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PrEP for HIV Prevention: Mechanism, Effectiveness & Clinical Guidance

What Is PrEP?

Pre‑Exposure Prophylaxis (PrEP) is daily oral antiretroviral medication taken by HIV‑negative individuals at substantial risk to prevent acquisition of HIV.

Approved Regimens (US)

RegimenComponentsIndicationDosing
Truvada®TDF 300 mg + FTC 200 mgAll at‑risk adults/adolescents ≥35 kgDaily
Descovy®TAF 25 mg + FTC 200 mgCis‑gender MSM & transgender women (not studied in receptive vaginal sex)Daily
Apretude® (CAB‑LA)Cabotegravir 600 mg IMAll at‑risk adults/adolescents ≥35 kgLoading: 2 doses 1 mo apart; then q2mo

Mechanism of Action

  1. Pre‑exposure: Drug concentrates in mucosal tissues (rectal, vaginal, penile).
  2. Viral Entry: HIV binds CD4/CCR5/CXCR4.
  3. Reverse Transcription Block: TDF/FTC (NRTIs) compete with natural nucleotides → chain termination. Cabotegravir (INSTI) blocks integration.
  4. No Establishment of Infection: Without reverse transcription/integration, provirus cannot form.

Effectiveness

  • Daily oral PrEP: 99% risk reduction with adherence (≥4 doses/week for rectal, daily for vaginal).
  • Event‑driven (2‑1‑1) dosing: Effective for MSM (IPERGAY, PREVENIR).
  • Cabotegravir LA: Superior to daily TDF/FTC in HPTN 083/084 (66–89% relative reduction).

Key Clinical Steps

  1. Risk Assessment: Sexual/injection practices, partner status, STI history.
  2. Baseline Labs: HIV Ag/Ab (4th gen) negative, renal function (eGFR ≥60 for TDF, ≥30 for TAF), HBV status, STI screen.
  3. Counseling: Adherence, condom use for STI prevention, follow‑up schedule.
  4. Prescribe & Monitor: q3mo HIV test, renal function q6mo (TDF), STI screen, adherence support.

Special Populations

  • Pregnancy/Breastfeeding: TDF/FTC safe; cabotegravir data limited.
  • Adolescents: Approved ≥35 kg; adherence support critical.
  • Transgender Persons: Data supports TDF/FTC & cabotegravir; Descovy not studied for receptive vaginal sex.
  • Renal Impairment: Prefer TAF or cabotegravir.

Access & Cost

  • Most insurers cover (ACA preventive service).
  • Gilead Advancing Access / ViiV Connect patient assistance.
  • Generic TDF/FTC available (lower cost).

PrEP ≠ PEP

Post‑Exposure Prophylaxis (PEP) = 28‑day emergency course started ≤72h after exposure. Different indication, regimen, urgency.

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