HIV PrEP: An Opportunity for Pharmacists

HIV weakens a person’s immune system by specifically attacking the CD4 cells, which are often called T cells. HIV can destroy so many cells over time that the body cannot fight off infections over time, leading to AIDS if left untreated.

The damage to the immune system makes the person more likely to contract opportunistic infections and other infection-related cancers before eventually succumbing to those complications. There is no effective cure that currently exists, but the disease can be controlled with proper medical care.¹

HIV continues to be a serious health issue for parts of the world, including the United States. At the end of 2018, an estimated 1.2 million people aged 13 years and older had HIV in the United States, including an estimated 161,800 (14%) of people whose infections had not been diagnosed. In 2018, 37,968 people received an HIV diagnosis in the United States and dependent areas.²

Access to treatment is essential in reducing transmission. People with HIV who take their medication as prescribed and have an undetectable viral load can stay healthy and have effectively no risk of transmitting HIV to an HIV-negative partner through sex.

HIV-negative people can also decrease their risk for HIV. Pre-exposure prophylaxis (PrEP) is an HIV prevention approach in which people at risk for HIV (current HIV-negative individuals) take daily medicine to prevent it.

PrEP can stop HIV from taking hold and spreading throughout the body and reduce the risk of becoming infected if exposed to the virus. When taken daily, PrEP is highly effective for preventing HIV from sex or injection drug use. It is even more effective when combined with condoms and other prevention tools; however, it is much less effective when not taken consistently.³

The CDC classifies HIV diagnoses into 6 transmission categories: male-to-male sexual contact (MSM), injection drug use, male-to-male sexual contact and injection drug use, heterosexual contact, mother-to-child (perinatal) transmission, and other (includes blood transfusions and unknown causes).² Gay, bisexual, and other men who reported MSM are the population most affected by HIV accounting for 69% of the new HIV diagnoses in 2018. Heterosexuals accounted for 24% of the new diagnoses during that year and people who inject drugs (PWID) accounted for 7%.⁴

PrEP should be considered for people without HIV who are at risk for getting the virus from sex or injection drug use. The federal guidelines recommend that PrEP be considered for HIV-negative individuals who:

Have had anal or vaginal sex in the past 6 months and:

• Have a sexual partner with HIV (especially if the partner has an unknown or detectable viral load).
• Have not consistently used a condom.
• Have been diagnosed with an STD in the past 6 months

PrEP is also recommended for people who injects drugs and

• Have an injection partner with HIV.
• Share needles, syringes, or other equipment to inject drugs (for example, cookers).

PrEP should also be considered for people who have been prescribed non-occupational post-exposure prophylaxis (PEP) and

• Report continued risk behavior.
• Have used multiple courses of PEP.

PrEP can also be an option for couples getting pregnant who have a partner with HIV as it can help protect the mother and baby from getting HIV during conception, pregnancy, or while breastfeeding.³ As long as the risk exists for the individual, adherence to the daily PrEP regimen should be maintained.

Treatment Options

There are 2 agents currently FDA-approved for PrEP, Truvada [Tenofovir disoproxil fumarate 300 mg & Emtricitabine 200 mg (F/TDF)] and Descovy [Tenofovir alafenamide 25 mg & Emtricitabine 200 mg (F/TAF)]. Both were shown to be safe and highly effective in clinical trials.^5,6

PrEP medication

Truvada

Tenofovir disoproxil fumarate 300 mg + Emtricitabine 200 mg (F/TDF)

Descovy

Tenofovir alafenamide 25 mg + Emtricitabine 200 mg (F/TAF)

Dosing

1 tablet PO QD

Unless using a PrEP 2-1-1 schedule

1 tablet PO QD

Alternative dosing (2-1-1 schedule)

Note: while there is substantial published data supporting this strategy, it has not been reviewed by the FDA or recommended by the CDC. The International AIDS Society of the US (IAS-USA), World Health Organization (WHO), and European AIDS Clinical Society (EACS) all endorse the option of this dosing strategy

