Retention in event-driven PrEP among young Thai men who have sex with men at risk of HIV acquisition

Abstract

Background: Daily pre-exposure prophylaxis (PrEP) regimen of tenofovir/emtricitabine (TDF/FTC) tablet is the standard of care for HIV prevention in Thailand. Event-driven PrEP (ED-PrEP), taking two loading pills 2–24 h prior to sex and two doses afterward, is considered an alternative regimen. This pilot study aimed to describe accuracy of and retention in ED-PrEP use among Thai young men who have sex with men (YMSM).

Methods: A cohort of YMSM aged 15–19 years at risk of HIV infection, defined as reporting irregular condom use or having an HIV-positive sexual partner, was enrolled. All participants were provided oral TDF/FTC, condoms, and the “Raincoat” mobile application, which reminds users when to administer ED-PrEP. Participants attended clinic visits at Months 1, 3, and 6 and followed up by phone at Months 2, 4, and 5. Proper use of ED-PrEP was reported in person-months.

Results: From August 2020 to July 2021, 36 YMSM with a median age of 18.7 (IQR, 17.5–19.4) years were enrolled. Thirty-two participants (88.9%, 95% CI: 73.9–96.9%) were retained at 6 months. No HIV incidence occurred during this study period. Of 197 person-months of follow-up, 69 (35%) involved sexual activity. In this group, 61% used ED-PrEP correctly. “Unplanned sexual activity” was the most commonly cited reason for incorrect use.

Conclusions: YMSM who have infrequent sex had very high retention in ED-PrEP. However, about one-third of the sexually active period, ED-PrEP was not used correctly due to not taking the loading dose, suggesting that this regimen may not be suitable for unanticipated sexual activity.

Keywords

Young men who have sex with men event-driven pre-exposure prophylaxis retention accuracy adolescents

Background

In 2020, an estimated 4,800 new cases of HIV arose in Thailand,¹ and 38% of HIV incidence was among Thai men who have sex with men (MSM).^1,2 An alarming trend of HIV burden has emerged among young MSM (YMSM), who see a 12.1% rate of new HIV infections and earlier sexual engagement than their heterosexual peers.³ A study among YMSM aged 18–24 years in Bangkok reported a baseline HIV prevalence of 21.2% and incidence of 7.4 per 100 person-years between 2006 and 2014,⁴ which was higher than the overall rate among MSM (5.9 per 100 person-years) during the same period of time.⁵ In a seroprevalence study among 4,629 young Thai male conscripts at age 21 years old, overall HIV prevalence among MSM was 4.0% compared with 0.7% in non-MSM.⁶ A study at the Silom Community Clinic in Bangkok, Thailand, reported that the HIV incidence among young MSM 13–21 years is 10 per 100-person years which is 4.2 times higher than MSM >30 years of age.⁷ The rise in HIV burden among YMSM is not limited to Thailand. In Asia and the Pacific, 44% and 34% of new HIV infections in 2019 were among MSM and people aged 15–24 years, respectively.⁸

In 2011, the US Centers for Disease Control and Prevention (CDC) issued preliminary guidance for the use of oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as primary prophylaxis against HIV infection for MSM at high risk of exposure.⁹ The once-daily regimen was based on the iPrEx study, which demonstrated a 44% reduction of HIV incidence for TDF/FTC users, with minimal side effects.¹⁰ While the daily PrEP regimen is the standard of care for HIV prevention in Thailand, daily adherence remains a challenge. A study among Thai YMSM and young transgender women (YTGW) reported a 73% retention rate at 6 months but low adherence rates of 51% and 44% at months 3 and 6, respectively.⁷ Given the strict routine of daily oral PrEP, injectable and event-driven PrEP (ED-PrEP, also called intermittent, non-daily, on-demand PrEP or 2-1-1 PrEP) are alternative regimens.^8,13 In 2015, the IPERGAY trial evaluated the efficacy of ED-PrEP, which consists of a double dose of two co-formulated TDF/FTC pills taken between 2 to 24 h in advance of anticipated sex, then, one pill at 24 and 48 h.^1,9,10 Compared to placebo, ED-PrEP was associated with an 86% relative reduction in risk of HIV infection among MSM in the IPERGAY study^1,9,10 and 97% in the open-label extension phase (IPERGAY-OLE).¹¹ A study from France among more than 3,000 participants reported low HIV incidence as 0.11 cases per 100 person-years in both daily PrEP and on demand PrEP arms.¹²

