11.4 HIV Prevention & Treatment, Viral Hepatitis, Tuberculosis & Fungal Infections
Key Takeaways
Integrase inhibitors chelate polyvalent cations, so separate them from calcium, iron and antacids (before by 2 hours or after by 6) unless the monograph allows co-administration with food.
HIV PEP starts as soon as possible within 72 hours and lasts 28 days; PrEP with TDF/emtricitabine needs HIV, renal, hepatitis B and STI testing every 3 months.
Screen for hepatitis B before rituximab, other potent immunosuppressants and hepatitis C antivirals because of the risk of HBV reactivation.
Canadian first-line treatment for TB infection is 4 months of rifampin or 12 weekly doses of rifapentine plus isoniazid, after active TB is ruled out.
Rifampin is a potent enzyme inducer, and fluconazole raises warfarin effect even after a single 150 mg dose.
HIV Prevention & Treatment, Viral Hepatitis, Tuberculosis & Fungal Infections
These infections share three exam themes: prevention (PrEP, PEP, vaccination, latent TB treatment), drug interactions (boosters, rifamycins, azoles, polyvalent cations), and adherence and monitoring over long courses. Community pharmacists dispense most of these therapies and often catch the interactions first.
1. HIV Treatment Principles
- Start antiretroviral therapy (ART) for everyone with HIV, as soon as possible. A durably undetectable viral load prevents sexual transmission ("Undetectable = Untransmittable").
- Usual initial regimens combine an integrase strand transfer inhibitor (INSTI) with two nucleoside reverse transcriptase inhibitors. Examples: bictegravir/emtricitabine/tenofovir alafenamide (one tablet daily), or dolutegravir plus two NRTIs. Dolutegravir/lamivudine is an option for selected patients without hepatitis B.
- HLA-B*5701 testing is required before abacavir, because carriers are at high risk of a hypersensitivity reaction. Never rechallenge after a suspected reaction.
- Tenofovir: tenofovir disoproxil fumarate (TDF) carries more renal and bone toxicity than tenofovir alafenamide (TAF). Monitor creatinine and urine protein.
High-Yield ART Interactions
| Interaction | Mechanism | Management |
|---|---|---|
| INSTIs + polyvalent cations (calcium, iron, magnesium, aluminum, zinc, antacids, multivitamins) | Chelation in the gut lowers INSTI absorption | Take dolutegravir or bictegravir 2 hours before or 6 hours after cation products. With food, iron or calcium may be taken at the same time as dolutegravir (follow the monograph) |
| Boosters (ritonavir, cobicistat) + CYP3A4 substrates | Strong CYP3A4 inhibition | Avoid simvastatin and lovastatin; reduce doses of others. Inhaled or intranasal fluticasone and budesonide can cause Cushing's syndrome. Midazolam, some antiarrhythmics and ergots are contraindicated |
| Rifampin + most ART | Strong induction lowers ART levels | Use rifabutin with dose changes, or adjust the INSTI dose (dolutegravir twice daily) under specialist direction |
| Dolutegravir + metformin | Dolutegravir raises metformin levels | Limit the metformin dose and monitor |
2. HIV Pre- and Post-Exposure Prophylaxis
- PrEP (pre-exposure prophylaxis):
- Regimen: TDF/emtricitabine once daily. For men who have sex with men, "on-demand" (2-1-1) dosing is an alternative: two tablets 2 to 24 hours before sex, then one tablet 24 and 48 hours after the first dose.
- Before starting: a negative HIV test, creatinine, hepatitis B status (stopping TDF/FTC can trigger an HBV flare), STI screening and pregnancy testing.
- Follow-up: repeat HIV and STI testing every 3 months.
- PEP (post-exposure prophylaxis):
- Timing: start as soon as possible, ideally within 2 hours and no later than 72 hours after a high-risk exposure.
- Regimen: a 3-drug course for 28 days (for example, bictegravir/FTC/TAF, or TDF/FTC plus dolutegravir or raltegravir).
- Follow-up: baseline and follow-up HIV testing. Check hepatitis B and C status and tetanus need after needlestick injuries.
3. Viral Hepatitis
- Hepatitis A: inactivated vaccine for travellers, people with chronic liver disease, men who have sex with men, and people who use drugs.
- Hepatitis B:
- Vaccination: routine childhood vaccination, plus at-risk adults (3-dose series; a 2-dose adjuvanted adult vaccine also exists).
- Chronic HBV: treated with tenofovir (TDF or TAF) or entecavir. Treatment is usually long-term. Stopping abruptly can cause a severe hepatitis flare.
- Reactivation risk: screen for HBV before rituximab, other potent immunosuppressants, chemotherapy, and hepatitis C direct-acting antivirals, all of which can reactivate HBV.
