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HIV Pre-Exposure Prophylaxis (PrEP)
PrEP is the use of antiretroviral medication by HIV-negative individuals to prevent acquiring HIV infection before potential exposure. It is one of the key pillars in the HIV prevention toolkit:
Who Should Receive PrEP?
PrEP should be considered - and per current CDC guidance can be offered to anyone who asks - in HIV-negative individuals with increased risk of HIV, including:
- Men who have sex with men (MSM) or men who have sex with men and women, particularly those not using condoms
- Transgender individuals
- People from - or whose partners are from - regions where HIV incidence is ≥3%
- Individuals who have traded sex for money, goods, or services
- Individuals with multiple sexual partners
- Individuals with a history of sexually transmitted infections (STIs)
- Individuals who have been or whose partners have been incarcerated
- People who inject drugs (PWID) - those sharing needles, syringes, or equipment
The CDC estimates approximately 1.2 million people in the United States are at "substantial" risk and should be counseled about PrEP.
(Goldman-Cecil Medicine, Table 3561; Harrison's, 22nd ed., Ch. 208)
Approved PrEP Regimens (as of 2025-2026)
There are now four approved PrEP options in the United States:
1. Daily Oral Tenofovir DF/Emtricitabine (TDF/FTC) - Truvada
- Dose: One tablet (TDF 300 mg + FTC 200 mg) once daily, with or without food
- Efficacy: ~99% effective with strict adherence
- Indication: All risk populations (sexual and PWID)
- Renal note: Not recommended if eGFR < 60 mL/min
- HBV note: TDF/FTC also treats HBV - stopping it can cause hepatitis flares in HBV-coinfected patients
2. Daily Oral Tenofovir Alafenamide/Emtricitabine (TAF/FTC) - Descovy
- Dose: One tablet (TAF 25 mg + FTC 200 mg) once daily
- Indication: MSM and transgender women; NOT approved for receptive vaginal sex
- Advantage: Better renal and bone safety profile vs. TDF/FTC
3. On-Demand (2-1-1) Dosing with TDF/FTC
- Dosing: 2 tablets 2-24 hours before sex, then 1 tablet 24 hours after, then 1 tablet 48 hours after the first dose
- Indication: MSM with planned sexual encounters, absent active HBV infection
- Status: FDA-approved labeling does not include this dosing; considered "off-label" but guideline-recommended (IAS-USA, IPERGAY trial data)
4. Long-Acting Injectable Cabotegravir (CAB-LA) - Apretude
- Dose: Cabotegravir 600 mg IM every 2 months (after 2 initiation injections 4 weeks apart)
- Indication: All sexual risk populations; first-line alongside oral options
- Efficacy: Similar or superior to daily oral TDF/FTC in trials (HPTN 083, HPTN 084)
- Advantage: No daily pill burden; preferred for those with adherence challenges
5. Twice-Yearly Subcutaneous Lenacapavir (LEN-SQ) - Sunlenca (newest, 2025)
- Dose: 927 mg subcutaneous injection every 6 months
- Mechanism: HIV capsid inhibitor (novel mechanism class)
- Efficacy: Phase 3 trial (PURPOSE 1) in South Africa and Uganda showed exceptional efficacy in cisgender women - essentially zero infections. PURPOSE 2 trial data in men, transgender women/men, and gender-nonbinary individuals are ongoing/emerging.
- 2025 CDC guidance: CDC MMWR 2025 issued formal recommendations for lenacapavir-SQ as HIV PrEP.