In 2021, the US Clinical Practice Guidelines recommended “2-1-1” dosing as an alternative to daily dosing for MSM.⁸ The on-demand nature and “2-1-1” schedule (i.e. four pills per sexual activity) of ED-PrEP may make it preferable to the once-daily regimen, especially for those who have infrequent sex. However, the regimen requires proper use and planning for sex at least 2 h in advance, both of which are limitations to its effectiveness. Given that ED-PrEP is a relatively novel method of HIV prevention, particularly in Thailand, data on the accuracy of and retention in ED-PrEP use among Thai YMSM are sparse. This pilot study reports the accuracy of ED-PrEP use and program retention among Thai YMSM.

Methods

This prospective study in a cohort of YMSM aged 15–19 years was conducted at Adolescent HIV Treatment and Prevention Clinic, based in King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Ethical approval was provided by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, IRB No. 286/63. According to the Thai Public Health Ministerial Regulation (2019), Thai adolescents at least 15 years of age have autonomy to access sexual health services, including anti-HIV testing and PrEP.¹³

YMSM were enrolled if they reported at least one of the following within the past 6 months: (1) irregular condom use during anal intercourse, (2) had more than one sexual partner, or (3) had a sexual partner with HIV. At enrolment, participants were screened for anti-HIV antibodies and HBsAg. They were excluded if they had a documented positive result from an anti-HIV or HBsAg laboratory test, acute retroviral syndrome, TDF/FTC allergy, or contraindication.

Eligible YMSM were presented information about the ED-PrEP regimen. YMSM who preferred ED-PrEP were invited to participate in the study and provided written informed consent. At enrollment, participants received a bottle of co-formulated TDF 300 mg/FTC 200 mg; TenoEm (Thai Government Pharmaceutical Organization) and counseling on the ED-PrEP regimen. The ED-PrEP regimen involves a “2-1-1” schedule: loading two pills of TDF/FTC 2–24 h prior to sex and one pill 24 and 48 h afterward.⁹ Participants having sex on multiple consecutive days were recommended to extend dosing up to 48 h after the last sexual activity. Participants were monitored according to 2018 Thai National PrEP Guideline, including HIV testing in the following month and every 3 months thereafter, as well as creatinine and syphilis screening every 6 months.¹⁴ The participants’ blood samples were drawn for anti-HIV (electrochemiluminescence immunoassay, ECLIA), creatinine (enzymatic assay), and treponemal antibody (ECLIA) tests.

After enrollment, all participants were asked to attend clinic visits at Months 1, 3, and 6 and follow up by phone at Months 2, 4, and 5. At the Month 1, 3, and 6 follow-up visits, participants provided blood samples for anti-HIV testing. At each visit all sexual encounters and PrEP use were reviewed for accuracy in taking PrEP. Participants also received medication refills and ED-PrEP counselling. At Months 2, 4, and 5, all participants were interviewed over the phone about their PrEP use, including the accuracy and frequency of use, abnormal symptoms from STIs, and any adverse side effects. In between visits if participants had issues with PrEP use they had telephone access to staff that could arrange further care as needed, such as for post-exposure prophylaxis if ED-PrEP was taken incorrectly, having adverse events, or having symptoms of STD. Participants were counselled that if they would like to stop taking PrEP (if no HIV risk acquisition) or switch regimens to daily PrEP (if it is more appropriate according to sexual activity pattern) at any follow-up during the study period, they still be in a follow up visit of the study.

