Table of Contents

• How to Take a Sexual History to Evaluate Risk for HIV

• PrEP Frequently Asked Questions

  1.  What is PrEP?
  2.  Who can prescribe PrEP?
  3.  Who can I consult if I have questions about PrEP?
  4.  Which patients should be offered PrEP? 
  5.  What if my patient reports recent high-risk exposure?
  6.  Who is not eligible for PrEP?
  7.  Can adolescents take PrEP?
  8.  How quickly does PrEP provide protection?
  9.  Is PrEP safe?
  10.  What baseline assessment and monitoring is required for individuals on PrEP?
  11.  How do I assess for adherence?
  12.  What HIV tests are recommended for HIV screening?
  13.  If acute HIV is possible, can I still start PrEP?
  14.  What patient education is recommended for patients considering PrEP or taking PrEP?
  15.  How is PrEP prescribed?
  16.  What are the insurance and payment options for PrEP?
  17.  Is PrEP recommended if the partner is virologically suppressed?
  18.  Does a person living with HIV need treatment if their partner is on PrEP?
  19.  Can PrEP be used to help sero-different couples conceive?

• Resources

• Supplemental Information:

  • The evidence base for PrEP

  • Studies among women only

• References

How to Take a Sexual History to Evaluate Risk for HIV

Taking a comprehensive sexual history ensures that the provider will be able to identify patients at high risk of HIV acquisition as well as other STDs and unintended pregnancy. A sexual history should normalize sex (i.e. “sex is a natural part of life”), assure environment and confidentiality, be non-judgmental, and avoid assumptions. The acronym P.R.E.P. (Partners, Receptive or Insertive, Ever had an STD, Protection/PrEP/Pregnancy) can be used when taking a comprehensive sexual history (see below).

PrEP Frequently Asked Questions

1. What is PrEP?

PrEP stands for HIV pre-exposure prophylaxis. It is the use of antiretroviral medication to prevent acquisition of HIV infection. PrEP is used by HIV uninfected people who are at risk of being exposed to HIV through sexual contact or injection drug use. At present, the only medication that is FDA-approved for PrEP is oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC), which is available as a fixed combination once daily tablet called Truvada^*. It is also commonly used in the treatment of HIV in conjunction with other medication.

For the rest of this article, the term PrEP refers to single daily dose TDF-FTC unless otherwise stated.

*Recently Descovy, a fixed-dose combination similar to Truvada, was approved for HIV treatment; this pill includes a novel, tenofovir pro-drug (tenofovir alafenamide) in addition to emtricitabine.  However, data are not yet available to support the use of Descovy as PrEP. 

2. Who can prescribe PrEP?

Any licensed prescriber can prescribe PrEP. Specialization in infectious diseases or HIV medicine is NOT required. Primary care providers should consider offering PrEP to all eligible patients at risk of HIV on a routine basis.

3. Who can I consult if I have questions about PrEP?

If PrEP questions arise, clinicians can consult the University of California, San Francisco Clinician Consultation Center. The center can also answer questions pertaining to HIV post-exposure prophylaxis (PEP).

4. Which patients should be offered PrEP?

PrEP should be offered to the patient populations below.

The use of PrEP if the positive partner is virologically suppressed is discussed in Q17. For information on the use of PrEP to reduce HIV transmission in couples attempting to conceive see Q19.

5. What if my patient reports recent high-risk exposure?

Evaluate patients for acute HIV if they report high-risk exposure within the last month. Symptoms of acute HIV are fever, swollen lymph nodes, sore throat, myalgia, and arthralgia, and risk factors include unprotected sex or sharing needles. In addition, if the exposure was in the past 72 hours, offer Post-Exposure HIV prophylaxis (PEP). If PEP is not indicated and the risk of HIV acquisition is ongoing, offer PrEP.

