HIV preexposure prophylaxis (PrEP) is an effective HIV prevention modality whose implementation continues to increase among those at high risk of infection.1,2 Current guidelines suggest considering PrEP for men who have sex with men having frequent condomless sex, people who share injection drug use paraphernalia, and those with heterosexual exposures with greater risk of HIV acquisition.3,4 PrEP usually refers to daily use of tenofovir disoproxil fumarate with emtricitabine (TDF/FTC), but on-demand PrEP is another proven method of PrEP administration for men who have sex with men designed to reduce pill burden by using TDF/FTC just before and shortly after condomless sex.5 This is in contrast to HIV postexposure prophylaxis (PEP), which refers to the use of a 28-day course of antiretroviral (ARV) medications as soon as possible and no more than 72 hours after a potential exposure to HIV to prevent infection.
In our clinical practice, we have identified a cohort of individuals who do not meet criteria for daily or on-demand PrEP, given their relative infrequency of potential HIV exposures, but who nevertheless remain at risk and are eager to use a biomedical HIV prevention strategy. We initiated these patients on on-demand PEP, which we refer to as HIV postexposure prophylaxis-in-Pocket (or “PIP”), as a strategy to prevent HIV while mitigating the potential drawbacks of conventional PEP [eg, emergency department (ED) evaluation, patient attrition], on-demand PrEP (unclear evidence for efficacy with very infrequent HIV exposures), and daily PrEP (requirement for daily pill-taking, side effects). We discuss the demographics, risk factors, and outcomes of our patients using this HIV prevention modality.
We performed a retrospective analysis of patients who were referred to either the University Health Network HIV Prevention Clinic (Toronto General Hospital site) or St. Michael's Hospital HIV Clinic, both in Toronto, Canada, between January 1, 2013, and September 30, 2017, inclusive. The patients were referred from family practitioners, EDs, or sexual health clinics for consideration of HIV PEP or PrEP, but ultimately initiated on PIP. We extracted data based on a standardized tool that included demographic data, duration on PIP, instances of PIP use, adherence to PIP, and changes between HIV prevention modalities. Data were entered into a Microsoft Excel database (Redmond, WA) and descriptive statistics were performed.
PIP in Clinical Practice
After consultation in HIV prevention clinics, patients deemed less suitable for daily or on-demand PrEP3–5 but still reporting potential for HIV exposure were offered PIP. Patients initiated on PIP were followed at regular 3–6-month intervals with repeat routine blood work, (complete blood count, electrolytes, creatinine, liver enzyme testing, and bilirubin) in addition to HIV and sexually transmitted infection testing at each visit as deemed clinically appropriate, along with safer sexual counseling. Sexually transmitted infection testing involved urine polymerase chain reaction for chlamydia and gonorrhea, rectal and pharyngeal swabs for chlamydia and gonorrhea culture, and serum for syphilis screening. PIP initiation and treatment protocols adhered to current PEP guidelines.4,6 Patients were educated to initiate PIP immediately (and not later than 72 hours) after a perceived high-risk HIV exposure. TDF/FTC plus dolutegravir was prescribed. Patients were counseled to fill the prescription and have it readily available in case an exposure occurred. Patients who initiated PIP before their next scheduled visit were instructed to come to clinic as soon as possible and not longer than a week after initiating the medication for clinical evaluation and baseline investigations, to confirm whether a full 28-day course should be taken.4,6 Those who used their PIP were provided with another prescription for 28 days of ARVs for potential future exposures. Patients were regularly reminded of the ability to transition between PIP and PrEP based on the frequency and perceived risk of condomless sexual practices.
Thirty patients prescribed PIP were identified between January 2013 and September 2017. A description of the demographics and PIP use can be viewed in Table 1. Twenty-nine (96.7%) were men who have sex with men, whereas one heterosexual woman in a serodiscordant relationship was included. The mean age was 38 years (range 27–60). Participants contributed a total of 262 patient-months (21.8 patient-years) of follow-up. All the patients were initially referred for PrEP.
Of the 30 who were initiated on PIP, 4 (13.3%) patients were initially on PrEP but transitioned to PIP due to very infrequent sexual risk activity (eg, MSM with >95% condom use), whereas another 4 (13.3%) patients transitioned to daily PrEP based on follow-up evaluation of sexual practices and HIV risk.
