Pre-exposure prophylaxis (PrEP) is a strategy with significant historical precedent in the infectious disease field. Applied to HIV prevention, at-risk individuals would take PrEP to protect against HIV acquisition in case of any planned or unplanned exposure, potentially permitting HIV prophylactic control by the uninfected individual.
“All in this room are acutely aware of the scope of the HIV pandemic, with an unacceptable pace of 6,000 new daily HIV infections. These infections continue despite the availability of a robust portfolio of prevention tools, many of which when used in combination lead to prophylactic synergies,” said Raphael J. Landovitz, associate professor in the Division of Infectious Diseases, UCLA, Los Angeles, CA, at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, WA.
Landovitz shared updates on the current state of pre-exposure prophylaxis (PrEP) for HIV prevention and the need to mobilize clinical efforts, service delivery, education, implementation research, and policy to optimize PrEP access and use.
PrEP is a strategy with significant historical precedent in the infectious disease field. Applied to HIV prevention, at-risk individuals would take PrEP in advance of exposure to the virus to protect against any HIV acquisition in case of any planned or unplanned exposure, potentially permitting HIV prophylactic control by the uninfected individual.
Currently the only agent appropriate for PrEP is the combination of tenofovir disoproxil fumarate (TDF) and emtricitabine, a daily dose tablet with a relatively high barrier to resistance.
It was suggested that the ultimate minimalization of exposure to dose time could be achieved by having medication present by the time the exposure occurs in relevant tissues — ultimately culminating in 5 phase III randomized trials of oral PrEP to evaluate effectiveness.
The first study, the IPrEP study demonstrated a 42% reduction in incident HIV infections among individuals administered a daily oral regimen of TDF FTC. Results from a second study indicated a 6% effectiveness. The next CDC sponsored TDF2 trial, despite retention issue showed a significant result of 62% protection overall. The fourth PrEP study provided insight to the effectiveness of both arms in men and women. However the final VOICE trial was unable to provide confirmation of efficacy in women in any active arms.
Based on results from 3 of the studies, the FDA approved TDF FTC for prevention in at-risk men and women in 2012. However, although PrEP was shown to be highly effective, questions always persisted regarding the slow pace of adoption.
According to Landovitz, PrEP raised a few unique concerns: that PrEP will lead to decreased condom use and an increased number of sexual partners, sexually transmitted infections, and HIV infections including hepatitis C.
Researchers estimated that 99.9% reduction is achieved after approximately 5 daily doses of TDF FTC and a greater than 90% risk reduction persists after 7 days, but it is important to note that after those 7 days, protection appears to drop off.
Landovitz noted that support for adherences is a highly important component for PrEP services.
A number of investigation techniques are currently being applied to PrEP to evaluate their utility. These include interventions like customized text messaging, the iTab platform, and the “wise pill” electronic pill case for real time monitoring of dose taking — providing the opportunity to “intervene in the absence of dosing.”
Reports have highlighted that cost effectiveness is optimized when PrEP is targeted to patients who are at highest risk (including those who report non-condom-protected receptive anal intercourse, STIs in the past 6 months, or cocaine use in the past month).
There is quite a bit of activity underway to create infrastructure to deliver PrEP. Local jurisdictions are creating provider lists; consumers and providers are using the Internet to crowd source provider referrals, trouble shoot operational impasses, and share novel science; CBOs have developed informational materials for consumers on PrEP use and monitoring; the CDC and WHO have issued formal clinical guidance for providers; NYC has developed academic detailing methods and has already detailed 900 clinical practices to educate providers and has developed implementation seminars to teach clinics operational details of providing PrEP services.
What does the future hold? Just as the HIV treatment field did not cease following ART drug development, following the approval of ACT, Landovitz reminded that the PrEP field is really in its infancy. The optimization of PrEP use includes ongoing evaluation of novel drugs such as Maraviroc (as part of the HPTN 069/ACTG A5305 trial currently completing phase 2 safety evaluation). Long-acting therapies like rilpivirine, cabotegravir, and immunotherapies are involved as well.
Landovitz concluded, “I’d like to end this talk by reminding us that we should not be on the wrong side of history by allowing anyone to shame those seeking to protect their sexual health by using PrEP. Placing control in the hands of the HIV unaffected individual is a critical advance whose power cannot be underestimated. At least twice in modern US history, we have found ourselves on the wrong side of this argument. Let us go out and research, advocate, and minister to those seeking to nobly protect their sexual health by using PrEP.”