On-demand Pre-exposure Prophylaxis Research Articles

Navigating patterns of oral PrEP use: A qualitative longitudinal study of gay, bisexual, and queer men's dynamic practices of pausing, on-demand, and stopping PrEP in Canada

The Canadian HIV pre-exposure prophylaxis (PrEP) guidelines recommend both daily and on-demand dosing for gay, bisexual, and queer men (GBQM), meeting additional risk criteria. However, limited research explored how GBQM implement pausing, on-demand, discontinuation, and resumption of PrEP, including the contextual factors affecting decision-making. Using a relationally situated implementation science framework, we examined how GBQM tailor PrEP use to changing social and sexual circumstances. We conducted 109 longitudinal interviews with current and former PrEP users from Ontario (n = 18) and British Columbia (n = 20), Canada, at three time points between 2020 and 2022. We identified three dynamic PrEP use trajectories: pausing, on-demand, and stopping. Pausing involved brief breaks followed by a return to daily use during heightened sexual activity. Others followed the 2-1-1 on-demand schedule, while some stopped PrEP with plans to resume if social and sexual circumstances change. During the COVID-19 pandemic, participants paused PrEP when sexual activities decreased, restarting daily use when sexual engagements resumed. Others paused due to relationship changes or sexual inactivity, resuming PrEP in anticipation of sex. On-demand PrEP was adopted to manage side effects or save costs. Some stopped PrEP for sustained periods due to monogamy, private insurance loss, side effects, or low perceived HIV risk. Participants expressed concerns regarding lack of information on these strategies, relying on online sources or peers for guidance. Most participants obtained enough PrEP knowledge to adapt use appropriately. Comprehensive education campaigns on adaptable PrEP use effectiveness and strategies to discontinue and resume PrEP for clinicians and GBQM should be implemented.

Incidence and Management of Complex Kidney Situations Among On-demand and Daily HIV Pre-exposure Prophylaxis Users.

Background: We evaluated complex pre-exposure prophylaxis (PrEP) situations linked to kidney issues in a cohort of on-demand and daily PrEP users. Setting: We conducted a single-center retrospective cohort study in France including all PrEP users who received a tenofovir disoproxil (TD)—emtricitabine (FTC) prescription between January 1, 2012 and December 31, 2019 with at least 1 creatinine measurement available before and after PrEP initiation. Methods: A complex kidney situation (CKS) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m2 on 2 consecutive measurements. We estimated the incidence of this event, described case management, and identified associated factors using a Cox model. Results: Three thousand one hundred and fourteen individuals were included in this study. Almost all were men (99%) with a median age of 35 years, 25% had an eGFR <90 mL/minute/1.73m2 at baseline, and 65% used on-demand PrEP. Nine users (0.29%) had a CKS at baseline; 8/9 initiated on-demand PrEP without renal function worsening after a median (interquartile range [IQR]) follow-up time of 14 months (7–31). Thirteen cases of CKS occurred during the follow-up for a 0.25 per 100 person-years incidence (95% confidence interval [CI]: [0.14; 0.45]). On-demand PrEP was used in 7/13 participants with no further episode of confirmed eGFR <60 mL/minute/1.73m2 after a 17-month median follow-up (IQR 4–18). CKS was associated with an age ≥50 years (hazard ratio [HR] 13, 95% CI: [4–39]) or with a baseline eGFR <90 mL/minute/1.73m2 (HR 34, 95% CI: [4–261]). 9/22 CKS were linked to high-protein intake for weight training. Conclusions: CKS were rare in our cohort. On-demand PrEP did not result in subsequent renal function worsening in these few situations.

On-Demand PrEP: Clinical Report of Pharmaceutical Care in HIV Pre-Exposure Prophylaxis

Introduction: Pre-Exposure Prophylaxis (PrEP) for HIV involves the combined use of antiretrovirals for individuals frequently exposed to HIV. Initially implemented in Brazil in 2018 with a daily dosing regimen of one pill, on-demand usage was recently (2022) incorporated into routine practice. Aim: To report the experience of providing pharmaceutical care to an on-demand PrEP patient in an outpatient pharmacy within Brazil's Unified Health System. Outlining: This experience report details of pharmaceutical care that included reception of the patient, conducting anamnesis, legally and technically prescription evaluation, dispensing PrEP with verbal guidance on potential adverse events related to pharmacotherapy, and scheduling a return visit to the service. Results: The patient was initially prescribed a daily regimen of PrEP. During the first return consultation, 30 days after starting PrEP, the patient reported adverse effects related to the gastrointestinal tract, leading to the recommendation of an on-demand PrEP regimen. Implications: As of the last pharmaceutical consultation (June 21, 2022), the patient maintained a negative HIV serology, was accustomed to the newly prescribed dosage, and reported reduced gastric discomfort associated with the use of on-demand PrEP. This facilitated adherence to pharmacotherapy and improved the preventive efficacy against HIV infection.