All participants were advised to download the mobile application “Raincoat”, produced by Focal Intelligence Co., Ltd. Based on the information-motivation‐behavioral (IMB) skills model,¹⁵ which consists of (1) information need related to HIV prevention (2) motivation of attitudes and intentions for HIV prevention by self-assessment of HIV risk acquistion, and (3) behavioral skills necessary for HIV prevention. It is aimed to support participants to regularly assess their HIV acquisition risk and to provide a schedule of taking ED-PrEP and appointment reminders.⁷ The application included a self‐evaluation feature for users to log numbers of sex acts, sexual partners, pills taken, and condom use, which were used to auto-calculate HIV risk.⁷ To facilitate ED-PrEP use, participants could record when they take the first two pills, which would then auto-generate reminders for the next two pills as notifications on their mobile phone. Reminder messages were customizable, not explicitly mentioning PrEP or HIV or taking medicine but a sentence such as “We have an appointment,” and users were able to set a password to ensure privacy. The Raincoat application was available on both Android OS and iOS mobile platforms.

Statistical analysis

Accuracy of and retention in ED-PrEP use, involves a “2-1-1” schedule: loading two pills of TDF/FTC 2–24 h prior to sex and one pill 24 and 48 h afterwards were the primary outcomes of this study. Follow-up time was set at 6 months to collect preliminary data on young ED-PrEP users in this study, however, services were offered beyond the study period. Retention was defined as the number of participants who continued using ED-PrEP for 6 months divided by the number of participants enrolled. ED-PrEP non-retention included switching regimens, ED-PrEP discontinuation, and loss to follow-up. Accuracy was defined as the number of person-months of correct ED-PrEP use divided by the total number of sexually active person-months. For a person-month to report “correct ED-PrEP use,” a participant must have administered ED-PrEP properly for all sex acts during the month. A person-month was considered “sexually active” if at least one sexual act occurred during the month. Both measures of retention and accuracy were presented as percentages with 95% confidence intervals (CI).

Descriptive statistics were used to characterize the data. Categorical variables were presented with absolute numbers and percentages, and continuous variables with medians and interquartile range (IQR). A Z-test for proportions was performed with an alpha-value of 0.05 to determine statistically significant differences. Stata/SE 13.0 was used for data analyses.

Results

A total of 36 YMSM consented to participate during the recruitment period from August 2020 to July 2021 with a median age of 18.7 (IQR, 17.5–19.4) years. At enrollment, all participants were in school, with 17 (47.3%) studying at the university level and 19 (52.7%) at the secondary level. Only five (13.9%) had work experience. Twenty-four (66.7%) were PrEP-naïve, and 12 had experience with but were not currently using PrEP. The proportion of complete follow-ups in the PrEP-naïve and PrEP-experienced groups were 22 of 24 (91.6%) and 10 of 12 (83.3%), respectively (p = 0.45).

Sexual activity and accuracy of ED-PrEP use

The 36 participants contributed 197 person-months during the 6 months of follow-up with an average of 0.6 (SD = 1.0) sex acts per month. Of the 197 person-months, 128 (65.0%) were reported as no sexual activity, with 9 participants (25%) reporting no sexual activities at all during the 6-month period. Of the 69 sexually active person-months which contributed from 27 participants, 38 (55.1%), 18 (26.1%), and 13 (18.8%) person-months involving one, two, and three or more sexual episodes, respectively (Figure 1). A total of 394 pills were administered during the 197 person-months, or a mean of two pills (SD = 3.6) per person-month, which corresponds with the average sexual activity of this population sample.

Figure 1.

Reported sexual activities among study participants.

Of the 69 sexually active person-months, 42 (60.9%; 95% CI = 48.4%–72.4%) reported correct ED-PrEP use. Reasons for 27 person-months of incorrect ED-PrEP use included: unplanned sexual activity, which was the most commonly cited reason, (n = 11; 40.7%), forgetting (n = 6; 22.2%); perceived as no risk for HIV acquisition (n = 5; 18.5%); side effects such as nausea, vomiting, or headache (n = 4; 14.8%); and misunderstanding the regimen (n = 1; 3.7%) (Table 1). Among the participants reporting an unplanned sexual encounter, 6 of 9 (66.7%) participated in receptive anal sex and could not dictate the event, and/or the event occurred in a party setting or while intoxicated.

Table 1.

Sexual activity, ED-PrEP use, and condom use presented in person-months.

