Pre-Exposure Prophylaxis (PrEP) for HIV

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What is PrEP?

  • Pre-exposure prophylaxis specifically for prevention of HIV 

  • Use of antiretroviral medication to individuals who do not have HIV, but are at risk for it.

    • Has been recommended by the CDC since 2012.

Why is PrEP needed?

  • HIV remains a significant public health problem in the USA and around the world.

    • 1.2 million persons have HIV as of 2021, with 87% aware of their diagnosis.

    • About 36,000 people receive HIV diagnosis per year.

      • Heterosexual contact accounts for ~22% of all HIV diagnoses.

      • Injection drug use accounts for ~7% of diagnoses.

    • The majority of new infections occur during reproductive years – about 20k of the 36k diagnoses per year are under the age of 35.

    • Persons of color and trans persons are disproportionately affected – and PrEP can be part of solution to fight inequity.

  • PrEP is effective, but underutilized:

    • 23% of persons who can benefit from PrEP are prescribed it – lots of room for improvement!

    • Discuss more on efficacy later.

    • As part of CDC’s End the HIV Epidemic initiative, they hope to increase PrEP coverage to 50% by 2025.

How effective is PrEP?

  • Very! Let’s quickly review some major trial data in heterosexual couples:

  • 2012: TDF2 Study Group, NEJM

    • RCT in Botswana randomizing to daily tenofovir-emtricitabine or placebo.

      • Two reverse transcriptase inhibitors

      • Brand names: Truvada, Descovy

    • 1219 men and women underwent randomization (45.7% women) and followed for a median of 1.1 years, but max 3.7 years.

    • 9 persons in treatment group and 24 persons in the placebo group became infected.

      • Estimated efficacy: 62.2%.

      • Higher rates of nausea/vomiting and dizziness in treatment group, but not long enough following to determine long-term safety data.

  • 2012: Partners PrEP Study Team, NEJM.

    • RCT in Kenya and Uganda for HIV-1 serodiscordant heterosexual couples, with three arms: daily tenofovir; daily combination tenofovir-emtricitabine; or placebo.

    • 4747 couples were followed.

      • In 38% of couples, the seronegative partner was female.

    • 17 infections in the tenofovir group; 13 infections in the combo drug group; and 52 infections in the placebo group.

      • Risk reduction of 67% with tenofovir alone, and 75% with the combo drug.

      • Rates of serious adverse events similar across groups.

  • 2012: FEM-PrEP Study Group, NEJM

    • RCT in multiple countries in Africa 

    • 2120 HIV-negative women to tenofovir-emtricitabine or placebo daily over two years.

    • 33 infections in combo drug group, 35 infections in placebo group.

      • No difference. Why?

        • Hypothesized that adherence was poor – while pill-count data suggested 88% of meds were taken, drug level testing suggested target plasma level was only identified in about 25% of participants tested.

        • Remember that a daily pill regimen can be challenging!

  • The CDC currently says that PrEP is:

    • 99% effective in reducing risk of HIV acquisition from sexual activity

    • 74% effective in reducing risk of HIV acquisition from IV drug use, when taken as prescribed.

CDC - PREP GUIDANCE

CDC - PREP GUIDANCE

Who should receive PrEP?

  • Patients at the highest risk are those who do not have HIV, but are known to have a male sexual partner that is infected with HIV (a “sero-discordant couple”). 

  • Other high-risk candidates where PrEP should be prescribed:

    • Engage in sexual activity within high HIV-prevalence area or social network, with:

      • Limited or no condom use

      • Diagnosis of other STIs

      • Use of IV drugs or alcohol dependence, or both

      • Incarceration

      • Exchange of sex for commodities, such as drugs, shelter, food, or money

  • Otherwise – if your patient is sexually active, with a partner with unknown HIV status or if they’ve had a bacterial STI in the last six months – it’s a good idea to at least discuss PrEP!

    • Currently, the CDC has a very simple flowsheet for determining if PrEP prescriptions are immediately appropriate. But discuss with your sexually active patients!

