Physician Guide to HIV Pre-Exposure Prophylaxis (PrEP)

Indications for starting PrEP

PrEP is indicated in adults and adolescents over 35 kg,¹Preventing New HIV Infections [Internet]. CDC.gov. 2020 [cited 15 February 2020]. Available from: https://www.cdc.gov/hiv/guidelines/preventing.html with normal kidney function, who are at increased risk for contracting HIV.

The following factors are associated with increased risk of HIV transmission and are potential indications for initiating PrEP:

• Condomless sex with partners:
  • Of unknown HIV status.
  • With unsuppressed HIV, on treatment.
  • With untreated HIV.
  • Who have multiple or anonymous additional sexual partners.
  • Who use IV drugs.
• A bacterial sexually transmitted infection (STI) diagnosis within the past 6 months.²Final Update Summary: Prevention of Human Immunodeficiency Virus (HIV) Infection: Preexposure Prophylaxis – US Preventive Services Task Force [Internet]. USPreventiveServicesTaskForce.org. 2020 [cited 20 February 2020]. Available from: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure-prophylaxis
• Use of mood-altering drugs during sex. Taking drugs during sex may lead to riskier behavior including less consistent condom use.³Halkitis P, Levy M, Solomon T. Temporal relations between methamphetamine use and HIV seroconversion in gay, bisexual, and other men who have sex with men. Journal of Health Psychology. 2014;21(1):93-99.
• IV drug use, especially when sharing equipment such as needles.⁴Smith D, Pan Y, Rose C, Pals S, Mehta S, Kirk G et al. A Brief Screening Tool to Assess the Risk of Contracting HIV Infection Among Active Injection Drug Users. Journal of Addiction Medicine. 2015;9(3):226-232.
• Self-identification as being at increased risk for contracting HIV.

Patients who engage in lower risk behaviors–including consistent condom use, exclusively oral sex, and no IV drug use–generally do not need to be started on PrEP.

Contraindications to starting PrEP

Contraindications to starting PrEP include:

• HIV-positive patients. Individuals with positive or unknown HIV status must not be started on PrEP.⁵Marrazzo J, del Rio C, Holtgrave D, Cohen M, Kalichman S, Mayer K et al. HIV Prevention in Clinical Care Settings. JAMA. 2014;312(4):390. The use of PrEP in HIV infected individuals has been associated with development of drug resistance in the virus.⁶Gibas K, van den Berg P, Powell V, Krakower D. Drug Resistance During HIV Pre-Exposure Prophylaxis. Drugs. 2019;79(6):609-619.
• Drug-resistant HIV exposure. Patients with known exposure to drug-resistant HIV should receive post-exposure prophylaxis (PEP), as the medications used for PrEP are not effective against drug-resistant HIV strains.
• Renal impairment. TDF-FTC has the potential to be nephrotoxic, while TAF-FTC has a more benign renal profile. Impaired estimated glomerular filtration rate (eGFR) is a relative contraindication to starting PrEP, per the following:
  • TDF-FTC generally should not be started in patients with an eGFR < 60 mL/min/1.73 m².⁷Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional
  • TAF-FTC generally should not be started in patients with an eGFR < 30 mL/min/1.73 m².⁸Descovy FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/560/descovy/0/professional
• Receptive vaginal sex. TAF-FTC is not indicated for PrEP in patients who have receptive vaginal sex.⁹Descovy FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/560/descovy/0/professional In this situation, TDF-FTC should be prescribed if otherwise indicated.

Initial patient evaluation and history

Before prescribing PrEP, the provider should elicit a thorough patient history focused on evaluating the risk of HIV infection in addition to other important considerations. Patients should be evaluated for:

• Signs and symptoms of recent HIV infection, including flu- or mono-like illness with or without rash, oropharyngeal candidiasis, or mucocutaneous ulcers.
• High-risk encounters within the past 72 hours requiring the use of PEP prior to starting PrEP.
• Use of medications affecting renal function, including nonsteroidal antiinflammatory drugs (NSAIDs), especially when considering TDF-FTC for PrEP.¹⁰Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional
• Known hepatitis B virus (HBV) infection. TDF-FTC is indicated for HIV prophylaxis as well as treatment of HBV infection, as TDF is FDA approved to treat HBV.¹¹Tenofovir Disoproxil Fumarate FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/290/tenofovir-disoproxil-fumarate/26/professional Patients with HBV should therefore be continued on TDF or TDF-FTC for HBV treatment even if PrEP is no longer indicated, as severe HBV exacerbation is possible upon discontinuation of treatment.¹²Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional If a patient with HBV infection stops taking TDF-FTC, hepatic function should be closely monitored for several months, and alternative HBV therapy should be considered.
• Known hepatitis C virus (HCV) infection. Several treatments for HCV, including ledipasvir-sofosbuvir, are known to cause increased levels of TDF and may precipitate tenofovir toxicity if used in combination.¹³Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional
• Pregnancy or potential to become pregnant.
• Willingness and ability to adhere to a daily medication regimen.

