Originally published 1/2020

Pre-exposure prophylaxis (PrEP) is a safe, effective, and autonomous method of HIV prevention offering the potential for enormous reduction in the risk of HIV transmission. PrEP is taken prior to potential HIV exposure and when used as directed PrEP is up to 99% effective in reducing sexual transmission of HIV. Unlike other HIV prevention strategies, HIV pharamcoprevention with PrEP offers individuals an autonomous option for HIV prevention prior to risk exposure or impairment due to substance use, avoiding the need for cooperation from sex partners or skills enactment while under the influence. However, PrEP has been under-marketed to and is underutilized by cisgender women. Although cisgender women represent more than half of new HIV cases worldwide and almost 1 in 5 cases in the United States, among cisgender women with indications for PrEP, only 10% utilize PrEP for HIV prevention. Multiple studies suggest that stigma surrounding PrEP use is a major barrier to uptake for this population. Perceived support from health care providers, social networks, the belief that PrEP is safe and effective, and overall positive attitudes towards PrEP are associated with intention to initiate PrEP.

The most recent guidelines from the Centers for Disease Control and Prevention (CDC) recommend that health care providers have open, non-judgmental conversations with all sexually active adults and adolescents, including pregnant people, about HIV prevention and PrEP. Additional strategies to prevent HIV infection beyond the scope of this Provider’s Guide include condom use, harm-reduction strategies for people who inject drugs, and antiretroviral therapy (ART) for people with HIV, commonly referred to as “treatment as prevention” (TasP) or “undetectable equals untransmittable” (U=U).

Who is PrEP for?

PrEP is for HIV-negative individuals who request it, regardless of their disclosed HIV risks or exposures, as well as anyone who discloses:

Anal or vaginal sex in the past 6 months and any one of the following:

• A sexual partner with known HIV (especially if viral loads are unknown or detectible)
• No or inconsistent condom use with a sexual partner with unknown HIV status
• A bacterial sexually transmitted infection (STI) in the past 6 months

Injection drug use and either:

• An injecting partner with known HIV or
• Shared injection equipment

Who should not use PrEP?

PrEP alone is insufficient treatment for HIV and may lead to antiretroviral resistance if an individual with HIV. Health care providers should not initiate or continue PrEP for anyone with known or suspected HIV. For people with signs or symptoms of acute HIV infection, such as flu-like symptoms, rash, pharyngitis, or lymphadenopathy and potential exposure to HIV in the last four weeks, acute HIV must be ruled out prior to initiating PrEP. For patients not on PrEP who present to care within 72 hours of a possible HIV exposure, offer nPEP instead. After a 28-day nPEP course followed by a negative HIV screening test, PrEP can be started immediately for anyone desiring continued protection. For more on nPEP, check out the Provider’s Guide.

Types of PrEP

There are currently two types of PrEP approved by the FDA, two daily, oral regimens and a new bi-monthly injection:

Oral PrEP

Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC, brand name Truvada)

• FDA approved for all individuals at risk of acquiring HIV.
• Clinical eligibility: HIV-negative by Ag/Ab test within one week of initiating, no signs or symptoms of acute HIV infection, eCrCl ≥60 ml/min, no contraindicated medications.
• Dose: Tenofovir Disoproxil Fumarate/Emtricitabine 300 mg/200 mg once daily.
• Most common side effects: headache, abdominal pain, weight loss.

Emtricitabine/Tenofovir Alafenamide (TAF/FTC, brand name Descovy)

• FDA approved for cisgender men and transgender women at risk of acquiring HIV through anal receptive sex. Not approved for cisgender women at risk from receptive vaginal sex or individuals at risk for HIV through injection drug use.
• Clinical eligibility: HIV-negative by Ag/Ab test within one week of initiating, no signs or symptoms of acute HIV infection, eCrCl ≥30 ml/min, no contraindicated medications.
• Dose: Emtricitabine/Tenofovir Alafenamide 25 mg/200 mg once daily.
• Most common side effect: diarrhea.

Counseling Tips for Oral PrEP:

• Side effects: In addition to the most common side effects, less than 10% of patients starting oral PrEP experience a “start-up syndrome” that typically resolves within a month. The most common symptoms are headache, nausea, and abdominal pain.
• When is it effective? Three weeks. It takes TDF/FTC seven days to reach protective levels in rectal tissue and 20 days in vaginal tissue. Data on TAF/FTC are not yet available.
• Daily dosing: PrEP is most effective when taken daily. However, PrEP leaves vaginal tissue faster than colorectal tissues, so daily adherence is especially crucial for patients at HIV risk through receptive vaginal sex.
• Missed doses: A missed dose should be taken as soon as it is remembered. If it is almost time for the next dose, then the missed dose should be skipped, and the regular dosing schedule continued. Double dosing is not recommended.
• Only HIV: PrEP only protects against HIV, not other STIs.
• Bone mineral density: TDF/FTC is associated with a 1% loss of bone mineral density (BMD), which has been found to stabilize or return to normal after discontinuation and does not suggest an increased risk of fracture. TAF/FTC is associated with a slight increase in BMD, but there is no difference in fracture risk when comparing the two medications. DEXA scans are not indicated or recommended prior to initiating PrEP.
• Renal function: TDF/FTC has been shown to cause a small decrease in renal function that is reversed when the medication is stopped. These changes have not been shown in patients taking TAF/FTC. Therefore, FDA approval for TDF/FTC includes patients with eCrCl ≥60 ml/min and for TAF/FTC for patient with eCrCl ≥30 ml/min.