2-1-1 for MSM with anal exposures only:

2 tablets 2-24 hours before anal sex

(24 hours before for optimal protection)

• Then 1 tablet 24 hours after first dose Then 1 tablet 24 hours after second dose
• If there is another exposure within 7 days of the last dose, take 1 tablet 2-24 hours before anal sex, then 1 tablet 24 hours after first dose then 1 tablet 24 hours after second dose
• If there are continued daily sexual exposures, continue 1 tablet daily until 48 hours has passed since last sexual encounter

For a detailed 2-1-1 guide, click on this link.⁷

Descovy has not been evaluated using a PrEP 2-1-1 schedule

Indications

Approved for use for all adults and adolescents ≥35 kg with indications for PrEP.

Approved for use for adults and adolescents ≥35 kg at risk for sexually acquired HIV, excluding individuals at risk from receptive vaginal/front hole sex and injection drug use only.

Adverse effects

Generally safe and well tolerated

• Nausea or abdominal discomfort (~10%), which usually resolves in a few weeks

• Small decrease in eGFR, which improves upon discontinuation of Truvada
• Slightly decreased bone density, but no increased risk of fractures

• Small increase in LDL cholesterol
• Slight increase in body weight

Other notes

Estimated GFR or CrCl by serum labs should be ≥60 mL/min (Cockcroft-Gault) to safely use Truvada

• A generic form of Tenofovir disoproxil fumarate + Emtricitabine (F/TDF) is anticipated in October 2020.

Estimated GFRF or CrCl by serum labs should be ≥30 mL/min (Cockcroft-Gault) to safely use Descovy

Time to Protection

Time to maximum protection varies by site of exposure:

• Rectal tissue: about 7 daily doses
• Cervico-vaginal tissue: about 21 daily doses, but should not be a reason to not Rx PrEP
• PWID: about 21 daily doses for blood exposures

PrEP Initiation

If there are no contraindications and the patient wants to use PrEP, it can be initiated.

Same-day PrEP prescriptions are encouraged when possible. A prescription should be written and PrEP started on the same day a patient comes in for consultation when:

• the patient has a negative HIV test within the last 2 weeks and no HIV exposures since this test
• all laboratory testing is obtained that day
• the patient has no symptoms of acute HIV infection

If it has been more than 2 weeks since baseline labs were obtained, repeat an HIV test and start PrEP the same-day while awaiting results of the repeat HIV test.

• To transition from PEP to PrEP, check an HIV fourth generation Ag/Ab test while on week 4 of PEP and prescribe PrEP.

Monitoring

Baseline:⁸

Tests

Comments and rationale

HIV antigen/antibody or antibody-only test:

Rapid HIV Ab test, or fourth generation (Quest #91431) or HIV RNA PCR (Quest #40085)

Consider testing for acute HIV infections in all patients who are initiating PrEP with either an individual HIV RNA, a pooled HIV RNA or a fourth generation combined HIV Ag/Ab assay, especially if they have had a high-risk exposure in the prior month. Test for acute HIV infection in all patients with symptoms concerning for acute HIV infection.

If the patient has acute or chronic HIV infection, they must receive 3 active HIV medications for treatment and risk resistance if taking only PrEP.

Renal function

CrCl should be ≥60 mL/min (Cockcroft-Gault) to safely use Truvada or ≥30 mL/min to safely use Descovy.

Hepatitis B (HBV) serologic screening (surface antigen)

Truvada is active against HBV. Patients with chronic HBV can use Truvada for PrEP, but should have liver function tests monitored regularly during PrEP use and after discontinuing PrEP, and should be cautioned that hepatitis can flare if Truvada is discontinued. Patients who are HBsAg negative should be offered HBV vaccination if not previously infected or immunized.

Hepatitis C (HCV) antibody

Determine baseline HCV infection status and obtain repeat testing at least yearly among MSM, PWID, and others with ongoing risks of exposure.

