July 2017 – Pre-exposure Prophylaxis (PrEP) For HIV Infection

In September 2015, the World Health Organization (WHO) recommended that oral PrEP be offered as an additional prevention choice for persons who are at substantial risk for HIV infection. WHO reiterated that PrEP is an additional tool for HIV prevention and was not meant to replace the other well established HIV prevention interventions.

In high risk populations, numerous studies have demonstrated the effectiveness of daily PrEP in reducing the risk of acquiring HIV infection. Compliance with daily medication (adherence) is directly related to the success of PrEP. In these trials, those who acquired HIV infection whilst on PrEP almost always did not have detectable drug levels in their blood suggesting that they were not compliant with taking the medication used for PrEP.

Many health authorities have acknowledged PrEP’s potential in reducing new HIV infections. However, the challenge is in its implementation and there is limited experience in providing PrEP outside of the research setting. In Singapore, at least one restructured hospital has formally started a clinic with an infectious disease physician in attendance that provides PrEP to seronegative individuals at high risk for HIV infection. It is important to state that PrEP is more than just supplying the medications used for PrEP. A proper programme will need to be set up with behavioural counselling on sexual risk reduction, regular HIV testing, screening for other sexually transmitted infections (STI), ensuring adherence support and linking to treatment for those who acquire HIV infection whilst on PrEP. Studies have demonstrated the importance of peer counselling in the success of PrEP programme. The issue of “risk compensation” is important to highlight. The incidence of non HIV STIs has been found to be high in several PrEP studies. This issue of “increased” risk taking behaviour is debatable and a meta-analysis found no reduction in the reported use of condoms during sex in the study participants.

It is important to reiterate that PrEP is meant for a selected group of patients at substantial risk of acquiring HIV infection. WHO has identified the following as persons who may benefit from PrEP:

  1. HIV negative individual AND
  2. A seropositive partner who is not virally controlled OR
  3. Sexually active in a high HIV incidence/prevalence population AND any one of the following:
  1. Vaginal or anal sexual intercourse without condom
  2. A sexual partner with one or more HIV risk factors
  3. A history of sexually transmitted infection (STI) by laboratory testing or self report or syndromic STI treatment OR
  4. Use of Postexposure prophylaxis OR
  5. Requesting for PrEP

PrEP should not be used for:

  1. HIV positive individuals or persons who have unknown HIV status
  2. Presence of renal impairment with creatinine clearance of <60ml/min
  3. Signs and symptoms of acute HIV infection
  4. Allergy to one or more of the drugs used in PrEP

PrEP is not meant to be taken indefinitely. Once the risk factors have been removed, then PrEP should be discontinued. For example, this may occur in serodiscordant couples for whom the HIV positive partner is fully compliant with treatment, achieved control of HIV infection and is monogamous.

There has been interest in the use of “on demand or event driven” PrEP. In this form of PrEP, instead of taking PrEP medication daily, the iPERGAY study has reported that PrEP may be taken for a short period starting 2-24 hours before the sex act and taking daily treatment until after the last sex act. The “on demand” PrEP has to be re-started for the next episode of sexual activity. Some patients may prefer this approach and the IPERGAY trial has reported that there was a 97% reduction in HIV incidence. The patient population in the iPERGAY trial were men who have sex with men (MSM) and transgender women.

Are there gender differences in PrEP? The studies of daily PrEP in women have not demonstrated similar effectiveness in reducing the risk of HIV infection. In the Partners PrEP trial carried out in serodiscordant couples in Kenya and Uganda, risk reduction of HIV transmission using Truvada was 84% in men and 66% in women. The reasons for this difference are being further investigated. Early data showed that there may be different drug bioavailability in rectal and vaginal tissues. At this time, there is insufficient data to recommend the use of “on demand” PrEP for women.

What about the future of PrEP? There are numerous studies investigating the use of agents other than tenofovir based regimens for PrEP. These include the use of long acting injectables and other topical formulations. The scientific data is now available for the safe use of PrEP in the prevention of HIV infection in those individuals at high risk of acquiring the infection. The next challenge is in the effective implementation of PrEP in the overall strategy of HIV prevention.