HIV Infection: Prevention

Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) use antiretroviral drugs to prevent HIV acquisition in an HIV-negative person, rather than to treat established infection — the subject of a separate chapter. PrEP is taken before an exposure and continued through an ongoing period of risk; PEP is a short course started after a specific exposure, and is further described by setting as occupational PEP (a workplace exposure, e.g. a needlestick) or non-occupational PEP (nPEP, following a sexual exposure or shared injection equipment) — current Canadian guidance uses largely the same drug regimens and timelines for both settings. Every prophylaxis decision rests on two inputs: the type of exposure and the likelihood that the source person has transmissible HIV infection.^[1] Because starting or continuing PrEP during an undiagnosed acute HIV infection can select for drug-resistant virus, confirming a current negative HIV status is a precondition for every strategy in this chapter, not an afterthought.

PrEP, PEP, and nPEP at a glance

Recognizing acute HIV seroconversion

Acute retroviral syndrome can occur in anyone with a recent HIV exposure, including a patient already taking PrEP who acquired HIV despite it, or a patient who was in the undiagnosed window when PrEP was started. It is nonspecific and easy to mistake for a viral upper respiratory illness or mononucleosis, so ask about it directly in anyone being considered for, or already using, PrEP or PEP/nPEP.

• Fever
• Rash
• Sore throat (pharyngitis)
• Oral ulcers
• Fatigue and malaise
• Night sweats
• Myalgia and arthralgia (muscle and joint pain)
• Lymphadenopathy (swollen lymph nodes)
• Loss of appetite

Recognizing a qualifying exposure for PEP/nPEP

These tiers describe the exposure act itself and are combined with the source person's HIV risk category (see Assessment & Diagnosis) to decide whether PEP/nPEP is indicated.^[1]

• Anyone who requests PrEP should be offered it, regardless of whether specific risk factors are elicited — self-assessed risk is a sufficient indication on its own, since a targeted risk-factor checklist can underestimate a person's actual risk.^[1]
• Clinicians should raise PrEP with every sexually active patient at least once, since at-risk individuals are often missed when screening relies only on a patient volunteering risk information.^[2]
• Condomless anal intercourse in the past 6 months in a man who has sex with men or a transgender woman, together with any of: infectious syphilis or a rectal bacterial STI, recurrent use of nPEP, or an ongoing sexual relationship with a partner who has HIV infection with a substantial risk of transmissible virus.
• Condomless vaginal/front-hole or anal intercourse with a partner known to have HIV infection with a substantial or low-but-nonzero (not negligible) risk of transmissible virus, in a person having heterosexual sex.
• Sharing injection drug-use equipment with a person who has a non-negligible risk of HIV infection, or otherwise meeting the sexual-risk criteria above.
• A sexually transmitted infection diagnosed within the past 6-12 months.
• Recurrent nPEP use — this specifically signals ongoing risk and should prompt a PrEP discussion rather than repeated PEP courses.
• Transgender individuals face a disproportionately increased HIV risk driven by intersecting social and structural factors and should be assessed for PrEP based on individual risk rather than a single behavioural checkbox.
• Adolescents with any of the above risk factors may also be candidates for PrEP, with more frequent follow-up to support adherence.

Categorizing the source person's HIV risk

Whether PEP/nPEP is indicated, and whether PrEP should be offered, both depend on how likely the source partner is to have transmissible HIV infection.^[1]

PrEP candidacy assessment

History: sexual history, including gender identity, sexual orientation, sexual behaviours and anatomy, drug use, number/type of partners, and condom use; substance use, including methamphetamine or other drug use during sex; STI history within the past 6-12 months; and prior nPEP use.

Physical exam: screen for signs or symptoms of acute HIV infection (see Recognize the Condition) and for signs of any STI.