6. Who is not eligible for PrEP?

• People with HIV. Individuals must be confirmed as HIV-negative before initiating PrEP. Excluding those with acute HIV infection is critically important, as there is a risk of developing resistant HIV if they inadvertently start on TDF-FTC as PrEP. TDF-FTC is only effective as a treatment for HIV infection when it is combined with an agent from another class of antiretrovirals.
• People with renal insufficiency. Providers should confirm that the patient’s calculated creatinine clearance is >60 mL/minute (Cockcroft-Gault formula) before initiating PrEP.
• People who are not ready to adhere to therapy. Those who indicate that they are not ready to adhere to daily oral therapy should not be prescribed PrEP since efficacy is extremely limited when patients do not take the medication daily.

7. Can adolescents take PrEP?

Yes. Based on the experience of using TDF-FTC for HIV treatment and post-exposure prophylaxis among adolescents, the CDC and the International Antiviral Society-USA now recommend PrEP for adolescents at high risk for HIV infection. Studies are still underway, however, and pilot data suggest that young people may have special issues maintaining sufficiently high adherence for HIV prevention.^5,6

As with every patient, but especially with younger adolescents:

• Carefully weigh the potential benefits and risks, including acquiring HIV infection.
• Make clear that the efficacy of PrEP is highly dependent on strict adherence.
• Refer to the institution’s policy or consult with the institution’s legal department about consent to care for adolescents under 18 years of age according to California state law.

8. How quickly does PrEP provide protection?
 

Data from pharmacokinetic studies suggest that individuals need to take PrEP for:

• At least 7 days to achieve protective levels in rectal tissue and plasma.^4,7
• At least 20 days to achieve protective levels in cervicovaginal tissue.

9. Is PrEP safe?

TDF-FTC as PrEP is considered safe and is well-tolerated. Although TDF-FTC has caused renal toxicity and decreased bone mineral density when used for HIV treatment and administered for months and years, in PrEP studies which began in 2007, TDF-FTC has not caused serious safety concerns.^8,9,10 Mild decrease in renal function has been observed in patients on PrEP. Renal function should be assessed at baseline, 3 months following initiation of PrEP, and then every 6 months. TDF-FTC as PrEP is contraindicated for patients with creatinine clearance < 60 mg/dl. Mild decrease in bone mineral density has also been observed in patients on PrEP. Notably, no pathologic fractures have been documented. Performing a DEXA scan at initiation of PrEP is not currently recommended.

Since TDF-FTC is actively eliminated by the kidneys, it should be administered with care in patients taking medications that are eliminated by active tubular secretion (e.g., acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, and high-dose or multiple non-steroidal anti-inflammatory drugs). Drugs that decrease renal function may also increase concentrations of TDF-FTC.

Pregnancy: PrEP is considered safe for women of child-bearing age. TDF-FTC is Pregnancy Category B.  Available data suggest that TDF-FTC does not increase risk of birth defects, although there are not enough data to exclude the possibility of harm. PrEP is often used in pregnancy if the risk of ongoing HIV transmission is sufficiently high (such as in a sero-different partnership) and because pregnancy itself is associated with an increased risk of HIV acquisition.

10. What baseline assessment and monitoring is required for individuals on PrEP?

11. How do I assess for adherence?

Strict adherence to PrEP is critical for maximum efficacy. The likelihood of adhering should be assessed at the initial visit with questions such as, “Can you commit to take a pill every day?”.  Adherence at follow-up visits should also be evaluated, for example by asking, “Over the past four days, how many doses of PrEP have you taken?”.

12. What HIV tests are recommended for HIV screening?

As described in Q6., excluding HIV infection prior to starting PrEP is critically important. TDF-FTC as PrEP does not constitute a full HIV treatment regimen, so patients with HIV who are on PrEP are at risk of developing a resistant strain. HIV testing should be conducted immediately prior to starting PrEP, ideally the same day the prescription is provided. DHSP recommends using a lab-based fourth-generation (preferred) or viral load due to increased sensitivity for acute HIV, however, CDC states that any HIV test (except an oral rapid test) can be used for the baseline HIV testing. For a list of FDA-approved third- and fourth-generation tests, visit https://stacks.cdc.gov/view/cdc/23447.