STIs (based on patient sexual practices)

Test patients on PrEP for syphilis and for urethral, rectal, and pharyngeal gonorrhea (GC) and chlamydia (CT) based on reported exposure routes (not based on gender/sexuality) every 3 months. Consider using self-collected swabs for GC/CT testing. Consider offering the human papillomavirus (HPV) and hepatitis A virus (HAV) vaccines if not previously vaccinated.

Pregnancy test (when appropriate)

People who can become pregnant (reproductive-age cisgender women, some transgender men and non-binary people) should receive a pregnancy test and have contraception plans reviewed. In patients trying to conceive, PrEP should be coordinated with prenatal care with attention to the partner’s reproductive and breastfeeding plans. Descovy is not approved for use as PrEP in this population. Perinatal HIV/AIDS consultation is available 24/7 at 888-448-8765.

Ongoing monitoring and support for patients using PrEP

Monitoring recommendations are currently identical for Truvada and Descovy as well as for people using 2-1-1 dosing.

Timeframe

Action

30 days after initiation

In-person follow-up visit highly recommended for patients 24 years old and under or those who may have difficulties with adherence.

A phone call is a reasonable alternative for other patients.

Assess for:

• Adverse effects and patient interest in continuing.
• Adherence: link to regular habits, set reminders, reinforce importance of dosing schedule, and address any challenges the patient has faced.
• Ongoing risk and provide risk reduction counseling.
• Signs and symptoms of acute HIV infection.

Prescribe additional 60-day supply with no refills

Every 3 months

Labs

Visit

Refills

• At visit: adherence and risk reduction counseling.
• HIV test: fourth generation antigen/antibody test preferred.
• Serum creatinine: stop if eGFR declines.
• STI screening for syphilis and for urethral, rectal, and pharyngeal GC and CT based on reported exposure routes (not based on gender/sexuality). Consider using self-collected swabs for GC/CT testing.
• Pregnancy test for appropriate patients.
• Prescribe 90-day supply if HIV test negative at each visit.

Every 12 months or more often based on assessed risk

• HCV antibody, particularly for MSM and PWID.

Positive HIV test while on PrEP

• Discontinue PrEP to avoid development of HIV resistance.
• Start patient on HIV antiretroviral treatment as soon as possible in accordance with HIV treatment guidelines⁹ and/or refer to an HIV provider as soon as possible.
• For questions and support, call the National HIV Clinicians Consultations Center: 800-933-4313.
• Order HIV genotype and document results.
• Report the test result to your local health department.

California Senate Bill 159 (CA SB 159)¹⁰

Bill 159, approved in California in October 2019, eliminates mandatory doctor visits and bars insurance companies from requiring prior authorization for the drugs necessary for PrEP and PEP. The bill, as it relates to PrEP and pharmacy, would authorize a pharmacist to furnish PrEP and PEP in specified amounts and would require a pharmacist to furnish those drugs if certain conditions are met, including that the pharmacist determines the patient meets the clinical criteria for PrEP or PEP consistent with federal guidelines.

It would require a pharmacist to complete a training program approved by the board before furnishing PrEP or PEP. The bill will be implemented in July.

A key difference from the allowances of this bill and standard PrEP provider care is that the trained pharmacist is only allowed to dispense at least a 30-day supply up to a 60-day supply (if the screening conditions are met) so as to direct the patient to their PrEP prescriber for additional monitoring and prescription refills.

The pharmacist may not furnish a 60-day supply of PrEP to a single patient more than once every 2 years, unless directed otherwise by a prescriber. The bill also requires the pharmacists be trained on the different coverage options for PrEP.

