Providing HIV preexposure prophylaxis

Identifying individuals at risk of acquiring HIV

Individuals who are HIV negative and at elevated risk of HIV acquisition can be identified by taking a detailed sexual and drug use history. Both past and anticipated future risk should be considered. A trauma-informed, individualized approach should be followed based on sex, culture, and ethnic background. Prescribers may use the HIV Incidence Risk Index for MSM (HIRI-MSM) assessment tool to estimate an individual’s HIV risk.⁵ Validated in a Vancouver-based study, the HIRI-MSM tool found that scores of 10 or higher were associated with a 2% per year incidence of HIV, while scores of 25 or higher represented a 7% per year incidence of HIV.⁶ A Canadian guideline on HIV PrEP endorses the HIRI-MSM assessment tool and considers PrEP to be indicated for MSM with a risk score of 11 or greater.² A low HIRI-MSM score means HIV acquisition is unlikely; however, PrEP may still be offered if benefits outweigh risks for the individual.

In addition, an individual may be at increased risk of HIV acquisition if they have required nonoccupational post-exposure prophylaxis (approximately 7% per year incidence of HIV) or have a history of sexually transmitted infections (STIs) (approximately 5% per year incidence of HIV).^6,7

Case description

Thomas (a pseudonym), a 31-year-old man, is new to your family practice. Thomas tells you he recently moved to the area, does not have any known medical diagnoses, and considers himself healthy. You seek permission to ask Thomas some questions about his sexual history as part of your routine care. Thomas agrees to this.

Doctor: “To start with, do you have any questions about your sexual health?”

Thomas: “It’s been a while since I had an STI test. Should I get tested more often now that my boyfriend and I decided to have an open relationship? We know we should wear condoms, but it doesn’t always happen.”

Doctor: “I recommend STI screening at least every 3 months given that you are sexually active. Since you have male partners, can I ask you some questions about your HIV risk? This will help me determine if a medication to prevent HIV transmission is worth considering, since many men underestimate their HIV risk.”

You use the HIRI-MSM assessment tool, and based on Thomas’ age (31 years, score of 5), number of male sexual partners (6 to 10 partners, score of 4), condomless receptive anal sex (1 or more times, score of 10), and use of poppers (alkyl nitrites; score of 3), you calculate his cumulative score to be 22. According to a Canadian guideline on HIV PrEP,² he has an indication for PrEP and could consider this strategy to protect himself from acquiring HIV.

Bringing evidence to practice: combination medications

Currently, there are 2 medications indicated for the prevention of HIV in MSM in Canada (Table 1). In a randomized controlled trial, participants receiving a combination of 200 mg–300 mg emtricitabine– tenofovir disoproxil fumarate daily reduced the relative incidence of HIV by approximately 50% in males at high risk compared with placebo over 1.2 years (event rate=3% vs 5.8%; number needed to treat=36; hazard ratio=0.53, 95% CI 0.36 to 0.78).⁸ Relative risk was reduced by 92% (95% CI 40% to 99%) in a subgroup analysis of those with detectable drug levels, highlighting the importance of adherence.⁸ The prodrug formulation emtricitabine– tenofovir alafenamide, taken daily, was found to be non-inferior to emtricitabine–tenofovir disoproxil fumarate taken daily for prevention of HIV in MSM.⁹ Efficacy was also demonstrated in an open-label pilot study involving MSM.¹⁰ Preexposure prophylaxis taken daily is an effective strategy to decrease the risk of HIV transmission.

Preexposure prophylaxis is generally well tolerated. In randomized controlled trials, only 2% of participants permanently discontinued therapy because of adverse events.^8,9 Individuals may experience nausea with PrEP, especially within the first 4 weeks of therapy (event rate=9% vs 5%; number needed to harm=25; P<.0021).⁸ However, tolerance developed after 1 to 2 weeks, with nausea rates decreasing similar to placebo.⁸ Some individuals may experience diarrhea (4% to 16%) or headache (2% to 4%); these adverse events were similar to placebo.^8,9

Preexposure prophylaxis does not usually lead to more risky sexual practices. Multiple trials have shown no difference in STI incidence for participants taking PrEP compared with placebo.^8,10 One trial found a reduction in participants’ number of receptive anal intercourse partners from approximately 12 partners to 6 partners, and an increase in condom use from approximately 50% to 75%.⁸

Emtricitabine–tenofovir disoproxil fumarate may impact kidney function (approximately 1 mL/min/year estimated glomerular filtration rate [eGFR] decrease compared with placebo) and may minimally decrease bone mineral density.² Both changes are usually reversible upon discontinuation. Experts suggest minimizing nephrotoxins such as nonsteroidal anti-inflammatory drugs, avoiding volume depletion, and managing kidney-related comorbidities (eg, hypertension and diabetes).² Emtricitabine–tenofovir alafenamide appears to have less impact on kidney and bone surrogate biomarkers and may be an alternative for those with an eGFR less than 60 mL/min or previous fracture.⁹

When PrEP is initiated, kidney function testing, along with all other investigations outlined in Table 2, are required at baseline and periodically to ensure ongoing effectiveness and safety. Baseline bone mineral density testing is not recommended unless there is another compelling indication.^2,3,11 Individuals with an eGFR less than 60 mL/min, with a history of fractures, or who are pregnant should be referred to an HIV or infectious disease specialist for further management.