Strategies to Eliminate Inequity in PrEP Services in the US South and Rural Communities.

Inequity in preexposure prophylaxis (PrEP) care in the US South and rural communities is likely attributed to Social Determinants of Health and structural issues beyond individuals' control. We describe three approaches to modify PrEP care practice models to make access easier-"normalizing," "digitalizing," and "simplifying." "Normalizing" approaches are defined as practice models where medical providers who have access to PrEP candidates prescribe PrEP routinely (e.g., primary care providers, community pharmacists); these approaches are found to be highly applicable in real-world settings. Telehealth and other dHealth tools are examples of "digitalizing" PrEP, and their use has been increasing rapidly since the COVID-19 pandemic. "Simplifying" PrEP care (e.g., with HIV self-testing, on-demand PrEP) is highlighted in the most recent World Health Organization PrEP guideline. Identifying, implementing, and scaling up these new strategies can allow PrEP candidates to access it, potentially addressing inequities and promoting HIV risk reduction in the US South and rural communities.

Preferences for oral PrEP dosing among adolescent boys and young men in three sub-Saharan African countries.

HIV remains a leading contributor to the disease burden in sub-Saharan Africa, with adolescents and young people disproportionately affected. Optimising pre-exposure prophylaxis (PrEP) uptake has predominantly focused on women and adult men who have sex with men. We explore adolescent boys and young men's PrEP uptake preferences in South Africa, Uganda, and Zimbabwe. A cross-sectional sequential exploratory mixed-methods study amongst males aged 13-24 years was conducted between April and September 2019 as part of the CHAPS trial. Group discussions (GDs) and In-Depth Interviews (IDIs) focused on motivations and hindrances for HIV testing, PrEP preference, and reasons for the uptake of PrEP. A thematic approach was used to analyse the qualitative data. A quantitative survey following the qualitative work covered questions on demographics, HIV risk and PrEP preferences (on-demand vs. daily). For quantitative analysis, we fitted logistic regression models to determine factors associated with on-demand vs daily PrEP preference. Overall, 647 adolescent boys and young men (median age 20, IQR: 17-22) were enrolled. Of these, 422 (65.22%) preferred on-demand PrEP (South Africa 45.45%, Uganda 76.80%, Zimbabwe 70.35%; p<0.001). Factors independently associated with on-demand PrEP included country (South Africa, adjusted odds ratio (aOR) = 0.19 [95%CI:0.1-0.3] compared to Uganda) and advanced planning of sex [>24 hours in advance aOR = 1.4 (0.9-2.3) compared to <2 hours]. Qualitatively, participants commonly believed they were not at risk of HIV acquisition most of the time and thought that on-demand PrEP would be suitable as they tend to plan sexual activity in advance. Preference for on-demand PrEP is high in young males. The qualitative data support a preference for on-demand PrEP in those who plan sex in advance. HIV intervention programs should offer both on-demand and daily PrEP to engage more adolescent boys and young men in HIV prevention practices.

Prediction of Sex and the Potential Use of On-Demand PrEP Among Young Men Who Have Sex With Men in the U.S.

On-demand dosing of pre-exposure prophylaxis (PrEP) requires accurate prediction of sex; however, prediction abilities among young men who have sex with men (YMSM) have not been characterized. A nationally recruited prospective cohort of YMSM ages 16-24. We followed 120 YMSM for eight weeks using digital daily surveys (DDSs) to measure engagement in and prediction of anal sex over 24-hour periods, along with condom use and other encounter-level circumstances. Our main outcome, an "unpredicted spontaneous encounter," was defined as an anal sex encounter that occurred without sufficient prior knowledge to (hypothetically) enable protective on-demand PrEP use according to dosing guidelines. We operationalized this outcome as an anal sex encounter for which a participant indicated: a) on the prior day's DDS that there was a low likelihood of sex occurring in the subsequent 24 hours (unpredicted), and b) on the current day's DDS that he knew ≤2 hours in advance that the encounter would occur (spontaneous). Approximately one-third of all anal sex encounters during the study period were unpredicted and spontaneous and would not have been protected (hypothetically) by on-demand dosing. More than two-thirds of participants experienced such an encounter and almost three-quarters of all acts were condomless. On-demand PrEP to prevent HIV acquisition may be challenging for many YMSM. Clinical and public health approaches that account for patients' predictive abilities alongside their dosing preferences may help to optimize selection of and adherence to PrEP dosing strategies.

A qualitative study to explore daily versus on-demand oral pre-exposure prophylaxis (PrEP) in young people from South Africa, Uganda and Zimbabwe.