      • Including adolescents – ACOG Practice Advisory was a limited update to encourage PrEP discussion in this population.

      • PrEP is OK for anyone > 35 kg / 77 lbs.

How should I prescribe PrEP?

  • Preparation:

    • Determine baseline HIV status with testing – if positive, need treatment, not PrEP

      • Remember – if they’ve had a potential HIV exposure or acute HIV infection symptoms in prior 4 weeks, may need re-testing before determining if they are positive.

    • Determine STI status for other infections such as gonorrhea, chlamydia, and syphilis.

    • Assess hepatitis B status

      • Because emtricitabine and tenofovir can be used to treat hepatitis B, it’s important to test for this – stopping the medicine suddenly in an infected person can lead to rebound hepatitis.

        • If HBV is found or a patient is known to be HBV positive → counsel about this risk and monitor LFTs / HBV viral loads if they discontinue PrEP.

    • Assess kidney function:

      • Oral tenofovir can cause some minor renal damage, and rarely acute renal failure.

        • If CrCl > 60 mL/min, OK to proceed with oral PrEP.

        • If CrCl > 30 mL/min, OK to proceed with injectable PrEP (more on that later!)

    • Assess lipid profile:

      • Oral PrEP may cause changes in lipid profile – baseline assessment should be performed with triglycerides.

    • Same day prescribing of PrEP is OK for most patients as these labs are drawn – but do not prescribe in patients where testing can’t be obtained, patients with concerning history for acute HIV infection or renal disease/associated conditions, or without confirmed means of contact for discussing lab results.

  • Medications and Monitoring:

    • Daily Oral PrEP:

      • Truvada or Descovy (both are combinations of emtricitabine and tenofovir)

        • Truvada has been approved for heterosexual women, as well as MSM and trans women.

        • Descovy has been approved only for MSM and trans women (not for heterosexual women).

      • Patients should be monitored with:

        • HIV testing q3 months

        • Syphilis, gonorrhea, chlamydia testing approximatley every 6 months

        • Creatinine clearance estimate every 6 months

        • Lipid panel yearly

    • Injectable PrEP:

      • Relatively new (Dec. 2021): injectable cabotegravir (brand name: Apretude)

        • FDA approved for heterosexual women, MSM, and trans women at risk of HIV infection.

        • Injection schedule is 2 injections x 1 month apart, followed by q2 month injection.

      • Patients should be monitored with recommended surveillance STI testing:

        • HIV testing with every injection visit

        • Gonorrhea, chlamydia, syphilis on an approximately every 6 month basis.

    • 2-1-1 Oral PrEP

      • This is event-driven / “coitally-timed” PrEP.

        • This can be used by adult MSM, but is not recommended by the CDC and not FDA approved at this time. 

        • It hasn’t been studied in heterosexual women or trans patients.

What if my patient becomes pregnant on PrEP?

  • Women seeking to conceive and pregnant/breastfeeding women can use oral PrEP.

  • Important to understand in HIV is the “undetectable, untransmissible” or U/U principle:

    • Women whose sexual partner has a viral load <200 copies/mL have effectively no risk of sexual acquisition.

      • If partner remains on maximally effective antiretroviral therapy and has undetectable VL, PrEP may not provide additional protective benefit.

    • PrEP may be continued if desired, and a antiretroviral pregnancy registry is available to prospectively and anonymously submit information to obtain further data (www.apregistry.com) 


Further info

  • The CDC maintains a very extensive prescriber’s guide that is worth looking through to implement your own PrEP practice!

    • There is also a National Clinician Consultation Center at 855-448-7737 (855-HIV-PREP) that is available 9A to 8P ET on M-F to have clinician consultation for testing, prevention, treatment, and pre-exposure prophylaxis, and post-exposure prophylaxis resources.

  • The ACOG Practice Advisory also notes PrEP is widely covered with state Medicaid as preventive healthcare, and medication assistance is widely available – check out the end of the advisory for a list of resources.