Back to Thomas

You discuss Thomas’ risk of acquiring HIV and explain the benefits of PrEP. Thomas is interested but does not know much about PrEP beyond having a few friends who currently take it. You show Thomas a PrEP infographic (available from CFPlus^*) and provide information about PrEP.

Doctor: “PrEP, or preexposure prophylaxis, is a way to prevent you from getting HIV. It is 1 pill that contains 2 medications typically taken once daily. This is called the continuous dosing method. The short-term and long-term effects of this medication are well known because it has been used for years as a component of HIV treatment. In studies, it has been shown to be effective, safe, and well tolerated when taken as prescribed.”

Thomas: “I’m still not sure. Can you tell me about the side effects?”

Doctor: “Most people do not have side effects, but some may experience mild stomach upset or headaches after starting. If these occur, they typically resolve in about 1 to 2 weeks as you adjust to the medication. If you take PrEP daily for many years, it may minimally impact kidney function and bone mineral density. Because of this, we check your kidney function before starting, as well as every 3 months along with HIV tests. Monitoring bone density is not required for most individuals since this effect occurs gradually over many years and appears to be reversible when PrEP is discontinued.”

See Box 1 for further counseling tips. After your discussion, Thomas agrees to start PrEP and you order bloodwork as per Table 2.

Follow-up via telephone, 1 week later

Thomas’ baseline bloodwork results are within the normal range and he is HIV negative. He is advised to initiate the medication for at least 7 days before sexual exposure to be fully protected, to monitor for HIV seroconversion illness, and to avoid long-term nonsteroidal anti-inflammatory drug use (Box 1). A 1-month prescription for emtricitabine–tenofovir disoproxil fumarate is sent to the pharmacy (Table 1), and Thomas is asked to do repeat bloodwork 1 week before running out of his prescription (Table 2).

Follow-up in office, 1 month later

Thomas had loose bowel movements after starting PrEP, but this resolved after 2 days. His 1-month bloodwork results were within normal limits, including kidney function, and he is confirmed HIV negative. He tells you he is less anxious about acquiring HIV during sexual encounters since starting PrEP. He has heard from some friends that they only take PrEP when they need to (or on demand) and is wondering if he could switch.

Bringing evidence to practice: continuous versus on demand

Both continuous daily and on-demand dosing methods are evidence-based options for MSM. On-demand dosing requires a loading dose (2 tablets of 200 mg–300 mg emtricitabine–tenofovir disoproxil fumarate given as 1 dose) 2 to 24 hours before sexual activity, followed by 1 tablet daily until 2 days after the last sexual activity (Table 1 and CFPlus^*). In a randomized controlled trial, this dosing strategy reduced the incidence of HIV by 86% in high-risk MSM compared with placebo (event rate=1% vs 7%; hazard ratio=0.86; 95% CI 0.40 to 0.98).¹² Study drug was not detected in the participants who acquired HIV, and the trial was stopped early after 9.3 months for benefit.¹² More participants taking on-demand dosing experienced gastrointestinal adverse events compared with placebo (event rate=14% vs 5%; number needed to harm=12); this was thought to be related to the loading dose.¹² There was also more serum creatinine level elevation with emtricitabine–tenofovir disoproxil fumarate compared with placebo (18% vs 10%; P=.03), but none of these events led to drug discontinuation.¹² There was no difference in fractures between groups.¹²

Usually, the continuous daily dosing method is prescribed initially to determine an individual’s tolerance of PrEP, and then the on-demand dosing method can be considered based on an individual’s adherence, preference, and other factors. Continuous daily dosing of PrEP has a larger body of evidence supporting its on-label use in MSM and can be beneficial for those who prefer the habit of daily administration or who have regular sexual activity. Although it is an off-label use, on-demand dosing is endorsed by a Canadian guideline and can offer less pill burden with less drug exposure for those with predictable sexual activity.² However, some individuals experience more gastrointestinal symptoms from the on-demand loading dose. This method should be used with caution and in consultation with infectious disease specialists for hepatitis B–positive individuals as continuous daily dosing is often preferred. Investigation and monitoring (Table 2) remain the same for both continuous daily and on-demand dosing methods.

Case resolution

You and Thomas discuss both PrEP dosing methods.

Doctor: “The daily method is better for those who have a hard time remembering to take medications, since it would be a part of your routine. It also provides continuous protection if you have sex often or have sexual encounters that aren’t planned. The on-demand method is when you take 2 tablets of PrEP 2 to 24 hours before sex, followed by 1 tablet daily until 48 hours after the last time you have sex. It is a bit more difficult to remember but may be a better option if you have sex infrequently and more predictably. Both methods work well.”

Using shared decision making, Thomas decides to continue with once-daily dosing of PrEP as this will be easiest for him to remember. He also anticipates new partners in the future and unpredictable sexual encounters. A 3-month prescription is given to him with instructions to complete bloodwork and STI screening 1 to 2 weeks before his next follow-up appointment in 3 months. Review of these investigations is required before providing the next renewal of the 3-month prescription. If his sexual practices change, his risk of HIV acquisition can be re-assessed at his next follow-up visit. Figure 1 summarizes the management of PrEP.

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Figure 1.

PrEP management timeline