PrEP Coverage Options

Insured patients

Many private insurers cover PrEP but may require prior authorization (PA). PAs for Truvada will no longer be allowable after July 2020. Approval for coverage typically requires documentation of all of the following:

Patient has:

• been determined to be at high risk for HIV infection
• received counseling on safer sex practices and HIV risk reduction
• no clinical symptoms consistent with acute viral infection
• no recent (<1 month) suspected HIV exposures
• a confirmed negative HIV status within the past week

Adolescents covered on their parents’ plan can keep their information confidential by signing up at myhealthinfo.org. Medi-Cal (California Medicaid) does not require a PA for PrEP. Have the pharmacy bill to the State Medi-Cal HIV carve-out instead of the managed care plan to help ensure Medi-Cal coverage.

• For adolescents, the Medi-Cal Minor Consent Program can help pay for PrEP/PEP and keep the services confidential.
• ICD-10 codes for PrEP include: Z20.6: Contact with and (suspected) exposure to HIV. Z20.2: Contact with and (suspected) exposure to infections with a predominantly sexual mode of transmission. Z71.7: HIV counseling Other codes are on page 42 of the CDC Clinician Supplement⁵
• If patient needs help with co-pays, Gilead (maker of Truvada and Descovy) has a co-pay assistance program for up to $7200 annually for either agent. Visit gileadadvancingaccess.com or call 877-505-6986.
• Other payment assistance programs are listed on the Fair Pricing Coalition website.¹¹

Uninsured patients

The Gilead Advancing Access PrEP medication assistance program will provide monthly Truvada or Descovy deliveries to the patient or clinic at no cost for those without prescription coverage and who meet income guidelines (500% FPL).

• Call 800-226-205 for inquiries or to apply by phone, Monday-Friday, 6 am-5 pm PST.
• Fax the completed application and proof of income to 855-330-5478 or services.gileadhiv.com/content/pdf/gilead_enrollment_form.pdf.
• If approved, 1 bottle (30-day supply) will be available for pickup at any non-Kaiser pharmacy. For pickup, provide an ID, bin, group, or PCN number (provided by Gilead). Refills can be coordinated with the pharmacy.
• Alternatively, medication bottles may also be shipped to a clinic in 3 to 14 days. A Gilead representative will call the provider before the second bottle is sent to confirm refill if continuing to ship to clinic.
• Patients must re-apply (ie resubmit proof of eligibility) every 12 months.
• US and undocumented residents are eligible. SSN is not required. Proofs of income include W2, 1040 tax return, 2 pay stubs from the last 90 days or letter stating monthly income. Letter may also state residence address. Letter must be signed and dated, but does not need to be notarized.

The Ending the HIV Epidemic: Ready, Set, PrEP program (getyourprep.com) provides monthly Truvada or Descovy deliveries to the patient or clinic at no cost for those without prescription coverage, regardless of income, for up to 200,000 patients per year. Patients must provide proof of lack of prescription coverage, a recent negative HIV test result, and a current prescription for PrEP. State programs for PrEP are also available to assist with cost and access.

Telehealth and Further Direction

Numerous barriers prevent access to PrEP. Individual awareness of HIV risk and willingness to take PrEP, geographic distance to care, provider awareness of PrEP, and willingness to prescribe, cost or insurance access, and adherence all present as obstacles along the PrEP continuum of care.

Stigma also prevents HIV preventative care for many. For example, fewer than 50% of MSM disclose their sexual orientation to their primary care provider (PCP) due to discomfort in healthcare settings and fear of judgement. Novel technology-based strategies can be employed as attempts to circumvent these barriers and scale-up PrEP coverage for at-risk populations.¹²

Provider-to-patient telehealth modalities provide a function of remote PrEP prescribing and are designed to overcome geographic barriers, connect at-risk persons directly to PrEP-trained providers, and may reduce barriers, such as fear of discrimination.

Many of the following programs allow patients to use self-testing/self-collection kits for HIV and other STIs to send in for screening. Examples include:

• PrEPTECH, a pilot program in California that uses a mobile-friendly website, with PrEP intake appointments by phone, opt-in text message adherence reminders, and PrEP medication by mail. The program recruits participants via ads on Grindr, a popular dating app.
• Gay City, an LGBTQ community center in Seattle, in which HIV counselors provide on-site care and PrEP is prescribed using videoconference visits with a remote PrEP specialist.
• PrEPIOWA, an intervention in which clinical pharmacists prescribe medications and counsel patients via telemedicine, with physician support available as needed.
• Plushcare.com, a mobile/web platform that offers videoconference visits for PrEP prescribing in many states.
• Nurx.com, a mobile/web platform that offers PrEP after a text message-based intake by a physician.