Four (13.3%) patients actually used their PIP medications, and all 4 were able to immediately take their ARVs within less than 10 hours of a higher-risk sexual exposure. These 4 patients each only used one 28-day course of PIP, and were adherent to their medications by self-report. The specific exposures included 2 episodes of receptive anal sex where a condom broke (one with a known HIV-positive partner and one with an unknown-status partner), an episode of condomless anal receptive sex, and an episode of condomless anal insertive sex, both with individuals of unknown HIV serostatus. All who started ARVs for PIP were able to be seen in clinic within a week for clinical evaluation and blood work. There were no HIV seroconversions in anyone prescribed PIP, whether they used ARVs or not, over the course of this study.
HIV PIP may be a pragmatic and effective HIV prevention modality for individuals who are interested in biomedical strategies, but not candidates for daily or on-demand PrEP based on current data. Here, we demonstrate no new HIV seroconversions in a cohort of 30 individuals on PIP for a combined duration of 21.8 patient-years.
Although on-demand PrEP may seem to be an attractive option for MSM with lower frequency exposures, the population described here still has far fewer potential HIV exposures than described in the ANRS IPERGAY study5,7 and the efficacy of on-demand PrEP with such infrequent exposures has not been evaluated. Importantly, even in a recently reported substudy of the trial, which observed no HIV seroconversions during the 134 person-years of follow-up where participants were adherent to on-demand PrEP and reported less frequent condomless sexual encounters than the main study cohort, participants still reported a median of 5 exposures per month.7 In contrast to daily and on-demand PrEP, HIV PEP is a retroactive HIV prevention modality that involves initiating a 28-day course of a 3-drug antiretroviral therapy (ART) regimen within 72 hours of a potential HIV exposure, and significantly reduces the potential for HIV seroconversions.8,9 PEP is primarily used for HIV prevention in those with one-time or very low-frequency HIV exposures. Patients seeking PEP care typically present to EDs for ART initiation and are then referred for follow-up care in specialized clinics. Unfortunately, there is significant attrition between the ED and clinic, and poor adherence to the 28-day ART regimen and subsequent follow-up.10,11
We believe that PIP offers several important benefits over other HIV prevention modalities for a carefully selected population with low-frequency HIV exposures, but those who still may be at greater risk of HIV acquisition compared with the general public. These include: (1) immediate access to treatment should an exposure occur without the urgent requirement to present to clinic or, more commonly, an ED, for initiation of therapy, (2) avoidance of the potential associated side effects of a daily PrEP regimen, (3) decreased costs compared with daily PrEP, and (4) a high level of self-empowerment to guide their own medical management.
For PIP to be successful, the patient must be well educated regarding the importance of avoiding exposures, for example through regular condom use during sex. Given that patients are instructed to initiate PIP as soon as possible after a potential HIV exposure and to present to their physician within 1 week for assessment, we acknowledge that PIP will work best with patients who exhibit excellent health literacy, insight, and reliability. In this study, there were no issues with patient follow-up or side effects of PIP; however, we recognize that patients were carefully chosen as PIP candidates.
Interestingly, within this cohort of 30 patients, 8 (26.7%) transitioned from one HIV prevention modality to another; this fluidity between HIV prevention modalities has previously been described in those transitioning from PEP to PrEP.12 As the behaviors and preferences of an individual evolve, clinicians should continuously evaluate the mode of HIV prevention at each clinical appointment and adjust to best suit their patient's needs.
Limitations of this work include the retrospective design, which precluded our ability to collect more detailed information about participants' HIV risk behaviors, the predominance of MSM within the study cohort, which limits our ability to comment on the suitability of PIP for other populations, and the modest sample size. Future studies should evaluate PIP use and efficacy in a prospective manner.
We believe that PIP is a useful strategy for HIV prevention in patients who have infrequent potential HIV exposures and are not candidates for HIV PrEP. Our data demonstrate the fluidity with which patients can transition between HIV prevention modalities to best suit their needs, and expand the range of options available to those at risk of infection.
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