Baseline Evaluation Before Starting PrEP
| Test | Purpose |
|---|---|
| HIV test (4th-gen Ag/Ab) | Confirm HIV-negative status (mandatory) |
| Creatinine / eGFR | Baseline renal function (required for TDF-based PrEP) |
| Hepatitis B surface antigen (HBsAg) | Screen for active HBV (affects regimen choice and stopping decisions) |
| Hepatitis C antibody | Baseline screen |
| STI screening (gonorrhea, chlamydia, syphilis) | Baseline |
| Pregnancy test | For individuals who can become pregnant |
Monitoring on PrEP
| PrEP Type | HIV Testing Interval | Other Labs |
|---|---|---|
| Oral TDF/FTC or TAF/FTC | Every 3 months | Creatinine at 3 months, then every 6-12 months; STI screen q3-6 months |
| Injectable cabotegravir | Every 4 months (+ 1 month after first injection) | STI screen; renal not needed routinely |
| Lenacapavir SQ | Every 6 months | Per 2025 CDC guidance |
(UW HIV Medicine Core Concepts, 2025; 2021 CDC PrEP Guidelines)
Efficacy Summary
- Daily oral TDF/FTC (iPrEx trial and others): ~99% reduction in HIV acquisition with high adherence
- HPTN 083 (CAB-LA vs. TDF/FTC in MSM/TGW): 66% lower HIV incidence with cabotegravir
- HPTN 084 (CAB-LA vs. TDF/FTC in African women): 89% lower HIV incidence with cabotegravir
- PURPOSE 1 (lenacapavir in African women): 100% efficacy in the lenacapavir arm (zero infections)
- "Treatment as Prevention" (TasP / U=U): Virally suppressed partners pose effectively zero transmission risk (HPTN 052, PARTNER, Opposites Attract studies combined >125,000 sex acts without condom or PrEP)
(Harrison's Principles of Internal Medicine, 22nd ed., p. 1669)
Stopping PrEP
- Oral TDF/FTC: Continue for at least 7 days after last potential HIV exposure before stopping
- Cabotegravir-IM: Due to the long pharmacologic tail (drug persists for months after last injection), patients stopping injectable PrEP should transition to oral PrEP for a bridging period (typically oral TDF/FTC for ~12 months) to prevent resistant infection
- HBV co-infection: Do not stop TDF/FTC abruptly - risk of HBV flare
Special Populations
| Population | Notes |
|---|---|
| Adolescents | FDA-approved; AAP recommends offering PrEP to youth at substantial risk |
| Pregnancy / breastfeeding | TDF/FTC preferred (most safety data); TAF/FTC and CAB-LA data limited |
| Renal impairment | Avoid TDF-based PrEP if eGFR < 60; TAF/FTC safer; CAB-LA or lenacapavir require no renal adjustment |
| PWID | Oral TDF/FTC recommended; combine with needle exchange, addiction treatment |
PrEP vs. PEP - Key Distinction
| PrEP | PEP | |
|---|---|---|
| Timing | Before exposure (ongoing) | After exposure (emergency, within 72 hrs) |
| Duration | Ongoing while at risk | 28 days |
| Drugs | TDF/FTC, TAF/FTC, CAB-LA, LEN-SQ | 3-drug ART regimen x 28 days |
| Goal | Prevent acquisition in high-risk individuals | Post-exposure emergency prevention |
Recent Evidence (2024-2026)
- Systematic review on mHealth and PrEP adherence (PMID 40642253, 2025): Mobile health interventions significantly improve oral PrEP adherence and uptake among key populations.
- Interventions for oral PrEP adherence - network meta-analysis (PMID 38814406, 2024): Identifies effective adherence support strategies.
- Vaccination coverage in PrEP users - meta-analysis (PMID 42184839, 2026): Highlights the opportunity to use PrEP visits for catch-up vaccinations (HAV, HBV, HPV, meningococcal).
No recent systematic reviews contradict current guidelines. The emerging story is the superiority of long-acting formulations (CAB-LA, lenacapavir) over daily oral PrEP, particularly in populations with adherence challenges.
Sources:
- Harrison's Principles of Internal Medicine, 22nd ed. (2025), Ch. 208, p. 1669
- Goldman-Cecil Medicine, Table 356-1
- Harriet Lane Handbook, 23rd ed., Ch. 17
- 2021 CDC PrEP Clinical Practice Guideline
- 2025 CDC Lenacapavir PrEP Recommendations (MMWR 2025;74:541-9)
- UW HIV Medicine - PrEP Core Concepts
Heavy menstrual bleeding Prescription
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Heavy Menstrual Bleeding (HMB) - Prescriptions & Management
Definition: Excessive menstrual blood loss (classically >80 mL/cycle) that interferes with physical, social, emotional, or material quality of life. In practice, diagnosis is based on subjective impact rather than measured blood loss.
