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Episode #14 – Fresh stART: PrEP School

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Summary

Dr. Meredith Clement schools us in everything you need to know about HIV pre-exposure prophylaxis (PrEP)!

Credits

Host: Sara Dong

Guest: Meredith Clement

Writing/Consult Notes: Elise Merchant, Sara Dong

Producing/Editing/Cover Art: Sara Dong

Infographics: Elise Merchant

Our Guests

Meredith Clement, MD

Twitter

Meredith joined the Louisiana State University (LSU) faculty in 2018 following the completion of her Internal Medicine and Infectious Diseases training at Duke University. Her academic interest lies in the prevention of HIV and sexually transmitted infections (STIs) in vulnerable populations, including racial/ethnic and gender minority populations in the South.  She has a particular focus on how to reduce the burden of HIV infection by maximizing the impact of pre-exposure prophylaxis (PrEP). She has been involved in PrEP related research since 2014 and is currently studying the intersection of STIs and PrEP use through a NIAID K23 career development award.

Elise Merchant, MD

Twitter

Dr. Elise Merchant is now an ID attending at Tufts.  She completed my adult Infectious Diseases Fellow at Beth Israel Deaconess Medical Center. She grew up in Montana, but moved to New England to study Anthropology and Biology at Brown University, then attended medical school at Tufts University School of Medicine. She stayed on at Tufts Medical Center for Internal Medicine residency and a chief resident year, before moving across town to BIDMC for fellowship, where she completed additional training in the Clinician Educator Track.

Her interests include medical education, HIV, and sexually transmitted infections. She also love board games, fantasy novels, dabbling in art, consuming caffeine, and hanging out with my cat, Ollivander.

Culture

Meredith loves living in and exploring New Orleans!

Consult Notes

Consult Q

Use of pre-exposure prophylaxis (PrEP)

One-liner

25 year old cis-gender man who would like to initiate HIV pre-exposure prophylaxis (PrEP)

Key Points

Jump to:

PrEP Resources
HIV Risk Assessment
Candidacy for PrEP
PrEP Efficacy
PrEP Safety
TDF/FTC vs. TAF/FTC
Other PrEP regimens
Investigational PrEP regimens
Monitoring
PrEP + PWID
TasP

As Meredith mentioned, “it’s a disservice to the patient to not take a sexual history.”  We referred back to episode 5 with Dr. Anu Hazra for a few reminders on taking a comprehensive sexual history and other learning points.  Find the Consult Notes here: https://febrilepodcast.com/episode-5-adventures-from-sti-clinic/

We’ll be discussing HIV pre-exposure prophylaxis, or PrEP!  Here are some resources before we get started.

Who is most at risk for HIV infection?  How should you think about risk stratification in an individual who comes to see you in clinic?

Unfortunately there are still many new diagnoses of HIV, in the United States and worldwide.  According to the CDC:

  • Estimated 1.2 million people living with HIV in the US today. Approximately 14% are unaware of their diagnosis
  • Estimated 38,400 new HIV infections occurred in 2019
  •  

Groups at highest risk:

  • Rates of new infection are highest in MSM
      • MSM of color disproportionately affected: Black > Latino > White. 
      • Black individuals account for 42% of new HIV diagnoses, although only make up 13% of the population.
  • After MSM, the next highest risk group is Black heterosexual women, followed by then people who use drugs.
  • The highest risk age group for new diagnoses was 25-44 years old. 
  • The risk of HIV is highest in the South > NE > West > MW, concentrated in certain counties 
      • Meredith mentioned the Ending the HIV Epidemic initiative, which focuses additional resources and expertise to expand HIV prevention and treatment activities to 57 priority jurisdictions which you can find here.

Check out more info/statistics here: Centers for Disease Control and Prevention. Estimated HIV Incidence and Prevalence in the United States, 2015–2019. Vol 26.; 2021. 

 

The United States Preventative Service Task Force (USPSTF) and CDC also have guidance on considering an individual patient’s history and behaviors to help assess individual risk level.