Baseline labs: an HIV test — a 4th-generation combination antibody/antigen assay is preferred — confirmed negative shortly before starting; syphilis serology; chlamydia and gonorrhea screening by urine NAAT plus throat and rectal swabs as indicated by exposure sites; hepatitis A, B, and C serologies, with vaccination offered against hepatitis A and B if nonimmune; renal function (serum creatinine/creatinine clearance) and urinalysis; and a pregnancy test for anyone of childbearing potential.

Hepatitis B or C infection is not a contraindication to PrEP, but liver function should be monitored for hepatitis B reactivation if emtricitabine/tenofovir DF or emtricitabine/tenofovir AF (both active against hepatitis B) is later discontinued — neither is active against hepatitis C.

PEP/nPEP assessment

Assess exposure timing (indicated within 72 hours) and exposure type (see Recognize the Condition); for nPEP, distinguish consensual from non-consensual exposure and offer sexual assault support services when applicable. Where possible, assess the source person's HIV status without delaying PEP/nPEP initiation — if the source is later confirmed HIV-negative, PEP/nPEP can be stopped and no further HIV follow-up testing of the exposed person is required. If the source has known HIV infection and consents to disclosure, obtain a viral load and resistance history to guide regimen selection.

Baseline labs for the exposed person: an HIV test (4th-generation combination assay, plus a point-of-care test if available); hepatitis B serology (surface antigen, surface antibody, core antibody), hepatitis C antibody, and alanine aminotransferase; a pregnancy test where appropriate; and renal function with a complete blood count if PEP/nPEP is being considered.

Do not delay initiation of PEP/nPEP while awaiting any test result.

When prophylaxis is not indicated

PrEP is not indicated when both the exposure type and the source person's risk category are negligible or none. PEP/nPEP is not indicated after a low-risk exposure, or when the source meets the U=U criteria above.

• Prevent HIV acquisition in an HIV-negative individual with ongoing or recent exposure risk.
• Avoid initiating or continuing prophylaxis in someone with undiagnosed acute or established HIV infection, which risks selecting drug-resistant virus.
• Achieve and sustain the level of adherence the chosen regimen needs for its protective effect.
• Identify and treat any coexisting STI, and offer hepatitis A/B vaccination where indicated.
• Transition anyone with recurrent PEP/nPEP need onto PrEP without a gap in protection.

• Offer HIV/STI prevention counselling, condoms, and regular testing to every individual, regardless of which prophylactic strategy is chosen — PrEP and PEP/nPEP protect against HIV only, not other STIs or pregnancy.
• Regular STI testing is specifically recommended for anyone on PrEP, since an increased rate of other STIs has been observed among some PrEP users.
• Offer proven harm-reduction services to people who inject drugs, including access to sterile needles, syringes, and other injection equipment, and opioid agonist therapy.
• Screen for and address comorbid mental health and substance use concerns, and unstable housing, food, or financial insecurity, as part of a comprehensive prevention strategy — these barriers strongly affect adherence and follow-up.
• For nPEP following a non-consensual exposure, offer sexual assault support services alongside the standard medical assessment.
• Counsel on secondary-transmission precautions during PEP/nPEP, and until the 3-month HIV test is confirmed negative: barrier contraception, avoiding blood or tissue donation, and deferring pregnancy or breastfeeding where feasible.
• Build adherence support proactively into every visit — reminder tools, pharmacist-led follow-up, and addressing drug coverage or access barriers — since the protective effect of every PrEP option is directly tied to how consistently it is taken or received on schedule.^[2]

Pregnancy

For PrEP, emtricitabine/tenofovir DF has the most pregnancy safety data and is the preferred agent if PrEP is used in pregnancy, with no dose adjustment required. For PEP/nPEP, preferred regimens in pregnancy are emtricitabine/tenofovir DF plus dolutegravir 50 mg once daily, or plus raltegravir 400 mg twice daily (the standard, not the once-daily high-dose, formulation, given a lack of pregnancy data for the high-dose tablet), or plus ritonavir-boosted darunavir 800/100 mg once daily — once-daily darunavir/ritonavir dosing is considered adequate specifically for the lower, prophylactic viral burden of PEP/nPEP, even though twice-daily dosing is used to treat established HIV infection in pregnancy. Lamivudine/zidovudine may substitute for emtricitabine/tenofovir DF in pregnancy. Avoid elvitegravir/cobicistat-containing regimens in pregnancy given the risk of subtherapeutic levels as pregnancy progresses.