Step 1 - Investigate First
Before prescribing, exclude and treat underlying causes:
| Investigation | Purpose |
|---|---|
| CBC, ferritin | Anaemia, iron deficiency |
| Pelvic ultrasound (TVUS) | Fibroids, polyps, endometrial thickening |
| Thyroid function (TSH) | Hypothyroidism |
| Coagulation screen / VWF panel | Bleeding disorder (especially if HMB since menarche) |
| Pregnancy test | Exclude pregnancy-related bleeding |
| Endometrial biopsy | If >45 yrs, or risk factors for endometrial cancer |
Suspect a bleeding disorder if: HMB since menarche, family history of bleeding disorder, epistaxis, easy bruising, prolonged post-dental / post-surgical bleeding, postpartum haemorrhage.
Prescriptions by Severity
MILD HMB (adequate Hb, minimal impact on daily life)
Non-hormonal options (first line if no desire for contraception):
-
Tranexamic acid (antifibrinolytic) - FIRST-LINE non-hormonal agent
- Dose: 1.3 g (2 x 650 mg tablets) orally every 8 hours for up to 5 days, starting day 1 of menses
- Alternative dose cited: 3.9-4 g/day in divided doses for 4-5 days
- Reduces MBL by 26-50% vs. placebo; more effective than NSAIDs
- Do not use if history of thromboembolic disease
- Adverse effects: headache (55%), nausea (15%)
- Dose-reduce in renal impairment
-
NSAIDs (mefenamic acid / ibuprofen)
- Mefenamic acid: 500 mg orally three times daily from day 1 of menses through to end of period
- Ibuprofen: 400-600 mg orally three times daily during menses
- Reduces MBL by ~25-35% vs. placebo; also helps dysmenorrhea
- Less effective than tranexamic acid for HMB
- Note: NSAIDs are not effective for fibroid-related HMB (no reduction shown in fibroid-specific trials)
Supplemental Iron:
- Ferrous sulfate 325 mg (65 mg elemental iron) orally 1-3 times daily
- All patients with HMB should receive iron supplementation regardless of measured iron stores
MODERATE HMB / Chronic Management (hormonal options)
1. Levonorgestrel Intrauterine System (LNG-IUS) - Mirena - Most Effective Overall
- 52 mg LNG-IUS inserted by clinician
- Reduces MBL by 71-95%; superior to all oral medical therapies
- Also provides contraception; lasts 5-8 years
- Preferred long-term option per NICE and ACOG guidelines
- Adverse effects: irregular spotting initially, amenorrhoea in many after 12 months
2. Combined Oral Contraceptive Pill (COC)
- Dose: Low-dose COC (e.g., ethinyl estradiol 20-35 mcg + progestin) taken cyclically or continuously
- Reduces MBL by ~40-50%
- Provides contraception; also improves acne, dysmenorrhea
- Contraindications: Active thromboembolism, smoking >35 yrs, migraine with aura, liver disease, breast cancer
- For acute non-emergent situations: start with a 35 mcg ethinyl estradiol combination pill
3. Cyclic Progestin-Only (if COC contraindicated or declined)
- Medroxyprogesterone acetate (MPA): 5-10 mg orally once daily for 10-13 days every 1-2 months (luteal phase support)
- Norethindrone (norethisterone): 5 mg orally three times daily - used for acute/moderate bleeding, continue for 5-7 days
- Prevents endometrial hyperplasia from unopposed oestrogen
- Less effective than COC or LNG-IUS for reducing MBL overall
4. GnRH Agonists (e.g., Leuprolide, Nafarelin)
- Used mainly for fibroid-related HMB or pre-surgical management
- Reduces uterine/fibroid volume by 30-35% and controls bleeding
