons with HIV to decrease the possibility that they can transmit HIV); (2) post-exposure prophylaxis (PEP); and (3) pre-exposure prophylaxis (PrEP) to HIV-uninfected persons at risk.

Treatment as Prevention. Effective ARV treatment markedly reduces the amount of HIV present in body fluids (eg, semen, vaginal, and anorectal secretions) and blood (as measured by HIV viral load). Fluids from persons with very low or undetectable HIV virus levels are markedly less likely to transmit HIV to uninfected persons.  A study published in 2011 provided convincing evidence for the success of this preventive measure, called “treatment as prevention.” This randomized trial involved serodiscordant couples—1 partner was positive for HIV and had CD4 counts between 350 and 550 cells/mm3, whereas the other partner was HIV negative. Half of the infected partners received immediate ARV therapy, and the other half received delayed therapy based on CD4 cell count decreases or the appearance of HIV-related symptoms. Of the subsequent 28 linked transmissions, only 1 occurred in the early therapy group. Early ARV treatment resulted in both personal and public health benefits, including a dramatic and significant reduction in the rate of sexual transmission.[Cohen 2011]

Case #1

Post-exposure Prophylaxis. The medical assistant in your office gave an influenza vaccination to JT, a 35-year-old male patient who came in for an urgent care visit. She reports she stuck herself with the needle after the injection.

The patient then sees you and says he is here because he had insertive and receptive rectal intercourse with a man he met at a bar 18 hours ago. He does not know if the person is HIV-positive and has no way to get in touch with him.

HIV exposure and risk of transmission

For an infectious agent found in blood, any percutaneous exposure (one that breaks the skin barrier) can potentially lead to disease transmission. [USPHS Occupational Exposure 2013] Contact with mucous membranes, which are absorptive, or non-intact skin, such as an open wound, also poses a risk. Skin forms an effective barrier against HIV transmission unless there is a portal of entry. Rough cuticles are not usually considered a portal of entry because a protective buildup of cells and tissue occurs rapidly following small breaks in the skin.

Fast Facts

Skin forms an effective barrier against HIV transmission unless there is a portal of entry

The following table lists fluids that are potentially infectious for HIV, particularly blood and semen. Other fluids, such as feces and saliva, are not considered potentially infectious, UNLESS they are visibly bloody.[USPHS Occupational Exposure 2013]

Section 1, Graphic 2. Body fluids potentially involved in HIV transmission.[USPHS Occupational Exposure 2013]

Clinical Considerations

What is the HIV transmission risk per exposure for an occupational needle stick (from a source known to be HIV infected)?

  1. 0.23%
  2. 2.3%
  3. 23%
  4. >23%

Analysis

The answer is A, 0.23%. The risk of HIV transmission varies depending on the route of transmission as well as other factors, such as viral load. For an occupational needle stick from a source known to be infected with HIV, the risk of HIV transmission is 2.3 per 1000 exposures, or 0.23%.[Patel 2014; CDC PEP Guidelines, 2016]

Section 1, Graphic 3. HIV transmission rates by route of transmission.[Patel 2014; CDC PEP Guidelines, 2016]

When considering the next steps to take in managing a potential exposure to HIV, the most important test is a rapid HIV test of the source person, if available.[USPHS Occupational Exposure 2013] In this case scenario, the initial source (the person your patient met at the bar) cannot be found for testing. However, the patient himself should be offered PEP, as long as he is HIV negative. Therefore, he should have a baseline HIV test. What about the medical assistant who sustained the needlestick? If JT, the patient who came in for the flu shot, is HIV negative, than she does not need PEP.

The key rapid diagnostic test is called a 4th generation test; it is a combination test for HIV antibodies and the HIV p24 antigen [CDC Laboratory Testing, 2014] The availability of this test has helped decrease the time required to detect HIV infection (Section 1, Graphic 4). Earlier, 3rd-generation tests detected only HIV antibodies and not the p24 antigen. Because it takes some time for the body to generate anti-HIV antibodies after first exposure, there is an interval where patients are potentially infectious even though they test negative for HIV antibodies. This is referred to as the seroconversion “window period.” The 3rd-generation tests required at least 3 weeks to detect infection. The p24 antigen appears at an earlier time point during HIV infection, so 4th-generation tests can detect infection within 13 to 42 days after exposure for most people.[CDC Laboratory testing, 2014; CDC Window period, 2017] HIV RNA, which can be detected by nucleic acid tests, is the earliest marker of infection. However, nucleic acid tests are expensive, and it may take many days for results to become available. They are used primarily for high-risk exposures or possible exposures in patients with early symptoms of HIV infection.[CDC Laboratory Testing, 2014]

Section 1, Graphic 4. Appearance of laboratory markers during HIV infection. Adapted from CDC Laboratory, 2014.

