September 2019

Leo Moore, MD, MSHPM

HIV pre-exposure prophylaxis, or PrEP, is the use of antiretroviral medication to prevent acquisition of HIV infection. The current gold standard for PrEP is daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC or Truvada™), which can be used by adults and adolescents of all genders and sexual orientations to prevent HIV acquisition from injection drug use and sexual exposure. In addition, there are now two important developments in PrEP for subsets of patients.

This article will summarize on-demand or PrEP 2-1-1, a new off-label dosing regimen for men who have sex with men (MSM) with infrequent sexual exposures. In addition, there will be a brief update on tenofovir alafenamide/emtricitabine (TAF/FTC or Descovy™), which was recently recommended for FDA approval as daily PrEP for MSM and transgender women who have sex with men.

Clinicians are encouraged to read our updated CME article, HIV Prevention with PrEP, which now includes on-demand PrEP and other emerging therapeutic modalities.

On-Demand HIV PrEP/2-1-1

On-demand PrEP, also referred to as 2-1-1, peri-coital PrEP, intermittent PrEP, and event driven PrEP, is an off-label, intermittent dosing schedule using TDF/FTC. While daily use of PrEP is optimal, on-demand PrEP is effective for HIV prevention among MSM and is an alternative to daily PrEP for MSM with infrequent sexual exposures. This 2-1-1 dosing for MSM is supported by the International Antiviral Society-USA Panel (IAS-USA) and is endorsed by Los Angeles County Department of Public Health (LAC DPH) for MSM who can articulate a clear understanding of correct usage and would otherwise not adhere to daily PrEP.

2-1-1 Dosing

The patient takes a total of 4 pills of TDF/FTC (containing 300 mg of TDF and 200 mg of FTC) using the following 2-1-1-schedule:

• 2 pills, 2-24 hours before sex (with food)
• 1 pill, 24 hours after the first dose
• 1 pill, 24 hours later

If the patient continues to have sex for consecutive days, they must continue taking 1 tablet of TDF/FTC per day until 48 hours has passed since their last sexual encounter.

2-1-1 Efficacy Data

On-demand PrEP efficacy data comes from two studies of alternative TDF/FTC dosing for MSM.^1,2 Ipergay, a randomized placebo controlled clinical trial, showed that taking TDF/FTC on a 2-1-1 schedule reduced risk of HIV infection by 86% in MSM compared to placebo. Interim data from an open-label study, Prévenir, presented in August 2018, showed that PrEP 2-1-1 was as effective as daily PrEP with zero new infections among 1,629 participants who used the 2-1-1 and/or daily PrEP method correctly for a mean of 7 months.

Per IAS-USA, the 2-1-1 regimen achieved target exposures of tenofovir diphosphate and emtricitabine triphosphate in colorectal tissue at the time of coitus in 81% and 98% of the population when administered 2 and 24 hours before coitus, respectively. Based on this, IAS-USA recommends that the first (double) dose of TDF/FTC should ideally be taken closer to the 24-hour pre-coital time than the 2-hour time.

On-demand dosing has only been studied in MSM and a small number of transgender and cisgender heterosexual people. Based on current study data, on-demand dosing appears to be effective for anal sex only. Vaginal and cervical tissue require more time and dose exposure to TDF/FTC to reach protective levels than the 2-1-1 method allows. For example, vaginal tissue requires 20 daily doses of PrEP to reach maximal protective levels.³

For a summary of trials of on-demand PrEP, review the San Francisco AIDS Foundation’s “For people having anal sex, PrEP 2-1-1 is effective at preventing HIV” blog.

Patients Who Might Benefit from 2-1-1 Dosing

Based on current efficacy data, 2-1-1 is only recommended for anal sex. PrEP 2-1-1 may be suitable for MSM who experience periods of sexual inactivity, MSM who inconsistently or never use condoms during sex, or MSM who otherwise do not want to commit to continuous daily PrEP therapy.

PrEP 211 is not recommended for people having vaginal sex or using their front hole (neo-vagina) for sex. The 2-1-1 regimen also is not recommended for patients with active hepatitis B infection, because of risks of reactivation and hepatitis B viral resistance.

LAC DPH endorses a shared decision-making approach, where clinicians discuss with MSM the very high effectiveness of PrEP using either initiation strategy and help patients decide what is going to be most effective for them.

Counseling

MSM should be advised that daily PrEP is the best method for preventing HIV but that 2-1-1 is an effective alternative for infrequent sexual exposures. As is the case for daily PrEP, strict adherence to 2-1-1 dosing is critical for maximum efficacy. MSM considering on-demand PrEP should be counseled about the importance of following the 2-1-1 schedule and should be able to articulate a clear understanding of correct usage. Patients using the 2-1-1 schedule should be advised that taking the first dose 24 hours before sex provides the best protection but that taking the first dose as little as 2 hours before sex also reduces HIV risk.

All patients using PrEP (daily or on-demand) should be encouraged to see a clinician every 3 months to monitor for side effects and to test for new HIV infections or other sexually transmitted infections (STIs). In addition, patients should be counseled on risk-reduction strategies including the importance of consistent condom use to prevent STIs and serve as a second layer of protection against HIV acquisition.

Brief Update on Tenofovir Alafenamide/Emtricitabine (Descovy™)

On August 7, 2019, an FDA advisory panel voted in favor of approving tenofovir alafenamide/emtricitabine (TAF/FTC or Descovy) for daily use PrEP in MSM and transgender women who have sex with men. TAF/FTC is already FDA approved to treat chronic HIV. Due to the lack of trial data for cisgender women and transgender men, the FDA advisory panel did not recommend approval of TAF/FTC in these priority groups. If the FDA ultimately approves TAF/FTC for PrEP, there will be two daily PrEP options for MSM and transgender women who have sex with men.

HIV Prevention with PrEP

PrEP is an important HIV prevention tool that every primary care provider should have in their toolbox. When taken as prescribed, PrEP reduces the risk of HIV acquisition up to 99%.⁴

Primary care providers are encouraged to read the updated Rx for Prevention article, HIV Prevention with PrEP, for more detailed information about how and when to prescribe PrEP. This CME article reviews how to take a sexual history to identify patients at high risk of acquiring HIV and follows with frequently asked questions (FAQs) designed to provide primary care providers with the knowledge and confidence to prescribe PrEP to their high-risk patients. It also includes resources to help provide PrEP to low income residents in Los Angeles County. Interested clinicians can also watch the on-demand CME webinar, HIV Prevention with PrEP.

References

1. Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 Infection. N Engl J Med. 2015;373(23):2237-2246. doi:10.1056/NEJMoa1506273.
2. Final results from the ANRS Prévenir study [press release]. Paris, France: Assistance Hopitaux Publique de Paris; July 24, 2018. http://www.anrs.fr/sites/default/files/2018-07/PR%20Prevenir_web.pdf. Accessed August 30, 2019.
3. World Health Organization. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: 2016 Recommendations for a Public Health Approach, Second Edition. Geneva, Switzerland: World Health Organization; 2016. https://apps.who.int/iris/bitstream/handle/10665/208825/9789241549684_eng.pdf;jsessionid=BAE108B9664F51B7F5847EB76BBDDBBF?sequence=1. Accessed August 30, 2019.
4. Supervie V, Barrett M, Kahn JS, et al. Modeling dynamic interactions between pre-exposure prophylaxis interventions & treatment programs: predicting HIV transmission & resistance. Sci Rep. 2011;1:185. doi:10.1038/srep00185.