Adolescents in sub-Saharan Africa (SSA) remain vulnerable to HIV infection. While pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission as a daily or on-demand regimen, tailored approaches are necessary. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a mixed-methods research program investigating the acceptability and feasibility of implementing daily and on-demand PrEP among young people in SSA. It also aims to determine an on-demand dosing schedule for insertive sex. For this paper, we explored preferences for daily versus on-demand PrEP amongst adolescents as part of CHAPS. Purposive sampling was used to recruit participants from Soweto and Cape Town (South Africa), Wakiso district (Uganda) and Chitungwiza (Zimbabwe). At the time of the study in 2018/2019, Uganda had not rolled out PrEP to the general population; in Zimbabwe, PrEP for young people was only available at selected sites with one located within the study recruitment area. In South Africa, PrEP was made available to selected high-risk groups. We conducted 60 in-depth interviews and 24 group discussions amongst young people aged 13-24 without HIV in South Africa, Uganda, and Zimbabwe. All in-depth interviews and group discussions were audio-recorded, transcribed verbatim and translated to English. Data were analysed using framework analysis. The main themes were centered around preferences for daily and on-demand PrEP. Reasons for on-demand preferences included stigma, pill fatigue, adherence and side effects. Reasons for daily PrEP preferences included factors related to sexual risk behaviour, continuous protection against incidents of unintentional exposure, and the increased efficacy of a daily dose. Participants at all sites preferring daily PrEP identified the same reasons, with more males than females citing inadvertent blood contact or perceived increased efficacy. Similarly, participants at all sites preferring on-demand PrEP gave the same reasons for their preferences for on-demand PrEP; the exception was South Africans who did not mention the hope of having fewer side effects by not taking daily PrEP. Additionally, more males than females cited intermittent sex as a reason for opting for on-demand PrEP. Our study is the first known to explore and describe youth preferences for daily versus on-demand PrEP. While the choice is clear-cut, the reasons cited in the different options provide invaluable insights into their decisions, and the actual and perceived facilitators and barriers to access to PrEP. Further education is needed amongst young people, not only about PrEP but also in other areas of comprehensive sexuality education. Exploring all options of HIV prevention is crucial to provide a tailored, one-size-does-not-fit-all approach to adolescent care in SSA to reduce and, the continued and increasing risk of this preventable infection.

The Use of Daily and On-Demand Oral Pre-Exposure Prophylaxis Dosing Strategies Among Young Adult Gay, Bisexual and Other Men who have Sex with Men Enrolled in an mHealth Adherence Intervention.

Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention option for gay, bisexual and other men who have sex with men (GBMSM). However, with newer PrEP options, a greater understanding of whether and why GBMSM switch dosing strategies is needed to inform clinical practice and research. We assessed the dosing strategies (daily or on-demand) of GBMSM enrolled in an mHealth PrEP adherence pilot intervention at four timepoints over approximately 10 months. Among GBMSM with complete data (n = 66), a consistent daily dosing strategy was used by most (73%) participants across all time points, while on-demand PrEP was used at least once during the study period by 27% of participants. A higher percentage of on-demand PrEP users self-reported as Asian/Pacific Islander and had less positive attitudes toward PrEP, adjusting for key sociodemographic variables and intervention arm. Daily PrEP users reported high numbers of sexual partners, and the primary reason that they would switch to on-demand PrEP is reduced sexual activity. At the final assessment, 75% of participants were taking daily PrEP, of whom 27% reported that they would like to switch to another option, including on-demand and long-acting injectable PrEP. While findings were largely descriptive, they showed that switches in PrEP dosing strategies are relatively common and PrEP strategy choice may vary across racial and ethnic groups.

Estimating benefits of using on-demand oral prep by MSM: a comparative modeling study of the US and Thailand

Daily and on-demand pre-exposure prophylaxis (PrEP) are effective at preventing HIV acquisition among men who have sex with men (MSM), but only daily PrEP is approved in the US. On-demand PrEP may improve uptake and adherence. We identify sub-groups of MSM who would benefit from on-demand PrEP and determine effectiveness achieved if individuals used their optimal regimens. Using data from the HPTN 067 study (study period 2012-2014), we created an individual-based stochastic model of HIV risk in two synthetic MSM populations with parameters separately estimated using data from Harlem, US, and Bangkok, Thailand. Agents were assigned daily and on-demand PrEP for six months each. Two personalized PrEP assignments: optimal, based on improved predicted effectiveness and reduced pill burden, and adherence-based, using daily PrEP adherence, were simulated for another six months. Simulated on-demand PrEP was optimal for approximately one-third of MSM. It was assigned mainly to those with low daily PrEP adherence (88% (Harlem), 95% (Bangkok) of MSM with daily PrEP adherence <40%). Mean effectiveness was slightly higher in the full synthetic population with optimal PrEP assignment compared to universal daily PrEP. Among MSM for whom on-demand PrEP was optimal, mean effectiveness improved by 18 (Harlem) and 7 percentage points (Bangkok). Comparable predicted effectiveness was achieved if on-demand PrEP was assigned to the population with daily PrEP adherence <50%. There was no advantage in assigning on-demand PrEP by sex act frequency. On-demand PrEP could benefit many MSM by increasing effectiveness or decreasing pill burden with similar effectiveness. On-demand PrEP may be an effective alternative to daily PrEP for individuals with difficulty taking daily PrEP consistently. Results were similar for Harlem and Bangkok, indicating that these conclusions were robust in populations with different overall adherence levels and may inform future public-health policies. US NIH grant UM1 AI068617.