  • Need to consider individual history and behaviors as well as HIV prevalence in the community
      • Not all MSM and transgender women who have sex with men are high risk for HIV acquisition. If they are in a mutually monogamous relationship with a partner who has tested negative recently (or since they’ve been monogamous), they are not high risk.
  • According to the USPSTF, cis-gender MSM are considered high risk if they are:
      • Sexually active AND
          • Either are in sexual relationship with someone living with HIV OR
          • Inconsistently use condoms during anal sex OR
          • Have a history of an STI (syphilis, gonorrhea or chlamydia) within the past 6 months (USPSTF)
      • The most recent CDC guidelines from 2017 identify the same risk factors for cis-gender MSM, as well as commercial sex work and high number of sexual partners.
      • The criteria to be considered high risk if this patient were a woman are similar:
          • Sex partner with HIV
          • Inconsistent condom use during sex with a partner whose HIV status is unknown and is high risk (injects drugs or also has sex with men)
          • Gonorrhea or syphilis within the past 6 months
      • Commercial sex workers as well as transgender women and men are recommended to be evaluated using the same criteria.

The first step is evaluating whether your patient would be a good candidate for PrEP.

  • Obtain detailed sexual and social history to determine patient’s risk of HIV acquisition (see above section)
  • Evaluate for other conditions that may place them at risk of adverse effects related to PrEP or other considerations, such as
      • Reduced kidney function
      • Osteoporosis
      • Weight gain and dyslipidemia
      • Hep B virus infection
      • Pregnancy
  • Assess for possible barriers for daily medication use and willingness to adhere to PrEP

Your patient is interested in PrEP but would like to hear a little more information about how effective it is before committing.

Whether or not to take PrEP is an individual decision, and is definitely influenced by patient preferences. We do know that there is good evidence for PrEP, and the USPSTF gives oral daily PrEP a Grade A recommendation for persons at high risk, concluding that there is high certainty that the benefit of oral PrEP is substantial.

 

Some quick summaries on the key studies related to PrEP below:

    •  
  •  

So the PrEP regimen in the above studies and with the most experience was tenofovir fumarate-emtricitabine (TDF/FTC), which is a once daily pill.  Here is an overview of PrEP safety with use of TDF/FTC

  • PrEP  (particularly TDF/FTC use) can be associated with increases in serum creatinine, although serious renal events are rare. Studies have shown that the increase in creatinine is generally reversible with stopping PrEP, and sometimes improves even with PrEP continuation.
  • TDF associated with bone loss, meta-analysis found non-significant increased risk of fracture with PrEP (but heavily weighted by one study).
  • Increased risk of GI adverse events (usually nausea) seen with both TDF monotherapy and TDF/FTC, but risk diminishes over time and serious GI events no different than placebo
  • Development of resistance – in 8 trials of TDF or TDF/FTC only 1.1% had tenofovir resistance, and of the TDF/FTC trials only 8% had emtricitabine resistance.

Those studies have used TDF/FTC, but your patient asks what about TAF/FTC? 

FDA approved TAF/FTC as a second option for PrEP in 10/2019 for adults and adolescents at risk through sexual behaviors, excluding those who have vaginal sex (not studied in this population)

  • Comparing TAF to TDF:
      • TAF is rapidly absorbed by peripheral blood mononuclear cells
        • Higher intracellular activity 
        • Shorter time to effective concentration
        • 90% reduction in plasma tenofovir exposure
            • Improved bone and renal safety.
  • The DISCOVER trial demonstrated TAF/FTC was noninferior to TDF/FTC: Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020;396(10246):239-254. doi:10.1016/S0140-6736(20)31065-5   
      • RCT with 5313 cis-gender MSM and 74 TGW who have sex with men comparing TDF/FTC vs TAF/FTC over 96 weeks, TAF/FTC found to be non-inferior (0.16 infections per 100 person-years with TAF/FTC, 0.34 infections per person years per 100 person-years with TDF/FTC)
          • New diagnoses of HIV were mostly suspected acquired before baseline with false-negative rapid tests or corresponded with low adherence (<2 doses per week) or undetectable tenofovir concentrations on day of HIV diagnosis
      • Adverse events – how did TAF/FTC and TDF/FTC compare? 
        • Overall adverse events low and similar:
            • 7% in each group – most common were bacterial STIs (similar in both groups)
            • GI side effects (nausea and diarrhea) similar between groups
            • Study drug-associated renal adverse events 0.5% TAF/FTC vs 1% TDF/FTC
            • Fractures 53 participants in each group, non-traumatic: 1 TAF/FTC vs 2 TDF/FTC
        • TAF/FTC superior in BMD and renal secondary end-points
            • Hip/Spine BMD stable or increased with TAF/FTC, decreased (~1% decrease at 48w) with TDF/FTC
            • Renal measures better with TAF/FTC (beta-2-microglobulin to creatinine ratio, retinol binding protein to creatinine ratio, quantitative proteinuria, urine protein to creatinine ratio, serum creatinine and creatinine clearance)
                • Quantitative proteinuria 1% (TAF/FTC) to 2% (TDF/FTC)
                • TDF/FTC associated with median decrease in serum Cr of 0.8 µmol/L with median increase in eGFR of 2.3 mL
                • Those on TDF/FTC who switched to TAF/FTC had 3.9 mL/min increase in eGFR at 48 weeks
        • TAF/FTC associated with more metabolic abnormalities
            • Mean weight change at 48w: TDF/FTC -0.1kg vs TAF/FTC +1.1kg 
            • Cholesterol, LDL, HDL all minimal change at week 48 for TAF/FTC, decreased with TDF/FTC