Description	Sexually active: Person-months; % (95% CI)
	Correct use of ED-PrEP		Incorrect use of ED-PrEP
	100% condom use	Condomless at least once	100% condom use	Condomless at least once
Total follow up time, 197 person-months	42; 21.3% (15.8%–27.7%)		27; 13.7% (9.2%–19.3%)
Total follow up time, 197 person-months	31; 15.7% (10.9%–21.6%)	11; 5.6% (2.8%–9.8%)	17; 8.6% (5.1%–13.4%)	10; 5.1% (2.5%–9.1%)
Only sexually active month, 69 person- months	42; 60.9% (48.4%–72.4%)		27; 39.1% (27.6%–51.6%)
Only sexually active month, 69 person- months	31; 44.9% (32.9%–57.4%)	11; 15.9% (8.2%–26.7%)	17; 24.6% (15.0%–36.5%)	10; 14.5% (7.2%–25.0%)
Reasons for incorrect ED-PrEP use: reported from 27 person-months, n(%)
Unplanned sexual encounter			11; 40.7%
Forgot			6; 22.2%
Self-perceived as no risk			5; 18.5%
Side effects			4; 14.8%
Misunderstood regimen			1; 3.7%

ED-PrEP: event-driven pre-exposure prophylaxis; CI: confidence intervals.

Retention in ED-PrEP use

During the 6-month follow-up period, one participant from the PrEP-naïve group chose to discontinue PrEP at the month 1 follow-up because he had a single HIV-negative sexual partner and thus, no self-perceived risk. Three participants were lost to follow-up: one from the PrEP-naïve group was lost after the month 2 follow-up, and the other two from the PrEP-experienced group were lost after the month 1 and 2 follow-ups.

Thirty-two of 36 participants were retained in ED-PrEP for 6 months, an 88.9% (95% CI: 73.9%–96.9%) retention rate. No incident HIV infections occurred during the study period. One event of post-exposure prophylaxis (PEP) use was reported due to a broken condom and no PrEP use prior to the sexual encounter. Excluding non-sexual activity, loss to follow-up, and participants who discontinued PrEP, mean creatinine at baseline was 0.84 mg/dL (n = 21, 95% CI: 0.78–0.90) and 0.85 mg/dL at month 6 (n = 18, 95% CI: 0.79–0.91) (p = 0.86).

Condom use and sexually transmitted infections

Of the 69 sexually active person-months, 48 (69.6%) reported 100% condom use, with 73.8% and 63.0% falling under correct and incorrect ED-PrEP use, respectively (p = 0.34). (Table 1) Ten of the 69 (14.5%, 95% CI: 7.2%–25.0%) sexually active person-months were not protected from HIV/STIs by neither PrEP or condom use. Eleven of the 69 (15.9%, 95% CI: 8.2%–26.7%) sexually active person-months were in the condomless group but still protected by PrEP. Two of the 36 participants (5.6%) were infected with STIs during follow-up, both of whom were in the condomless group: one acquired syphilis from receptive anal sex and presented with genital ulcers (VDRL titer 1:16) while the other, N. gonorrhoeae urethritis from insertive anal sex, presenting with pyuria. Both participants and their partners were provided treatment and condoms.

Raincoat application use

Paradata from application showed that 22 of the 36 (61.1%) participants had ever logged in to Raincoat, especially during the first 4 months of the study. The most frequently used feature (n = 14, 63.6%) on Raincoat was “Sex Plan,” which reminds users when to take pills after they input their plan for sexual activity. Participant interviews revealed that 12 of the 36 (33.3%) consistently used the Raincoat application for medication reminders. Users reported that the application not only reminded them when to take PrEP on notification view, but also helped them schedule later doses based on planned sexual activities and determine when they should seek immediate help from the medical team. Fifteen of the 42 person-months of correct ED-PrEP use (35.7%; 95% CI: 21.2%–50.2%) reported use of Raincoat, compared to 4 of the 27 person-months of incorrect ED-PrEP use (14.8%; 95% CI: 1.4%–28.6%) (p = 0.06).