If the patient has symptoms of acute HIV infection or risk factors for acute HIV infection a nucleic acid amplification test (NAAT, viral load) should be performed. PrEP should not be started unless the result is negative. Symptoms of acute HIV are fever, swollen lymph nodes, sore throat, myalgia, and arthralgia, and risk factors include unprotected sex or sharing needles.

For more information on HIV, including detection of acute HIV, visit the CDC STD Treatment Guidelines, section HIV Infection: Detection, Counseling, and Referral.

13. If acute HIV is possible, can I still start PrEP?

No. PrEP initiation should be deferred until HIV infection is ruled out.

CDC Guidelines suggest the following options for patients with signs and/or symptoms of acute HIV infection within the prior four weeks (see algorithm on p. 33 of the CDC PrEP Guidelines).³

• Option 1 - Retest in one month; defer decision to start PrEP.
• Option 2 - Send blood for HIV antibody/antigen assay (i.e., fourth generation HIV testing). If the patient is negative, it is acceptable to initiate PrEP.
• Option 3 - Send blood for HIV-1 viral load (VL) assay.
  • If the patient has VL<50,000 copies/mL, PrEP should be deferred while testing is repeated
  • If the VL is undetectable and the patient has no signs/symptoms the day of the blood draw, it is acceptable to initiate PrEP.
  • If the VL is undetectable and the patient has signs/symptoms the day of the blood draw, retest in one month and defer decision on PrEP.
  • If the patient has VL>50,000, they are HIV-infected and are not eligible for PrEP.   

14. What patient education is recommended for patients considering PrEP or taking PrEP?

Prior to prescribing PrEP, patients should be given information about the medication, the signs and symptoms of acute HIV, and the importance of adherence. In addition, PrEP should be prescribed as part of a comprehensive HIV/STD prevention plan. Patient centered risk-reduction counseling regarding prevention of STDs and HIV, the use of condoms and, where applicable, safe injection practices, is recommended.

Patients can be encouraged to visit the Get PrEP LA website (www.getprepla.com) to learn more about PrEP, including what PrEP is, how it works, who it is right for, and if it is safe.

Excerpt from www.getprepla.com

15. How is PrEP prescribed?

If PrEP questions arise, clinicians can consult the University of California, San Francisco Clinician Consultation Center. The center can also answer questions pertaining to post-exposure prophylaxis (PEP).

16. What are the insurance and payment options for PrEP?

Health Insurance

Many insurance plans cover PrEP. TDF-FTC is on the California Medi-Cal formulary and   Medi-Cal completely covers the cost of TDF-FTC as PrEP, as well as medical visits and laboratory testing. Prior authorization is NOT required.

Several programs have been established to help cover the cost of PrEP and associated care, including the following three.

Gilead Advancing Access Patient Assistance and Co-pay Coupon Programs

The manufacturer of Truvada (Gilead) has established programs to help cover the cost of PrEP. Advancing Access provides assistance to patients who are uninsured or underinsured, or who need financial assistance to pay for Gilead medications.

• Access to counselors who can help patients and their providers with insurance-related questions, including coverage options.
• Patient Assistance that provides medications at no charge for eligible patients with no other insurance options. Patients must have annual income less than 500% of the Federal Poverty Level (FPL). In 2017, 500% of FPL is $60,300 for a one-person household.
• Co-pay assistance for eligible patients (up to $3,600 in co-pays per year with no monthly limit).

For more information, call 1-800-226-2056 or visit www.gileadadvancingaccess.com

Los Angeles County Department of Public Health PrEP Centers of Excellence (PCOE)    

In August 2016, DHSP funded nine community agencies and clinics at 14 sites throughout Los Angeles County to serve as “PrEP Centers of Excellence”. The PCOEs offer PrEP at low cost for patients at high risk for HIV acquisition who are uninsured or underinsured.  These PCOEs are community clinics with expertise in sexual health, which also offer essential services to address social determinants of health that prevent patients from achieving optimum health, such as benefits navigation, mental health, and substance abuse referrals. 

• Patients must be LA County residents
• Patients must have an income of <500% FPL

For more information, visit http://getprepla.com/centers-excellence.html or call 1-844-YEA-PREP.