Initial laboratory testing

In addition to a thorough history, the provider should order the following tests before prescribing PrEP:

• Fourth generation antigen-antibody HIV test. A third generation immunoglobulin (Ig)M/IgG antibody HIV test is an acceptable alternative if a fourth generation test is unavailable and suspicion for recent HIV infection is low.
• HIV ribonucleic acid (RNA) viral load test if the patient has had:
  • A possible HIV exposure in past 4 weeks–including condomless anal or vaginal sex, or sharing IV drug needles–regardless of symptoms.
  • Signs or symptoms of acute HIV infection in the past 6 weeks.
• Complete metabolic panel, including renal profile with eGFR and hepatic panel.
• HBV serologies, including hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs).
• Chlamydia and gonorrhea screen by nucleic acid amplification testing (NAAT).
• Syphilis screen per the provider’s institutional protocol.
• Pregnancy test in patients able to become pregnant.
• Dual energy X-ray absorptiometry (DXA) scan in patients at risk for osteopenia or osteoporosis. TDF-FTC can reduce bone mineral density.¹⁴Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional

Note: PrEP may be started while test results are pending unless the patient has signs or symptoms of acute HIV infection, had an exposure in the previous 72 hours requiring PEP, or has a history of renal impairment.

Ongoing monitoring and laboratory testing

PrEP should ideally be started on the same day as the initial clinic visit in patients without known HIV infection, signs or symptoms of acute HIV infection, need for post-exposure prophylaxis (PEP), or significant renal impairment.

After starting PrEP, patients should be seen at 1 month, 3 months, and every 3 months thereafter. PrEP should be prescribed for a maximum 90-day supply.

At every visit

• Perform HIV testing with a fourth generation antibody-antigen HIV test and an HIV RNA viral load test in patients who present with signs and symptoms of acute HIV infection.
• Assess for pregnancy in those patients who are able to become pregnant.
• Discuss the following topics with patients (additional topics are covered in patient counseling):
  • Address barriers to PrEP access and adherence.
  • Recommend personalized HIV risk reduction techniques.
  • Inquire about medication side effects.
  • Provide recommendations for free or inexpensive condoms and drug injection equipment (if applicable).

1 month after beginning PrEP

• Perform HIV testing in patients who report possible HIV exposure in the 30 days before beginning PrEP.

Every 3 months

• Obtain a basic metabolic panel with eGFR 3 months after beginning PrEP.
• Perform HIV testing with a fourth generation antibody-antigen HIV test.¹⁵Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional
• Screen for gonorrhea, chlamydia, and syphilis, even in patients without symptoms. Testing frequency may be adjusted based on risk.

Every 6 months

• Obtain a basic metabolic panel with eGFR. This may be done more frequently for patients at increased risk of renal dysfunction. Providers should discontinue TDF-FTC for PrEP in patients who have an eGFR of < 50 mL/min/1.73 m² and consider switching to TAF-FTC if otherwise indicated.

Annually

• Perform HCV testing in at-risk patients.

Monitoring of serum drug concentration is not indicated with either form of PrEP.

Some medications used for HCV treatment, including ledipasvir-sofosbuvir, can elevate TDF levels. Patients using these medications in combination should be monitored for tenofovir toxicity.¹⁶Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional

Patient counseling and risk reduction

Medication is one component of a comprehensive HIV prevention program. Further risk reduction is achieved through open and non-judgmental dialogue with patients regarding the following topics:

• Daily PrEP use. TDF-FTC and TAF-FTC are both once-per-day tablets that can be taken with or without food. Patients should be counseled about the importance of taking PrEP every day for optimal protection from HIV.
• Consistent and proper condom use. Patients should receive counseling that PrEP does not provide 100% protection from HIV infection and does not protect against other STIs. Consistent condom use is recommended while on PrEP to protect from STI transmission. For patients who choose not to use condoms, it is important to counsel patients that PrEP achieves maximum protection from HIV transmission after 7 days when engaging in receptive anal sex and after 21 days when engaging in receptive vaginal sex.¹⁷PrEP [Internet]. CDC.gov. 2020 [cited 16 February 2020]. Available from: https://www.cdc.gov/hiv/basics/prep.html Patients should use condoms or abstain from sex during this initial period before PrEP is maximally effective.
• Safe IV drug use. Patients who use IV drugs should receive counseling about safe injection practices to reduce the risk of other viral and bacterial infections.
• PrEP use in pregnancy. PrEP with TDF-FTC should not be withheld from pregnant patients or patients attempting to conceive. TDF and FTC are both pregnancy category B. TAF safety in pregnancy is unknown.
• PrEP use while breastfeeding. TDF and FTC are present in breast milk;¹⁸Tenofovir Disoproxil Fumarate FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/290/tenofovir-disoproxil-fumarate/26/professional^,19Emtricitabine FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/208/emtricitabine/23/professional it is unknown whether TAF is present in breast milk. With breastfeeding patients, counseling should include a discussion of the risks and benefits of PrEP to the breastfed child. The risks of PrEP to breastfeeding children are currently unknown.

Side effects of PrEP

• TDF-FTC may reduce kidney function and can lead to osteopenia, osteoporosis, or osteomalacia.²⁰Truvada FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/406/truvada/8/professional
• TAF-FTC can cause weight gain and dyslipidemia.²¹Descovy FDA Label [Internet]. AIDSinfo. 2020 [cited 16 February 2020]. Available from: https://aidsinfo.nih.gov/drugs/560/descovy/0/professional