Discussion

This pilot study offers key insight on retention in and accuracy of ED-PrEP use. A higher proportion of participants (89%) was retained in the ED-PrEP program, compared to 73% retention in a same-length daily PrEP study among Thai YMSM and YTGW.⁷ A 2022 study of MSM in the US¹⁶ reported that on-demand PrEP was appropriate for MSM who were in the lower daily PrEP adherence quintiles or faced difficulty taking daily PrEP, with the on-demand regimen being similarly effective, even with fewer pills administered.¹⁶ This may be explained by the less demanding nature of ED-PrEP when compared to the once-daily regimen. The retention rates of our study and Songtaweesin et al.⁷ were substantially higher than those reported by the Princess PrEP Program,¹⁷ where retention in the ED-PrEP group was 22.3%, and 23.7% at months 3, and 6, respectively. This difference may be due to more frequent touchpoints (i.e. monthly, either by clinic visit or phone interview) and motivational interviewing by project staff in the present study and Songtaweesin et al.⁷

The participants of this study were enrolled if their sexual activity suited the WHO recommendation for ED-PrEP (i.e. sex fewer than two times per week on average).⁹ Indeed, our results reflected even lower average sexual activity, only once every 2 months. ED-PrEP would be most appropriate for them. This cohort also included 9 out of 36 (25%) abstinence from sexual activity during study period due to lockdowns and limited social interaction under the COVID-19 pandemic. Our study shows that it is feasible to prescribe ED-PrEP for at-risk Thai YMSM whose sexual activity is a fit for the regimen. Correct ED-PrEP use among YMSM in this study was relatively high (61%) compared to the IPERGAY trial¹⁰ (43%) and IPERGAY-OLE¹¹ (50%) but slightly lower than a study by Vuylsteke and colleagues (67%).¹⁸ Despite these promising results, ED-PrEP was administered incorrectly almost 40% of the time, often due to unplanned sexual encounters observed mostly among those participating in receptive anal sex, as they were not able to dictate the event, were at a party, and/or were intoxicated. In this group, loading the double dose (i.e. two pills) before partying or having unplanned sexual activity should be recommended. In a study exploring the potential of on-demand PrEP for YMSM in the US, 71% of participants did not know that they would have anal sex until less than 2 h beforehand, highlighting the need for interventions addressing the time-sensitive nature of ED-PrEP.²³ As reported by open-label studies in the US,^12,19–21 high adherence was found among participants who were aware of the importance of adherence to PrEP efficacy.

A study in Amsterdam found that 34.2% of participants switched between daily and ED-PrEP at least once in the 3-year period following PrEP initiation,²² further indicating that a more fluid PrEP regimen may be most suitable for real-world settings. One-third of participants in this study were previous daily PrEP users, but no participants switch from ED-PrEP to oral daily PrEP.

To help reduce common side effects such as headache, nausea, and vomiting, it is important to recommend that users take PrEP before bedtime. In terms of potential risk of renal impairment, we did not observe any change in serum creatinine level, which is consistent with iPrEx¹⁰ and IPERGAY¹⁴ studies. In the updated 2021 Thai National PrEP Guidelines, creatinine clearance is not required for monitoring participants under 30 years.¹

In this study, an average of four pills were taken every two person-months, which aligned with the number of sex acts (once every 2 months) appropriate for ED-PrEP use. Compared to the daily PrEP regimen, which requires 60 pills every two person-months, ED-PrEP is more cost-effective and better for overall health (e.g. fewer side effects), particularly among groups who have infrequent sex but are still at risk for HIV infection (e.g. YMSM).

Given the time-sensitive nature of ED-PrEP, mobile applications like Raincoat, which reminds users to take the two pills 24 and 48 h after the initial double dose, may prove particularly useful. In this study, there was a trend of higher rate of correct ED-PrEP user among participants who used RAINCOAT app than those who did not. However, the effects of the Raincoat application use on promoting correct ED-PrEP use are unclear, as only one-third of the participants consistently used the application, and frequent contact and PrEP counselling was already provided through monthly visits. In settings where personnel resources are constrained, Raincoat may offer a great source of support. We did not conduct qualitative interviews with participants to gauge the practicality of close monitoring (i.e. every month) while on ED-PrEP. In real-world settings without close monitoring, people may have higher rates of incorrect PrEP use and therefore, may need to prepare for PEP rescue.