Patient Access Network (PAN) Foundation:

The PAN Foundation offers services to people with chronic disease for whom cost limits access to critical medical treatment due to rising deductibles and co-pays.

• Offers one-time grants to cover up to $7,500 of prescription costs for one year.
• Patient must have private insurance, Medicare, or Medicaid.
• Patient must have an income <500% FPL or if their income is above this they may still qualify if their prescription costs exceed 10% of their income.

For more information, call 1-866-316-7263 or visit www.panapply.org

The retail cost of PrEP medication is approximately $1,400 to $1,600 per month.

17. Is PrEP recommended if the partner is virologically suppressed?

Whether the HIV-negative partner should take PrEP if the positive partner has an undetectable HIV viral load is a matter of substantial debate. This decision must be individualized and may depend on the HIV-positive partner’s virologic control, condom use and other partners that the HIV-negative partner may have. Recent findings from a large cohort study among stable, sero-different couples where the HIV-positive partner was virologically suppressed suggested that in this situation the risk of seroconversion may be negligible.¹¹ Reasons why PrEP might still be offered include lapses in adherence to antiretroviral therapy and differences between plasma and seminal/vaginal fluid viral load measurements.¹² Additionally, research suggests that much of HIV transmission is from non-main partners.¹³

18. Does a person living with HIV need treatment if their partner is on PrEP?

Yes. The Los Angeles County Public Health Department and national experts recommend that all people with HIV be treated, regardless of clinical status or CD4 cell count.^14,15 Virologic suppression of the HIV-infected partner protects his or her health and the health of the HIV uninfected partner.¹⁶

19. Can PrEP be used to help sero-different couples conceive?

PrEP may be one of several options to help protect the HIV-negative partner of an HIV positive person during attempts to conceive. Expert consultation is recommended in order to tailor the approach to the specific needs of each couple. It is recommended that in all cases, the HIV-infected partner is given antiretroviral therapy (ART), and that conception is not attempted until virologic suppression is achieved. Extensive counseling of both partners is recommended regardless of the specific approach selected. For more information, consult federal guidelines.¹⁷

Supplemental Information

The Evidence Base for PrEP

Clinical trials of PrEP using intention to treat analysis show risk reductions of 44-75% (see table below) but in all PrEP clinical trials to date, efficacy appeared to depend on adherence.^18,19 According to a dedicated analysis of adherence of those trials, PrEP was non-efficacious when adherence was low, but when moderate or high adherence was achieved, efficacy was modest or relatively high, respectively.¹⁹ Among the subjects with detectable plasma tenofovir levels in four studies, efficacy ranged from 74 to 92%^20,21,22,23 Modeling studies have shown that PrEP decreases the risk of HIV up to 99% when taken as prescribed.¹

Adherence to PrEP was also found to be highly associated with reduction of HIV risk in an open-label study (iPrEX OLE).²⁴ Among participants with drug detected by dried blood spot, HIV incidence ranged from 4.7 infections per 100 person-years (no drug detected) to 0.6 per 100 person-years (two to three tablets per week). There were no HIV infections in participants using four or more tablets per week. Another study suggested that an “on demand” regimen (i.e., use of PrEP just before and after sex) might also reduce HIV acquisition among MSM (IPERGAY²⁵), although the frequency of sexual acts among men in that study was high enough that they closely approximated four tablets weekly (which, as mentioned above, provides very high levels of protection). The effectiveness of “on demand” PrEP among those using PrEP less frequently is unknown. At this time, the only recommended PrEP dosing strategy is daily.³ In summary, adherence is critical.

Summary of Trials Using Daily Oral PrEP

Studies Among Women Only

Two trials of PrEP in women were stopped early for futility by their respective data safety and monitoring boards.^26,27 A determination of futility is made when it appears that no evidence of efficacy would be found in the future based on the results collected up to that point. Low adherence among the participants was thought to be a substantial factor in the futility finding. Other studies that included both men and women (TDF2, Partners PrEP) in which higher levels of adherence were achieved did show efficacy among women. Recent data suggest that women may need higher levels of adherence than men, in order to achieve protective levels of drug in the female genital tract. Current clinical guidelines include women as appropriate candidates for PrEP.