- Hepatitis C: curable in more than 95% of patients with pangenotypic direct-acting antivirals (DAAs):
- Sofosbuvir/velpatasvir for 12 weeks.
- Glecaprevir/pibrentasvir for 8 weeks in most treatment-naive patients without decompensated cirrhosis.
- Interaction red flags: amiodarone with sofosbuvir can cause severe bradycardia. Acid suppressants reduce velpatasvir absorption, so PPIs need specific timing or are avoided. Rifampin, carbamazepine and St. John's wort reduce DAA levels. Glecaprevir/pibrentasvir is not used with ethinyl estradiol-containing products (ALT elevations).
- Cure is confirmed by an undetectable HCV RNA 12 weeks after therapy (SVR12). Reinfection is possible, so harm-reduction counselling continues.
4. Tuberculosis
TB Infection (Latent TB) — Canadian Tuberculosis Standards, 8th Edition
- First-line: 3HP (once-weekly rifapentine plus isoniazid for 12 doses) or 4R (daily rifampin for 4 months).
- Alternatives: if rifamycins cannot be used, 9H (daily isoniazid for 9 months) is preferred, and 6H if 9H is not possible.
- Rifapentine is not marketed in Canada. Practitioners obtain it through federal urgent public health need provisions or the Special Access Program.
- Rule out active TB before treating TB infection, using symptoms and a chest X-ray.
Active TB
- Regimen: standard drug-susceptible therapy is isoniazid, rifampin, pyrazinamide and ethambutol for 2 months, then isoniazid and rifampin for 4 months, preferably as directly observed therapy.
- Isoniazid: hepatotoxicity and peripheral neuropathy. Give pyridoxine (vitamin B6) to patients at risk (diabetes, alcohol use, malnutrition, pregnancy, HIV, CKD).
- Rifampin: orange-red body fluids (stains soft contact lenses) and strong CYP3A4, CYP2C9 and P-gp induction. It lowers the levels of hormonal contraceptives, warfarin, DOACs, methadone, azoles, many antiretrovirals and immunosuppressants, so check every interaction.
- Ethambutol: optic neuritis, so check visual acuity and colour vision.
5. Fungal Infections
| Infection | Treatment | Key counselling |
|---|---|---|
| Vulvovaginal candidiasis | Fluconazole 150 mg once orally (Schedule III), or a topical azole for 1 to 7 days | Pregnancy: topical azole for 7 days, not oral fluconazole. Refer if recurrent (4 or more episodes a year), first episode, or symptoms suggest another cause |
| Oral thrush | Nystatin suspension (swish and swallow), or fluconazole for moderate disease | Rinse after inhaled corticosteroids; check dentures |
| Tinea pedis and corporis | Topical terbinafine (1 to 2 weeks) or azoles (2 to 4 weeks) | Continue for 1 to 2 weeks after the skin clears; keep feet dry |
| Onychomycosis | Oral terbinafine 250 mg daily for 6 weeks (fingernails) or 12 weeks (toenails); topical efinaconazole for mild disease | Confirm the diagnosis first; baseline liver tests; full nail regrowth takes 12 to 18 months |
Caution
Azole interactions: fluconazole inhibits CYP2C9 and CYP3A4 and markedly raises warfarin INR, even after a single 150 mg dose. It also increases sulfonylurea and phenytoin levels. Itraconazole and ketoconazole are strong CYP3A4 inhibitors.
A patient taking bictegravir/emtricitabine/tenofovir alafenamide once daily in the morning starts calcium carbonate 500 mg twice daily for osteoporosis prevention. Which counselling is most appropriate?
Stop the calcium, because calcium supplements are contraindicated with HIV therapy.
Take all three products together with breakfast so they are not forgotten.
Separate them: take the antiretroviral at least 2 hours before the calcium, or take them together with food as the product monograph allows.
Switch the calcium to bedtime only, because calcium reduces antiretroviral absorption only when both are taken in the morning on an empty stomach.
A 26-year-old presents to a pharmacy 30 hours after a condom broke during sex with a partner known to have HIV whose viral load is unknown. Which statement best describes HIV post-exposure prophylaxis (PEP)?
Start PEP now (within 72 hours) for 28 days, with HIV testing at baseline and follow-up.
A single dose of tenofovir/emtricitabine now is sufficient as PEP after a one-time exposure.
PEP is only indicated after occupational needlestick injuries, not after sexual exposures.
PEP is no longer useful because more than 24 hours have passed.
Under the Canadian Tuberculosis Standards, which regimen is a recommended first-line option for tuberculosis infection (latent TB) in an adult with no drug interaction concerns?
Isoniazid, rifampin, pyrazinamide and ethambutol for 2 months.
Isoniazid daily for 1 month.
Ethambutol daily for 9 months.
Rifampin daily for 4 months.
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