Condom use was high among our sample, covering 70% of sexually active person-months. Only two of the 36 participants (5.6%) were infected with STIs during follow-up, both of whom were in the condomless group. The AMPrEP study²³ of MSM reported that STI incidence among ED-PrEP users was about 50% lower than among daily PrEP users, with fewer sexual partners, sex acts, and condomless anal sex acts with casual partners in the ED-PrEP group compared to the daily PrEP group.²³ However, 14.5% of sexually active person-months in our study were still protected by neither PrEP nor condoms, and STI incidence did occur among those who did not use condoms. This finding highlights that counseling on condom use is still essential to STI prevention. Past research²² has shown that the number of condomless anal sex acts increase over time, but since our study enrollees did not participate in frequent sexual activity, we were not able to validate this conclusion. Eleven of the 69 sexually active person-months in this study were in the condomless group, so ED-PrEP may have played an essential role in HIV protection, especially for those who did not prefer the daily regimen. ED-PrEP is currently considered as an alternative option for HIV prevention among MSM in the 2021 Thai National guideline.¹ Our study addresses a gap in the literature by focusing on ED-PrEP use among YMSM, not just MSM as a general population.^10,22 The lesson learned for the success of providing PrEP to adolescents include frequent engagement or touchpoints by either clinic visits or phone calls with a two way communication that participants can reach out to providers if any issue comes up such as requiring PEP rescue or STI symptoms. Furthermore, ED-PrEP is more suitable than oral daily PrEP for this population due to the low frequency of sexual activity. There were some limitations of this study, since the study was conducted during the COVID pandemic, and thus sexual activity among participants may be lower than usual due to social distancing and fear of COVID-19 infection. The follow up time of this study is only a 6-month period. However, we assumed that the proportion of correct use of ED-PrEP would remain, while participants gained more experience of using ED-PrEP.

Conclusions

ED-PrEP is feasible to implement successfully among Thai YMSM who have infrequent sexual encounters. Adequate information on how and when to administer ED-PrEP correctly is crucial to its effectiveness. Frequent contact is important for continued use, and a variety of avenues e.g. in-person clinic visits, telephone calls, virtual chat should be utilized. Moving forward, mobile applications such as Raincoat may play a more active role in promoting correct use of ED-PrEP.

Footnotes

Acknowledgements

The authors would like to acknowledge members of the study team: Pongpak Phongphiew, Nantika Paiboon, Napaporn Chantasrisawad, Pathariya Promsena, Krittaporn Pornpaisalsakul, Tuangtip Teerawit, and Patchareeyawan Srimuan. Special thanks to Pathomchai Amornratpaijit from The Center of Excellence for Pediatric Infectious Diseases and Vaccines for his support with finance and administrative management.

Author contributions

JT was responsible for writing the initial version of the manuscript. SK conducted the data analysis. SK, WS, and SV revised later versions of the manuscript. JT, AP, PW, and JM performed recruitment and appointment of participants and followed up for data collection. TP supervised the overall study operations, manuscript writing, and content. All authors have read and approved the final version of this manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Ratchadapisek Sompoch Endowment Fund (2021) under Telehealth Cluster, Chulalongkorn University. Surinda Kawichai is supported by C2F Fund, Ratchadapisek Somphot, Chulalongkorn University.

ORCID iDs

Jirawat Traikiatphum

Wipaporn N Songtaweesin

Surinda Kawichai

References

DoAaST Diseases . Thailand national guidelines for pre-exposure prophylaxis (PrEP) 2021. Nonthaburi: Department of Disease Control (TH); 2021.

Estimated HIV infections Thailand year 2020 [Internet], https://hivhub.ddc.moph.go.th/epidemic.php (2021, accessed 19 April 2021).

Lee

. Situational analysis of young people at high risk of HIV exposure in Thailand: synthesis report. Bangkok: UNICEF Thailand; 2015.

Thienkrua

van Griensven

Mock

, et al. Young men who have sex with men at high risk for HIV, Bangkok MSM Cohort study, Thailand 2006-2014. AIDS Behav 2018; 22(7): 2137–2146.

van Griensven

Thienkrua

McNicholl

, et al. Evidence of an explosive epidemic of HIV infection in a cohort of men who have sex with men in Thailand. Aids 2013; 27(5): 825–832.