References

1. Supervie V, Barrett M, Kahn JS, et al. Modeling dynamic interactions between pre-exposure prophylaxis interventions & treatment programs: predicting HIV transmission & resistance. Sci Rep. 2011;1:185. doi:10.1038/srep00185.
2. Los Angeles County. PrEP Guidelines: Who Needs PrEP in Los Angeles County.  http://ph.lacounty.gov/dhsp/docs/PrEPguidelines9-2016.pdf. Updated September 30, 2016. Accessed September 14, 2017.
3. Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update: a clinical practice guideline. https://stacks.cdc.gov/view/cdc/48352. Published September 2017.
4. Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update: clinical providers’ supplement. https://www.cdc.gov/hiv/pdf/guidelines/cdc-hiv-PrEPProviderSupplement-2017.pdf Published September 2017
5. Hosek S, Siberry G, Bell M, et al. Project PrEPare (ATN082): The Acceptability and Feasibility of an HIV Pre-Exposure Prophylaxis (PrEP) Trial with Young Men Who Have Sex with Men. J Acquir Immune Defic Syndr. 2013;62(4):10.
6. Hosek, S, et al. ATN 110: An HIV PrEP Demonstration Project and Safety Study for Young Me (18·22) who Have (high-risk) Sex with Men in the United States. lAS 2015 Vancouver July 19-23.
7. Seifert S, Glidden D, Anderson P, et al. Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex with Men. Clin Infect Dis. [serial online]. 2015;60(5):804-810.
8. Krakower D, Mayer KH. What primary care providers need to know about preexposure prophylaxis for HIV prevention: a narrative review. Ann Intern Med. 2012;157(7):490-7.
9. Grohskopl LA, Chlllag KL, Gvetedze R, et al. Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2013;64(1):79-86.
10. Liu AY, Vittinghoff E, Sellmeyer DE, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011;6(8): e23688.
11. Rodger A, Bruun T, Camblano Vet al. HIV Transmission Risk Through Condomless Sex If HIV+ Partner On Suppressive ART: PARTNER Study. CROI. Boston, MA, 2014.
12. Gianelia S, Smith DM, Vargas MV, et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1-infected men who have sex with men. Clin Infect Dis. 2013;57(3):441-7.
13. Panel on treatment of HIV·infected pregnant women and prevention of perinatal transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf. Updated October 26, 2016. Accessed September 21, 2017.
14. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents: Department of Health and Human Services, 2013.
15. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection:2012 recommendations of the International Antiviral Society-USA panel. JAMA. 2012;308(4):387-402.
16. Cohen MS, Chen YO, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493·505.
17. Kawwass JF, Smith DK, Kissin DM, et al. Strategies for Preventing HIV Infection Among HIV-Uninfected Women Attempting Conception with HIV-Infected Men — United States. MMWR Morb Mortal Wkly Rep 2017;66:554–557. DOI: http://dx.doi.org/10.15585/mmwr.mm6621a2. 
18. Van der Straten A, Van Damme L, Haberer JE, Bangsberg DR. Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention. AIDS. 2012;24;26(7): F13-9.
19. Koanlg W, Lyles C, Smith DK. Adherence to Antiretroviral Medications for HIV Pre- Exposure Prophylaxis: Lessons Learned from Trials and Treatment Studies. Am J Prev Med. 2013;44(1 Suppl 2): S91-8.
20. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587-99.
21. Baeten JM, Donnell D, Ndase P. Et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399-410.
22. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367(5):423-34.
23. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV Infection in injecting drug users In Bangkok. Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo controlled phase 3 trial. Lancet. 2013;381(9883):2083·90.
24. Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Dis. 2014;14(9): 820-829.
25. Molina J-M, Gapitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015;373(23):2237-2246.
26. Van Damme L, Cornell A, Ahmed K, et al. Preexposure prophylaxis for HIV Infection among African women. N Engl J Med. 2012;367(5):411·22.
27. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women. N Engl J Med. 2015;372(6):509-518.