Almost all people seroconvert (produce antibodies to HIV) within 3 months,[CDC Laboratory Testing, 2014] and over half display the signs and symptoms of acute HIV syndrome—fever, fatigue, myalgia, and rash—during this time.[CDC PEP, 2016] These symptoms can easily be overlooked or attributed to other illnesses, so clinicians should be sure to review sexual histories in patients with unknown viral illnesses (Section 1, Graphic 5).

Section 1, Graphic 5. Signs and symptoms of acute primary HIV syndrome.[CDC PEP, 2016]

In addition to a 4th generation HIV test, patients who may have been exposed to HIV should receive testing for hepatitis B virus (HBV), hepatitis C virus (HCV), and sexually transmitted infections (STI).[CDC PEP 2016] For patients who test HIV negative at baseline, repeat HIV testing should occur at 4 to 6 weeks and at 3 months after exposure to confirm that no HIV infection has occurred.[CDC PEP 2016]

To date, there are no known cases of occupational transmission during the window period between initial infection and seroconversion,[USPHS Occupational Exposure 2013] but this may reflect the rarity of occupational exposure events. This window period is known to be associated with high infectivity for non-occupational exposures. It has been estimated that the rate of sexual transmission is 26 times higher during early HIV infection compared with established infection. Moreover, up to 50% of all new HIV transmissions occur during the acute infection period.[CDC PEP 2016]

The PEP Decision: To Offer PEP or NOT

The decision to offer PEP must often be made based on incomplete information about the source’s infection status. In most cases, treatment should not be delayed pending results from HIV tests.[CDC PEP 2016] If the source has been clearly identified and a rapid test is possible, then it is acceptable to wait 3 or 4 hours for the results of the rapid test before deciding on PEP. However, it is not acceptable to wait 2 or 3 days for the results of HIV testing.

For patients who may have been exposed to HIV, our default approach is to initiate PEP as soon as possible. Many patients find it reassuring to engage in proactive treatment, and medication can be stopped subsequently if test results indicate that the source was not infected. However, ultimately, the final decision to initiate PEP rests with the patient.

The CDC guidelines for PEP encourage initiation of ARV therapy as soon as possible following exposure or possible exposure to HIV and always within 72 hours of exposure.[CDC PEP, 2016] There is currently no evidence that PEP works when initiated 72 hours or more after exposure.[CDC PEP 2016] Treatment should be continued for 28 days.[CDC PEP 2016]

The CDC-recommended PEP treatment regimen consists of triple-drug therapy (Section 1, Graphic 6).[CDC PEP 2016] The preferred regimen should be modified for individuals with renal dysfunction. These drug regimens have excellent tolerability and proven potency in HIV infection. Drug interactions are generally not a concern, but patients should be screened for renal and hepatic disease. All of the agents in the recommended regimens are given orally once a day (with the exception of raltegravir, which is taken twice daily). Clinicians should follow up with patients given PEP 3 to 4 days after treatment initiation. Counseling and support should be offered, and patients should be asked about adherence, side effects, and symptoms. HIV testing should be repeated at 4 to 6 weeks, and again at 12 weeks. [CDC PEP 2016]

Section 1, Graphic 6. Preferred and alternative antiretroviral medication 28-day regimens for PEP.[CDC PEP, 2016]

Case #1, Continued—From PEP to PrEP

The patient, JT, decides to initiate PEP. His HIV antibody tests at 12 weeks show no signs of infection. JT returns 6 months later. He has been given PEP from the local hospital emergency department on 3 other occasions since you first saw him, and they have recommended that he come back to see you for follow-up. After putting up with your tedious lecture on safe sex, which you’ve been practicing for so many years, and your positive feedback regarding his having obtained PEP from the emergency department when needed, he asks you if there’s anything else he needs to know to prevent HIV infection. You initiate a discussion of HIV pre-exposure prophylaxis (PrEP).