Breastfeeding

PrEP may be used while breastfeeding where the benefit — avoiding maternal HIV acquisition, which carries a very high risk of transmission to the infant if acquired during lactation — outweighs the risk; emtricitabine and tenofovir DF are both transferred into breast milk at low-to-moderate levels. For PEP/nPEP, weigh the same risk-benefit through shared decision-making; pausing breastfeeding is sometimes advised specifically when a higher-risk exposure requires nPEP.

Pediatrics and adolescents

Daily oral PrEP, cabotegravir, and lenacapavir are all authorized from 12 years of age and a minimum body weight of 35 kg — the same dual age-and-weight threshold applies across all three, not just the injectables. On-demand dosing is not established in adolescents; use daily dosing in this age group. Adolescents may need more frequent follow-up visits to support adherence than adults.

Renal impairment

PrEP should not be used at a creatinine clearance under 30 mL/min. Emtricitabine/tenofovir DF should not be used at a creatinine clearance under 60 mL/min; emtricitabine/tenofovir AF may be used down to 30 mL/min, a practical advantage in mild-to-moderate renal impairment. Cabotegravir and lenacapavir require no dose adjustment for renal impairment.

Hepatitis B or C coinfection

Neither is a contraindication to PrEP. Because emtricitabine/tenofovir DF and emtricitabine/tenofovir AF are both active against hepatitis B, stopping either requires monitoring for a hepatitis B flare; neither drug is active against hepatitis C.

People who inject drugs

PrEP is indicated per the sexual- or equipment-sharing risk criteria above; combine PrEP with harm-reduction services rather than treating them as alternatives to each other.

Transgender individuals

Elicit the patient's own anatomy and their partners' anatomy directly and non-judgmentally to select an appropriate regimen — PrEP drug concentrations and adherence requirements differ meaningfully between rectal and vaginal/front-hole tissue, so regimen and dosing-schedule choice (for example, avoiding on-demand dosing or emtricitabine/tenofovir AF for vaginal/front-hole-only risk) must reflect the individual's actual anatomy and exposure type, not an assumption based on gender identity.^[10]

PrEP

Consider a tolerability/adherence check at 30 days, then formal reassessment at least every 3 months while on daily oral or on-demand PrEP: an HIV test, renal function (serum creatinine at 30 days, then every 3 months while on a tenofovir DF-containing regimen), an STI screen (syphilis, chlamydia, gonorrhea), and a pregnancy test where appropriate; repeat hepatitis C antibody (and a hepatitis B screen if nonimmune) annually. Do not issue a PrEP prescription beyond a 90-day supply without reconfirming a negative HIV status first.

For cabotegravir, confirm a negative HIV test before every injection and maintain the every-2-month injection schedule (a window of about 7 days on either side is acceptable). For lenacapavir, confirm a negative HIV test using a method sensitive enough to detect very recent infection before every dose, and maintain the every-26-week injection schedule.

Discontinuing oral PrEP: protection decreases over the 7-10 days following the last dose; a patient with a long history of adherent daily use may need only about 2 further days of dosing after their last exposure, while others (e.g. people who inject drugs, or women, given tissue-specific pharmacokinetics) may reasonably continue for up to 28 days by extrapolation from PEP data. HIV testing at 8 weeks after discontinuation is reasonable, since drug levels on PrEP can delay antibody detection. Discontinuing an injectable (cabotegravir or lenacapavir) requires bridging to another effective PrEP method, generally starting within about 2 months of the last injection and continuing for up to a year, given how long detectable drug levels persist.

