HIV pre-exposure prophylaxis (PrEP) for individuals at risk for HIV infection

Mark W. Hull MD MHSc (biography and disclosures)
Disclosure: Member of the advisory board with Gilead, Viiv and Merck. Member of the speakers’ bureau with Gilead and Merck. Mitigating potential bias:

1. Recommendations are consistent with current practice patterns
2. Treatments or recommendations in this article are unrelated to products/services/treatments involved in disclosure statements

What I have noticed

I provide HIV care in the St. Paul’s Hospital HIV Specialty Clinic. Although overall rates of new diagnoses of HIV in British Columbia have declined with expanded uptake of antiretroviral therapy, over the last five years, on an ongoing basis, we have seen new HIV infections occurring in young gay, bisexual and other men who have sex with men (MSM).  The majority of these individuals had had a prior negative HIV test within the last year, or were presenting with signs or symptoms supportive of an acute HIV infection, suggesting recent exposure and transmission of HIV infection, highlighting the need for novel HIV prevention strategies.  In fact, current data in Vancouver suggests that in 2017 over 70% of all new diagnoses occurred in MSM, and that 60% of these infections were acute/recent infections¹. These individuals often were very traumatised by their diagnosis and a commitment to life-long antiretroviral therapies. One of the promising biomedical prevention strategies now available is the use of HIV Pre-Exposure Prophylaxis (PrEP), where HIV negative individuals take a combination antiretroviral medication – tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) to prevent HIV infection in the event of a high-risk exposure (sexual or needle sharing).

What changed my practice

In 2010 the first clinical trial of PrEP was published, and found that compared to placebo, use of TDF/FTC by individuals at high risk for HIV infection reduced HIV incidence by 44%, and in post-hoc analysis, by over 90% in adherent individuals².  Additional clinical trials and observational studies have shown similar high rates of efficacy for HIV prevention^3-5. The US Centers for Disease Control published guidelines for clinicians in 2014 ⁶ and Canadian guidelines have been released in late 2017 ⁷. In British Columbia, publically funded PrEP, provided through the BC Centre for Excellence in HIV/AIDS (BC CfE), was made available in early 2018 for at-risk individuals. In order for PrEP to be successful in BC, wide spread access to willing primary care prescribers is required.

What I do now

How do I assess and counsel someone for PrEP?

1. HIV PrEP should be considered in all MSM with markers of increased HIV risk, and for all sexual and injecting partners of HIV-positive individuals who have not achieved full virologic suppression on antiretrovirals. BC HIV PrEP Baseline Assessment tool: http://www.cfenet.ubc.ca/sites/default/files/uploads/publications/centredocs/prep_baseline_assessment_form_v2018_03_13.pdf.
2. MSM can be evaluated for increased HIV risk using simple clinical markers which have been shown to be associated with significant increased risk for HIV:
   1. Evidence of sexually transmitted infections such as infectious syphilis and rectal gonorrhea or chlamydia, particularly if infection occurred within the preceding two years.
   2. Use of a clinical risk index known as the HIRI-MSM index⁸ which evaluates risk by age of the individual, number of male partners, having had condomless receptive anal sex, insertive anal sex with HIV positive individuals, and use of crystal methamphetamine all within the prior six months. Individuals who score >10 on this risk index would be considered to be at higher risk for HIV and would qualify for PrEP. It should be remembered that risk behaviour may change, and the HIRI risk index can be repeated over time.
   3. We have created a standard checklist to help prescribers complete a PrEP risk assessment and document other pertinent information such as syndemic substance use or mental health concerns. This and other documents such as the PrEP Prescription Form and PrEP laboratory documents are available at: http://www.cfenet.ubc.ca/hiv-pre-exposure-prophylaxis-prep/documents
3. PrEP, if used on a daily basis, reduces risk for HIV infection from an exposure by over 97%.
4. PrEP is not immediately effective and takes one week to reach protective levels (during that week other protective strategies are still required), and if over 3 doses a week are missed then protection is significantly reduced.
5. Common side effects include nausea, gas, bloating, stomach upset and headache, and very rare risk of renal impairment. Common side effects usually settle after 1-3 weeks of use.

How do I prescribe PrEP?

