Pre-exposure Prophylaxis (PrEP)

 Principles & Procedure

1

PrEP should be used in adults at high-risk of acquiring HIV infection when condoms are not used consistently. Before PrEP is initiated, HBV serology status should be documented

  • Recommended in HIV-negative men who have sex with men (MSM) and transgender individuals when condoms are not used consistently with casual partners or with partners with HIV who are not virally suppressed on treatment. A recent STI, use of post-exposure prophylaxis or chem-sex may be markers of increased risk for HIV
  • May be considered in HIV-negative heterosexual women and men who are inconsistent in their use of condoms and have multiple sexual partners where some may have untreated or inadequately suppressed HIV infection

2

PrEP is a medical intervention that provides a high level of protection against HIV acquisition but does not protect against other STIs or pregnancy and should be used in combination with other preventive interventions. PrEP should be supervised by a doctor, experienced with sexual health and use of HIV medicines, possibly as part of a shared care arrangement

Recommended Procedures

  • Documented negative fourth generation HIV test a week prior to starting PrEP. In case of suspicion of acute HIV-infection, an RNA test on plasma should also be performed, see Primary HIV Infection (PHI). During PrEP, a fourth generation HIV test should be repeated at one month and then every 3 months. In stable long-term users who are on 6 monthly prescriptions an interim fourth generation test that can be performed without a visit to clinic
  • PrEP should be changed to triple-drug ART without interruption in case of early clinical signs of HIV seroconversion or a positive HIV diagnostic test which may necessitate referral for evaluation to an HIV unit, see ART initiation 
  • PrEP may continue during pregnancy and breastfeeding if the risk of acquiring HIV persists
  • Before PrEP is initiated, HBV serology status should be documented. If HBsAg positive, see Clinical Management and Treatment of HBV and HCV Co-infection. 
  • Counsel that PrEP does not prevent other types of STIs; screen for STI (syphilis, chlamydia, gonorrhoeae, HAV, HCV) when starting PrEP and regularly during use of PrEP, see Assessment of Initial & Subsequent Visits. All persons under PrEP should be offered vaccinations against HAV, HBV, HPV and monkeypox virus. Doxycycline post exposure prophylaxis, 200 mg within 24 to 72h after sexual intercourse, proved to be effective in preventing bacterial STIs in MSM with the caveat of the unknown long terms effects on microbiota and STIs resistance. It can be proposed to persons with repeated STIs on a case by case basis.
  • Counsel that TDF-based PrEP may rarely impact renal and bone health, see Bone Disease: Screening and Diagnosis, Approach to Fracture Reduction, Kidney Disease: Definition, Diagnosis and Management, ARV-associated Nephrotoxicity. Check renal function within the first 3 months of starting PrEP and check renal function and bone health during PrEP according to guidelines on TDF use
  • Counsel that PrEP, like other prevention methods, only works when it is taken. An adherence check one month after starting is recommended, and counselling may be required in follow-up
  • Counsel that PrEP can be prescribed long-term but that each consecutive PrEP prescription should cover the period to the next visit which will be every 3 months for the majority but could be a maximum of 6 months in stable long-term users (over one year of daily PrEP)

3

PrEP regimen

  • The most common drug available is a generic version with 300mg of tenofovir (formulated as disoproxil fumarate/maleate/phosphate) combined with 200mg of emtricitabine (TDF/FTC). In certain countries, TDF is labelled as 245 mg rather than 300 mg to reflect the amount of the prodrug (tenofovir disoproxil) rather than the fumarate salt (tenofovir disoproxil fumarate)
  • The effectiveness of daily and on-demand regimens of TDF/FTC has been extensively evaluated in clinical studies in men, but on demand has only been evaluated in pharmacokinetic/pharmacodynamic (PK/ PD) studies for the female genital tract (FGT) and not at all for neovaginal/ neopenile tissues
  • TAF/FTC could be considered, if available, when creatinine clearance or bone mineral density preclude TDF/FTC. TAF/FTC has been evaluated as a daily regimen in comparison to TDF/FTC in men and transgender women. It was non-inferior, with a statistically significant benefit for renal and bone biomarkers
  • Long-acting cabotegravir is available on application to compassionate release program, pending EMA approval, for individuals for whom TDF/FTC is contraindicated

  • TDF/FTC 300*/200 mg 1 tablet qd. In both men and women PrEP should be taken for 7 days before the first exposure and stopped 7 days after the last exposure
  • For men only, PrEP may be dosed ‘on demand’ (double dose of TDF/ FTC 2-24 hours before each sexual intercourse, followed by two single doses of TDF/FTC, 24 and 48 hours after the first drug intake; no data for TAF/FTC so far). There are no efficacy data with on demand PrEP with TDF/FTC in women
  • PK/PD studies comparing TAF/FTC to TDF/FTC suggest that the recommandations for starting and stopping TAF/FTC can be extrapolated from TDF/FTC
  • Use of generic formulations of TDF/FTC, if and where available, may help to improve the cost-effectiveness of PrEP, which is essential for its use as public health approach
  • Rates of adverse eGFR declines are generally low for those using TDF for PrEP, but PrEP users with the highest risk of adverse renal outcomes on TDF and most in need for systematic monitoring of renal function are older individuals and those with pre-existing renal impairment. Data on renal outcomes with use of TDF vs. TAF in those on PrEP with renal impairment is limited, recommendations to follow guidelines on TDF use in persons with HIV, see Kidney Disease: Definition, Diagnosis and Management, ARV-associated Nephrotoxicity, Indications and Tests for Proximal Renal Tubulopathy (PRT). Similarly, no data on use of “on demand” vs daily PrEP for renal outcomes
  • Any person presenting with low PrEP adherence and a condomless at risk sexual intercourse should benefit from post exposure prophylaxis. Low adherence is defined:
    •  For men and women on daily regimen: less than 4 pills a week, regardless of the distribution
    •  For men on on demand regimen: less than 1 pill before and 1 pill after sexual intercourse