PEP and nPEP

Reassess within 72 hours to confirm tolerability and adjust the regimen if source-person test results have since become available. Follow-up HIV testing at 6 weeks and 3 months after exposure reflects current, shortened guidance built around more sensitive HIV assays; extend testing to 6 months specifically if hepatitis C was acquired from the same exposure, given a risk of delayed HIV seroconversion in that setting.^[9] Hepatitis B and C serology are repeated per baseline results and exposure type. Repeat serum creatinine and a complete blood count at 2 weeks only if baseline results were abnormal or the patient is symptomatic — routine repeat toxicity labs are no longer required when baseline results are normal and the patient remains asymptomatic.^[9] Anyone who has needed nPEP more than once should be assessed for, and offered, PrEP — ideally starting immediately after completing the current 28-day nPEP course to avoid a gap in protection.

1. A new HIV-positive test, or symptoms of acute seroconversion, at any point on PrEP: stop PrEP immediately, obtain HIV RNA and resistance testing, and refer urgently for HIV treatment — do not continue a 1- or 2-drug PrEP regimen once infection is confirmed or strongly suspected.
2. Presenting beyond 72 hours after a high-risk exposure: PEP/nPEP is not routinely effective this late, but still complete risk-reduction counselling and baseline testing, and consider expert consultation for an exceptionally high-risk exposure rather than declining care entirely.
3. Reported nonadherence to daily oral PrEP: reinforce adherence support at every visit; if adherence remains a genuine, persistent barrier, consider switching to a long-acting injectable option rather than continuing an oral regimen the patient cannot reliably take.
4. Recurrent nPEP courses: this is itself a signal of ongoing risk — transition to PrEP as soon as the current course is complete, with a fresh baseline HIV-negative confirmation, rather than leaving a protection gap.
5. Known or emerging drug resistance in the source person, or intolerable adverse effects on the current regimen: obtain expert consultation for regimen adjustment rather than empirically substituting another agent.
6. Renal function declining below the threshold for the current PrEP agent: switch to an option compatible with the patient's current renal function (see Special Populations) rather than continuing the original agent unchanged.

• Starting or continuing PrEP without a current, confirmed negative HIV test, or without repeating testing when acute infection is suspected — the single highest-stakes error in this chapter.
• Prescribing on-demand ("2-1-1") dosing or emtricitabine/tenofovir AF for a patient whose risk is from receptive vaginal/front-hole intercourse — neither is supported for this population.
• Issuing a PrEP prescription beyond a 90-day supply without reconfirming HIV-negative status first.
• Delaying PEP/nPEP initiation to await source-person testing or baseline labs — start promptly and adjust later if needed.
• Missing that a patient has repeatedly needed nPEP without ever being offered PrEP.
• Stopping emtricitabine/tenofovir DF or AF in a patient with hepatitis B coinfection without monitoring for a hepatitis flare.
• Continuing routine toxicity labs (e.g. fixed-interval repeat CBC/creatinine) for an asymptomatic PEP/nPEP patient whose baseline results were normal — this is no longer required.
• Treating a missed or late long-acting injectable PrEP dose as a minor scheduling issue rather than a genuine protection gap that needs bridging and reassessment.
• Forgetting that PrEP and PEP/nPEP protect against HIV only — condoms, STI testing, and contraception still need separate attention.

How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Pediatric dosing for PrEP and PEP/nPEP is authorized only from 12 years of age (and, for the injectables, a minimum body weight) — it is not established below that threshold and should not be extrapolated without specialist input. Select any drug name to open its complete Pharmasist Drug Database page.

Coformulated NRTI/NtRTI combinations (PrEP daily/on-demand backbone; PEP/nPEP backbone)

Individual NRTIs/NtRTIs (PEP/nPEP alternative backbone components)

Used when the coformulated tablet above is not appropriate, e.g. for renal-impairment dose separation.

Long-acting injectable PrEP

Integrase inhibitors (PEP/nPEP 3rd agent)

Protease inhibitors (PEP/nPEP alternative 3rd agent, e.g. known/suspected source drug resistance)