Provider-to-provider telehealth modalities function as distance mentorship and clinical consultation for community PrEP prescribers via videoconference with infectious disease specialists plus a multidisciplinary support team and are designed to build capacity of primary care providers to prescribe PrEP.

An example of this type of modality is the Mountain West AIDS Education and Training Center Extension for Community Healthcare Outcomes program, which offers quarterly PrEP didactics and case-based discussion via videoconference, connecting community PrEP providers in 6 states with University of Washington specialists, including ID providers as well as pharmacy, psychiatry, and social work experts.

Store-and-forward consults (e-Consults) serve as electronic healthcare record (EHR)-based specialist consultation without a face-to-face visit and are designed to reduce barriers to access to PrEP specialists, support prescribing, and build capacity of non-specialists to prescribe PrEP.

The Veteran’s Health Administration has a well-established e-Consult system to support PCPs in PrEP prescribing and the University of Washington recently introduced infectious disease e-Consults, including an option for PrEP prescribing guidance.

The outcomes data for all of these modalities are currently limited but show promise. Technology-based interventions can address gaps in the PrEP care continuum.

As the programs continue to evolve, opportunities can present themselves for pharmacists to take an active role in PrEP care. Novel funding sources for the programs—as well as advocacy to change laws and regulations to better support and reimburse such models and support collaborative practice pharmacist prescribing&mdash;must occur so they can be implemented in regions with the greatest need for PrEP.

About the AuthorsJennifer Nguyen is a PharmD candidate at Marshall B. Ketchum University’s College of Pharmacy, anticipated to graduate in spring 2021.

Jonathan Ogurchak, PharmD, CSP, is the co-founder and CEO of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.

References

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• HIV PrEP Quick Guide PAETC-CDPH 2012. Pleaseprepme.org. https://www.pleaseprepme.org/sites/default/files/file-attachments/CA%20HIV%20PrEP%20quick%20guide%20-PAETC-CDPH-%2012.12.2019%20ADA%20final.pdf. Published 2020. Accessed June 20, 2020.
• PrEP 211 Study Info Flyer — English. Sfaf.org. https://www.sfaf.org/wp-content/uploads/downloads/PrEP-211-study-info-flyer-ENGLISH-FINAL.pdf. Published 2020. Accessed June 20, 2020.
• Pre-Exposure Prophylaxis (PrEP): A primer for primary care providers. Sfcityclinic.org. https://www.sfcityclinic.org/sites/default/files/services/PrEP%20primer_May%202014.pdf. Published 2020. Accessed June 20, 2020.
• What's New in the Guidelines? Adult and Adolescent ARV. AIDSinfo. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0. Published 2020. Accessed June 20, 2020.
• Bill Text - SB-159 HIV: Preexposure and Postexposure Prophylaxis. Leginfo.legislature.ca.gov. https://leginfo.legislature.ca.gov/faces/billNavClient.xhtml?bill_id=201920200SB625. Published 2020. Accessed June 20, 2020.
• Pharmaceutical Company Patient Assistance Programs and Co-Payment Assistance Programs for Pre-exposure Prophylaxis (PrEP) and Post-exposure Prophylaxis (PEP). NASTAD. https://www.nastad.org/resource/pharmaceutical-company-patient-assistance-programs-and-co-payment-assistance-programs-pre. Published 2020. Accessed June 20, 2020.
• Touger R, Wood BR. A Review of Telehealth Innovations for HIV Pre-Exposure Prophylaxis (PrEP). Curr HIV/AIDS Rep. 2019;16(1):113-119. doi:10.1007/s11904-019-00430-z