1. All individuals seeking to start PrEP need to have baseline HIV testing performed to be sure they are in fact HIV negative. The fourth generation HIV assay has a window period of median 3 weeks, and it is important to make sure that recent high risk sexual exposures are taken into account when you order the test. In addition, in order to prescribe PrEP in BC, an updated HIV test (within 15 days) is required for the PrEP prescription, and it is therefore critical to ensure that the timing of laboratory work is acceptable for this requirement.
2. Other baseline recommended testing includes renal function (creatinine/ glomerular filtration rate, urinalysis).
3. Hepatitis B testing is also recommended. As TDF/FTC is active against hepatitis B it is important to establish that there is no evidence of chronic active hepatitis B infection (positive HBV Surface Antigen). While it is possible to use PrEP in someone with active hepatitis B infection, monitoring would be required, and there would be a risk of hepatitis B flare if PrEP were to be discontinued without making a plan for hepatitis B therapy. Individuals with chronic HBV should be seen in consultation by a physician experienced in managing PrEP in this context.
4. Baseline testing for sexually transmitted infections should be performed based on reported sexual exposure (first void urine, throat and rectal swabs for gonorrhea/chlamydia NAT testing).
5. Regular testing for hepatitis C infection is recommended, and although it is not specifically required by PrEP guidelines, baseline evaluation for hepatitis A status to see if vaccination is required may be warranted.
6. The PrEP prescription form is available from the BC CfE website (http://www.cfenet.ubc.ca/hiv-pre-exposure-prophylaxis-prep/documents) and an initial 30-day supply is provided (44 days for individuals outside of Vancouver where shipping of medications to the prescribing physician’s office is required).
7. Repeat HIV and renal function testing are then performed after 3 weeks on PrEP, and if there are no major side effects, PrEP can be renewed for 90 days.  Pre-printed laboratory forms are also available on the website.
8. Quarterly assessment for adherence, and laboratory testing of HIV status, renal function and screening for sexually acquired infections is recommended.
9. The BC CfE website hosts local clinical guidelines, and clinical tools to guide you in prescribing PrEP, including an assessment tool and pre-printed laboratory requisitions for baseline, one month and quarterly screening, as well as educational resources (http://education.cfenet.ubc.ca/).
10. Instructions for how to obtain the medication can be printed from the website and given to the client (from St. Paul’s pharmacy if they reside within Vancouver or from a designated physician’s office outside of Vancouver).
11. A quick checklist for providers is included in Table One.

References

1. British Columbia Centre for Excellence in HIV/AIDS. HIV Monitoring Quarterly Report for Vancouver Coastal Health. http://stophivaids.ca/qmr/2018-Q2/#/vcha. Published Second Quarter 2018. Accessed October 16, 2018. (View)
2. 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):2587-2599. DOI: 10.1056/NEJMoa1011205. (View)
3. McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet. 2016;387(10013):53-60. DOI: 10.1016/S0140-6736(15)00056-2. (View)
4. Molina JM, Capitant 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. DOI: 10.1056/NEJMoa1506273. (View)
5. Volk JE, Marcus JL, Phengrasamy T, et al. No new HIV infections with increasing use of HIV preexposure prophylaxis in a clinical practice setting. Clin Infect Dis. 2015 Nov 15;61(10):1601-1603. DOI: 10.1093/cid/civ778. (View)
6. US Public Health Service. Pre-exposure prophylaxis for the prevention of HIV infection in the United States – 2017 Update. A clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf. Updated 2017. Accessed October 17, 2018. (View)
7. Tan DHS, Hull MW, Yoong D, et al. Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis. CMAJ. 2017;189(47):E1448-E1458. DOI: 10.1503/cmaj.170494. (View)
8. Smith DK, Pals SL, Herbst JH, Shinde S, Carey JW. Development of a clinical screening index predictive of incident HIV infection among men who have sex with men in the United States. J Acquir Immune Defic Syndr. 2012;60(4):421-427. DOI: 10.1097/QAI.0b013e318256b2f6. (View with CPSBC or UBC)

Table One Pre-Exposure Prophylaxis Prescriber Checklist

Laboratory Requisitions (http://www.cfenet.ubc.ca/publications/centre-documents/prep-lab-requisition-forms)

 ¹   HIV Ab/Ag EIA, ALT, AST, CBC, creatinine/GFR, HAV IgG, HBV Serology (HBV SAb, HBV SAg, HBV core antibody), HCV antibody, RPR, urinalysis, urine ACR, urine gonorrhea and chlamydia NAT. For timely access to PrEP these should be ordered prior to first consultation.  ²HIV Ab/Ag EIA, creatinine/GFR, urinalysis, urine ACR, urine GC and Chlamydia  ³ HIV Ab/Ag EIA, creatinine/GFR, RPR, urinalysis, urine ACR, urine GC and Chlamydia NAT q 3 months x 1 year. HCV Antibody q 12 months. ⁴ Recommended coverage can range from two days to 28 days, depending on duration of PrEP use, and type of exposure.

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