Are there alternative options for PrEP that do not require a daily pill?

On-Demand PrEP

Injectable cabotegravir (CAB) every 8 weeks

Other additional investigational PrEP alternatives that are in the pipeline — it may be a while before we have more results on these agents, but here are some quick introductions

When should PrEP be started?  Many clinics are trying to initiate immediate PrEP, which is likely safe.  The potential loss to follow-up with delaying PrEP was substantial.

  •  There was actually an abstract presented at the Conference for Retroviruses and Opportunistic Infections in 2019, with data from NYC sexual health clinics, where they started patients on immediate PrEP if they had not history of kidney disease or HBV and no acute HIV signs symptoms. If patients had any of those risk factors they waited for lab results. There were only 4 of the patients out of 1387 who had started immediate PrEP who had to be stopped when labs resulted, 2 for positive HIV tests and 2 for GFR <60 ml/L 
  •  

How soon will a patient have protection from HIV?

  • For cis-gender MSM, the International Antiviral Society-USA Panel recommendations from 2020 recommend starting with an initial double dose (2 tablets) of TDF/FTC followed by once daily dosing. This reduces the time to anticipated maximal protection to under 24 hours. Without the initial double dose, the maximal protection is likely achieved approximately 7 days after initiation.

Monitoring while on PrEP: As Meredith mentioned, this may be impacted by clinic capacity and availability of ancillary services

  • The IAS-USA recommends:
    • 1 mo HIV Ag/Ab test
    • Q3 month HIV, gonorrhea/chlamydia, syphilis and pregnancy (if applicable)
    • CrCl at 3 months then annually if low risk, Q3-6 mo if higher risk
    • Annual HCV Ab (more frequent if PWID or MSM who use drugs w sex and have abnormal LFTs).
  •  CDC recommends that patients on PrEP have follow-up visits every 3 months for:
    • HIV test
    • Medication adherence counseling, behavioral risk reduction support, STI symptom assessment
    • Renal function testing at 3 months and every 6 months thereafter
    • Bacterial STI testing every 3-6 months
    • Pregnancy assessment every 3 mo if child-bearing

Remember the PrEP should be considered for other individuals besides MSM who might be in other high risk settings, such as a person who injects drugs.  

If a patient is in monogamous relationship with a person living with HIV who is undetectable, does he need to take PrEP?

Episode Art & Infographics

Goal

Listeners will be able to prescribe pre-exposure prophylaxis, or PrEP, for patients at increased risk for HIV infection.

Learning Objectives

After listening to this episode, listeners will be able to:

  • Identify patients who are appropriate candidates for PrEP
  • Discuss the key trials and evidence supporting use of PrEP for HIV prevention
  • Describe currently recommended regimens for PrEP as well as future agents in the pipeline
  • Compare TDF/FTC and TAF/FTC adverse effect profiles

Disclosures

Our guest (Meredith) is an investigator for research studies funded by Viiv Healthcare and Gilead Sciences, Inc.

Febrile podcast and hosts report no relevant financial disclosures

Citation

Clement, M., Merchant, E., Dong, S. “#14: Fresh stART: PrEP School”. Febrile: A Cultured Podcast. https://player.captivate.fm/10415fa3-4069-4926-8716-979e54a20088

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