Prescribing, Initial Labs, and Follow-up for Oral PrEP:

Patients on oral PrEP should be seen for follow-up every three months. These visits can be in-person or via telehealth, including by phone. Providers may schedule the first follow-up visit at a shorter interval, such as one month after initiating PrEP to repeat an HIV test due to the risk of undetected, acute infection at the first visit. This initial follow-up can also be used to screen for early side effects, discuss challenges with daily dosing, and provide additional education and counseling.

Lab testing during oral PrEP use includes blood tests for HIV, estimated creatinine clearance (eCRCl), Syphilis, Hepatitis B, Hepatitis C, and a lipid panel, and testing for gonorrhea and chlamydia at all anatomic sites of exposure. The CDC recommended testing frequency should be individualized based on characteristics and sexual practices, such as cisgender men and transgender women who have receptive anal sex, as well as in indication for PrEP, such as people who use injection drugs.

At each visit, patients should also be assessed for challenges with daily dosing and side effects. A team-based approach to care that includes a variety of provider types, such as physicians, PAs, nurses, pharmacists, and case managers all reinforcing medication instructions has been shown to improve correct and consistent use of PrEP. Reminder apps, support networks, and behavioral counseling can all provide additional support.

Injectable PrEP

Cabotegravir (CAB, brand name Apretude)

CAB was approved for PrEP by the FDA in December 2021, making it the newest form of PrEP currently available. It may be especially useful for patients with difficulty maintaining daily oral PrEP regimens or who prefer bi-monthly injections to daily pills, in particular for those with concerns about confidentiality. CAB is also a good PrEP option for patients with severe renal disease.

• FDA approved for all individuals at risk of acquiring HIV.
• Clinical eligibility: HIV-negative by RNA assay within one week of initiating, no signs or symptoms of acute HIV infection, and no contraindicated medications.
• Dose:
  
  Initiation injections: 2 doses of 600 mg IM, one month apart.
  

  Standard dosing: 600 mg IM every 2 months.
  

  Optional oral lead in: 30 mg cabotegravir daily for 4 weeks prior to first injection (can be beneficial to alleviate patient anxiety about side effects).
• Most common side effect: injection site reaction.

Counseling Tips for Injectable PrEP:

• Injection site reaction: Patients may experience an injection-site reaction, which typically lasts a few days. Pre-treatment with pain medication before or shortly after injection can help relieve the reaction. A warm compress for 15-20 minutes after injection and continued pain medication as needed can also be helpful.
• When is it effective? There are no data yet available on time from first CAB injection to maximal protection against HIV.
• Only HIV: PrEP only protects against HIV, not other STIs.

Prescribing, Initial Labs, & Follow-up for Injectable PrEP:

Patients using CAB should be seen for HIV testing one month after the first injection due to the risk of undetected, acute infection at the first visit, and then every two months in-person to receive follow-up CAB injections.

Lab testing during injection PrEP use includes blood tests for HIV and syphilis in addition to testing for gonorrhea and chlamydia at all anatomic sites of exposure. The CDC recommended testing frequency is based on individual characteristics, such as identifying as a transgender woman, as well as indication for PrEP, such as people who use injection drugs.

An HIV-1 RNA assay, the most sensitive test available, should be used to screen for HIV in patients using CAB, both at the initial visit and at each subsequent appointment. Injection of CAB is followed by a long duration of drug exposure making the exclusion of acute HIV prior to injection crucial. If a rapid HIV screening test is used for same-day PrEP prescribing, blood should also be collected for laboratory confirmation of HIV-negative status with an RNA assay.

Discontinuing PrEP

Patients may choose to discontinue PrEP for a variety of reasons, including lower HIV acquisition risk, intolerable side effects, inability to take medications daily when using oral PrEP, or difficulty maintaining regularly scheduled follow-up visits.

Oral PrEP: Ideally, individuals should continue oral PrEP for 28 days after their last exposure. Protection will decrease over seven to 10 days after stopping oral PrEP, so alternative methods of HIV prevention should be discussed, if indicated, as well as education about the availability of nPEP and how to access it within 72 hours of exposure. HBV-positive patients discontinuing oral PrEP should be monitored closely for a hepatitis flare, which has so far only been documented in patients with HIV discontinuing TDF-containing treatments.

Injectable PrEP: Given the lengthy duration of exposure to CAB following each injection, there will be a long “tail period” of gradually waning drug levels. If HIV infection is acquired during this tail period, there is a risk of drug resistance developing due to the continued low- level CAB concentrations. Alternative methods of HIV prevention should be discussed, including oral PrEP, as well as education about nPEP and how to access it within 72 hours of exposure. Patients should follow up quarterly for 12 months after discontinuing CAB, and HIV-1 RNA assays should be done at each of these visits.

Reinitiation of oral or injection PrEP requires repeating the baseline evaluation and laboratory tests based on the type of PrEP.

Paying For PrEP

PrEP is free under almost all insurance plans. For uninsured individuals or those in need of financial assistance, there are programs such as the U.S. Department of Health and Human Services’ ‘Ready, Set, PrEP’ program, and Gilead’s Medication Assistance Program for PrEP that can help.

Bottom Line

Health care providers can do our part in ending the HIV epidemic by routinely having open, non-judgmental conversations about HIV risk and PrEP with all HIV-negative patients at risk for HIV through sexual activity or injection drug use, regardless of age, sex, gender, or pregnancy status.

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