Jose

JED

Sakboonyarat

Mungthin

, et al. Rising prevalence of HIV infection and associated risk factors among young Thai Men in 2018. Scientific Rep 2021; 11(1): 7796.

Songtaweesin

Kawichai

Phanuphak

, et al. Youth-friendly services and a mobile phone application to promote adherence to pre-exposure prophylaxis among adolescent men who have sex with men and transgender women at-risk for HIV in Thailand: a randomized control trial. J Int AIDS Soc 2020; 23(Suppl 5): e25564.

Service UPH . Preexposure Prophylaxis for the prevention of HIV infection in the United States – 2021 update a clinical practice guideline, https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf 2021.

Organization WH . What’s the 2+1+1? event-driven oral pre-exposure prophylaxis to prevent HIV for men who have sen with men: update to WHO’s recommendation on oral PrEP. Geneva: World Health Organization; 2019.

10.

Molina

Capitant

Spire

, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015; 373(23): 2237–2246.

11.

Molina

J-M

Charreau

Spire

, et al. Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study. The Lancet HIV 2017; 4(9): e402–e410.

12.

Molina

J-MGJ

Delaugerre

Pialoux

, et al. Incidence of HIV-infection with daily or on-demand oral PrEP with TDF/FTC in France [CROI Abstract 148]. In: Abstracts from the virtual CROI 2021 Conference on Retroviruses and Opportunistic Infections vCROI 2021 Abstract eBook. 2021.

13.

TMoP Health . Thai ministerial regulation, http://www.ratchakitcha.soc.go.th/DATA/PDF/2562/A/011/T_0004.PDF (2019, accessed 25 January 2019).

14.

Bureau of AIDS Tuberculosis and Sexually Transmitted Diseases, Department of Disease Control, Ministry of Public Health. Thailand National Guidelines for Pre-Exposure Prophylaxis: HIV-PrEP 2018 Nonthaburi: Department of Disease Control, Ministry of Public Health. 2018.

15.

Aliabadi

Carballo-Dieguez

Bakken

, et al. Using the information-motivation-behavioral skills model to guide the development of an HIV prevention smartphone application for high-risk MSM. AIDS Educ Prevent: Official Publication Int Soc AIDS Educ 2015; 27(6): 522–537.

16.

Sarah Stansfield

Boily

M-C

Hughes

, et al. Estimating benefits from using on-demand oral PrEP by MSM in a modeling study [CROI Abstract 836]. In: Abstracts From CROI 2022 Conference on Retroviruses and Opportunistic Infections CROI 2022 Abstract eBook, 2022.

17.

Gallagher

. Event-driven PrEP patients face retention issues in Thai study. In: International Aids Conference, https://www.contagionlive.com/view/eventdriven-prep-patients-face-retention-issues-thai-study (2020, accessed 9 July 2020).

18.

Vuylsteke

Reyniers

De Baetselier

, et al. Daily and event-driven pre-exposure prophylaxis for men who have sex with men in Belgium: results of a prospective cohort measuring adherence, sexual behaviour and STI incidence. J Int AIDS Soc 2019; 22(10): e25407.

19.

Grant

Anderson

McMahan

, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect Dis 2014; 14(9): 820–829.

20.

Liu

Cohen

Vittinghoff

, et al. Preexposure prophylaxis for HIV infection integrated with municipal- and community-based sexual health services. JAMA Intern Med 2016; 176(1): 75–84.

21.

Volk

Marcus

Phengrasamy

, et al. No new HIV infections with increasing use of HIV preexposure prophylaxis in a clinical practice setting. Clin Infect Dis 2015; 61(10): 1601–1603.

22.

Coyer

van den Elshout

MAM

Achterbergh

RCA

, et al. Understanding pre-exposure prophylaxis (PrEP) regimen use: Switching and discontinuing daily and event-driven PrEP among men who have sex with men. eClinicalMedicine 2020; 29-30: 100650.

23.

Hoornenborg

Coyer

Achterbergh

RCA

, et al. Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven pre-exposure prophylaxis in AMPrEP: 2 year results from a demonstration study. Lancet HIV 2019; 6(7): e447–e455.