- Not for long-term use (>6 months) due to bone loss and menopausal side effects (hot flushes 78%, vaginal dryness 32%)
- Add-back therapy (low-dose oestrogen + progestin) can mitigate bone loss if extended use is needed
5. GnRH Antagonists (e.g., Elagolix/Relugolix - newer agents)
- Elagolix (Oriahnn): FDA-approved for HMB due to fibroids - 300 mg twice daily (with low-dose oestrogen/progestin add-back)
- More rapid onset than GnRH agonists; oral dosing
- 2025 FIGO guidance endorses GnRH antagonists for medical treatment of fibroid-related HMB
ACUTE / SEVERE HMB (Emergency Setting)
For acute heavy bleeding with haemodynamic instability:
1. Resuscitation first: IV fluids, blood products if Hb critical
2. IV Conjugated Equine Estrogen (CEE)
- 25 mg IV every 4-6 hours for up to 24 hours or until bleeding stops
- Rapidly stabilises endometrium
- Follow with oral progestin or COC after acute control
3. Tranexamic acid (acute)
- IV: 10 mg/kg (max 600 mg per dose) IV infusion
- Oral: 1.3 g every 8 hours for 5 days
4. High-dose Oral Norethisterone (Progestin)
- 5 mg orally three times daily for 1 week (acute non-emergent)
- OR MPA 20 mg three times daily (for acute heavy anovulatory bleeding)
5. COC for acute stabilisation
- 35 mcg ethinyl estradiol combination OCP - or medroxyprogesterone 20 mg three times daily for 1 week; then taper
6. Intrauterine tamponade (emergency)
- 26F Foley catheter inflated with 30 mL saline as a bridge to definitive management
Summary Table - Prescription Quick Reference
| Drug | Dose | Route | Timing | Use |
|---|---|---|---|---|
| Tranexamic acid | 1.3 g q8h | Oral | Days 1-5 of menses | Non-hormonal 1st line |
| Mefenamic acid | 500 mg TDS | Oral | During menses | Non-hormonal adjunct |
| Ibuprofen | 400-600 mg TDS | Oral | During menses | Non-hormonal adjunct |
| LNG-IUS (Mirena) | 52 mg | Intrauterine | Long-term (5-8 yr) | Most effective overall |
| COC (35 mcg EE) | 1 tablet OD | Oral | Cyclical/continuous | Hormonal 1st-line oral |
| Norethisterone | 5 mg TDS | Oral | Acute bleed x 5-7 days | Acute control |
| MPA | 5-10 mg OD | Oral | 10-13 days/month | Cyclic progestin |
| GnRH agonist | Per agent | SC/IN | Up to 6 months | Fibroids, pre-surgical |
| Elagolix | 300 mg BD | Oral | +add-back | Fibroid HMB |
| CEE IV | 25 mg q4-6h | IV | Acute, ≤24 hrs | Emergency bleed |
| TXA IV | 10 mg/kg (max 600 mg) | IV | Acute | Emergency bleed |
| Ferrous sulfate | 325 mg 1-3x/day | Oral | Daily | Adjunct (all patients) |
When to Refer / Consider Surgery
- Failure of medical management after 3-6 months
- Significant uterine fibroids or polyps on imaging
- Suspected endometrial pathology (biopsy/hysteroscopy needed)
- Desire for definitive treatment: endometrial ablation (non-fibroid), myomectomy (fibroid preservation), hysterectomy (definitive)
- Haemodynamic instability requiring emergency intervention
Sources:
- Berek & Novak's Gynecology - Ch. 9, pp. 409-415; Ch. 13, pp. 514-516
- Rosen's Emergency Medicine, Ch. 86, p. 1421
- Harrison's Principles of Internal Medicine, 22nd ed.
- Goodman & Gilman's Pharmacological Basis of Therapeutics
- FIGO Best Practice Guidance on Medical Treatment of Fibroids, 2025 (PMID 40927887)
- NASPAG Consensus on Tranexamic Acid, 2025
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