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PrEP talk: An update on HIV pre-exposure prophylaxis

Background

Behavioral interventions have been effective at lowering HIV transmission rates in British Columbia. Along with treatment as prevention, they remain the cornerstone of HIV prevention. However, infection rates have plateaued for the last 5 years and new interventions are needed to reach those individuals not captured by current prevention strategies.

Pre-exposure prophylaxis (PrEP) is one approach that is showing promise.

Evidence

The effectiveness of daily PrEP in men who have sex with men (MSM) was first demonstrated in the iPrEx trial in 2010.[1]  Research now supports expanding use to injection drug users, serodiscordant heterosexual couples, and transgender men and women at risk.  

Kaiser Permanente has evaluated PrEP use from 2012 onwards.[2]  Despite very high rates of risky sexual behavior in their cohort of over 600 men, not a single new HIV infection has occurred. 

Similar results were found in the PROUD study, which assessed PrEP uptake in a group of high risk MSM in the UK.[3]  HIV negative participants were randomized to immediately receive PrEP or wait a year before initiating PrEP. This study was terminated early because of the high number of infections in the delayed PrEP group. There were three new infections in the immediate PrEP group; however, closer inspection of these infections revealed one person was HIV positive before the trial and the other two had stopped taking their PrEP.

In every clinical trial of PrEP so far, there have been zero cases of HIV infection in someone properly taking their medication.

Access

Despite the evidence, widespread adoption of PrEP in Canada and globally has been slow. The main barrier to obtaining PrEP is the cost (~$1000), as most provincial and private insurance programs do not cover it**. Indeed, those at highest risk of HIV are the least able to afford it. 

In response, a community-led initiative has emerged where generic PrEP is purchased online at a substantially reduced price. Understandably, there are quality and safety concerns, although several recent studies have provided some degree of confidence, demonstrating that samples bought online contained active medicine and met internationally recognized standards.[4,5]

Improving access through dosage?

To minimize cost and toxicity of PrEP, some suggest that it be taken intermittently or only during times of high-risk activity. The iPrEx and PROUD studies suggest that 4 tablets per week may be sufficient to maintain protective drug levels. 

The Ipergay study tested a novel strategy for intermittent PrEP use that appeared to be effective (there were zero infections in those who were adherent to medication).[6]  While there was some concern about the validity of this study initially, subsequent analysis now supports use of event-driven PrEP in certain circumstances.

Considerations and risks

Toxicity to PrEP is rare and generally limited to gastrointestinal side effects. However, it has been associated with kidney toxicity and so baseline renal function must be established and monitored every three months. 

It is essential to ensure your patient is HIV negative, ideally with a 4th generation HIV antigen/antibody test, before starting PrEP. Antiretroviral resistance can occur rapidly and complicate proper HIV therapy if PrEP is used in an individual with established HIV infection. 

It is also important to rule out chronic Hepatitis B infection in anyone initiating PrEP. Tenofovir and FTC have excellent activity against Hepatitis B and there is a risk of Hepatitis B flare if a PrEP user decides to discontinue PrEP.

Aside from drug toxicity, two other major risks of PrEP exist:

  1. Risk compensation: There is a possibility that widespread use of PrEP in a community already at high risk for STI might fuel further increases in STI incidence. Analyses of current data have not shown consistent evidence that this occurs; in fact, there may be the opposite effect.  When PrEP is provided as part of a structured STI prevention program, mathematical models indicate that STI rates may actually decline as more infections are detected and treated. 
  2. PrEP failure: There have been three described cases of HIV infection occurring in an individual who is taking PrEP correctly. The first two failures occurred as a result of exposure to HIV that was medication-resistant. The third was a new infection with wild-type or non-resistant HIV.  These cases act as a reminder that PrEP must always be provided together with a comprehensive preventive package and that PrEP should never be used as a substitute for safer sex.

Conclusions

The risk of PrEP failure should not discourage us from offering this prevention strategy to high-risk men and women. Anyone who has had a recent rectal STI or indicates they engage in unprotected anal intercourse should be counseled on PrEP. There is also a simple, validated screening tool called the HIRI-MSM that can be used to identify MSM at high risk of HIV infection.[7] 

In the era of PrEP, even a single new case of HIV is unacceptable. As health care providers, we should be prepared to recognize those at high risk and provide accurate information on the risks and benefits of this new intervention.

**NOTE: As of January 1, 2018, generic PrEP is available free-of-charge in British Columbia to individuals at high risk of HIV infection. This includes men and transwomen who have sex with men, people who use injection drugs, and people who have sex with individuals living with HIV.

References

  1. Grant RM et al. Pre-exposure chemoprophylaxis for HIV prevention in men who have sex with men. New England Journal of Medicine 2010; 363:2587-2599. Full text article.
  2. Marcus JL et al. Pre-exposure prophylaxis for HIV prevention in a large integrated health care system: Adherence, renal safety and discontinuation. JAIDS 2016; 73(5):540-546.
  3. McCormack S et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectivenss results from the pilot phase of a pragmatic open-label randomized trial. Lancet 2016; 387(10013): 53-60. Full text article.
  4. Aloysius I, Savage A, Zdravkov J, Korologou-Lenden R, Hill A, Smith R, Houghton-Price V, Boffito M, Nwokolo N. InterPrEP. Internet-based pre-exposure prophylaxis with generic tenofovir DF/emtricitabine in London: An analysis of outcomes in 641 patients. Journal of Virus Eradication 2017; 3. Full text article.
  5. Lott AC, Naccarato M, Turton R. POPPEE: Purchasing online pre-exposure prophylaxis (PrEP) pills to evaluate equivalence. Oral presentation. Canadian Association for HIV Research (CAHR) conference, April 6-9 2017, Montreal, Quebec, Canada.
  6. Antoni G et al. On-demand PrEP with TDF/FTC remains highly effective among MSM with infrequent sexual intercourse: A sub-study of the ANRS IPERGAY trial. Oral presentation. International AIDS Society (IAS) conference, 23-26 July 2017, Paris, France.
  7. Wilton J, Kain T, Fowler S, Hart T, Grennan T, Maxwell J, Tan D. Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: Disconnect between objective and subjective HIV risk. Journal of the International AIDS Society 2016; 19(1): 20777. Full text article.

Categories: Current practice

Search related content: HIV, PrEP, prevention, pre-exposure prophylaxis, research

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