Self-start HIV postexposure prophylaxis (PEPSE), to reduce time to first dose and increase efficacy

BackgroundEffectiveness of HIV postexposure prophylaxis (PEPSE) correlates with speed of uptake following HIV exposure. Time to first dose has not improved in the UK for over 10 years. On-demand pre-exposure...

2089. Relative patient preferences for starting daily, on-demand, and long-acting injectable HIV pre-exposure prophylaxis among US men who have sex with men, 2021-2022

Abstract Background Daily oral (DO) HIV pre-exposure prophylaxis (PrEP) effectively prevents HIV acquisition, but few men who have sex with men (MSM) currently use it. Newer options, such as on-demand (OD) oral and long-acting injectable (LA) PrEP may improve uptake, but little is understood about relative preferences among these options in practical start scenarios. Preferences for starting various PrEP options were examined among a US nationwide online convenience sample of MSM age 15+ collected September 2021 to February 2022. Methods Participants reporting no prior HIV diagnosis were given brief descripitions of each PrEP option and were asked “If [PrEP option] were available from your local doctor and you could access it for free, would you go to your doctor in the next month to start [PrEP option]?” Those who said yes to multiple options were asked to rank them in order of preference. MSM currently taking DO PrEP were asked whether they would switch to OD or LA. Willingness to start LA was examined by age, race/ethnicity, insurance, and prior awareness of LA. Results Of 5585 MSM not currently using DO PrEP, 50% (n=2805) would start at least one option with greatest preference for OD (Figure 1). Among this group, 73% (n=2060) were willing to start more than one option, with LA the most preferred option. Among the 27% (n=745) who would start only one, OD was the most preferred. Overall, 58% of DO PrEP users (n=1342/2332) would switch to either OD or LA, with LA being most preferred (Figure 2). Hispanic MSM who were not DO PrEP users were more likely to start LA compared to white MSM, and those with other/multiple health insurance were less likely to start LA compared to those on private health insurance (Table 1). Regardless of current DO PrEP use, MSM aware of LA were more likely to start it. Conclusion There is substantial interest in new PrEP options. Current DO PrEP users appear to be more aware of and interested in LA than PrEP naïve. Although OD PrEP may be favored by those who are PrEP-naïve, most selected multiple options and preferred LA PrEP. Increasing awareness of LA PrEP may bolster interest in its use. These findings highlight the potential role that newer PrEP options will play in community uptake of PrEP and can also inform patient-provider decisions about which PrEP options to consider. Disclosures Travis Sanchez, DVM, MPH, ViiV Healthcare: Grant/Research Support S. Wilson Beckham, PhD, MPH, MA, Viiv Healthcare: Advisor/Consultant Keith Rawlings, MD, ViiV Healthcare: Employee Alex R. Rinehart, PhD, ViiV Healthcare: Stocks/Bonds Supriya Sarkar, PhD, MPH, ViiV Healthcare: Salary|ViiV Healthcare: Stocks/Bonds Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds.

Pharmacokinetics and efficacy of topical inserts containing tenofovir alafenamide fumarate and elvitegravir administered rectally in macaques.

Topical on-demand forms for HIV pre-exposure prophylaxis (PrEP) may be a desirable alternative for people that prefer not to use daily PrEP. CONRAD has developed inserts containing tenofovir alafenamide (TAF) and elvitegravir (EVG) for on-demand vaginal or rectal pericoital use. We assessed the pharmacokinetics (PK) and pre-exposure efficacy of rectally applied TAF/EVG inserts in macaques. PK was assessed in 12 pigtailed macaques. Tenofovir (TFV) and EVG levels were assayed in rectal biopsies and secretions, and tenofovir-diphosphate (TFV-DP) levels in biopsies and peripheral blood mononuclear cells (PBMC). Drug biodistribution was evaluated in 10 animals at necropsy 4 h post-dosing. For efficacy assessments, one or two TAF/EVG inserts were administered to macaques (n=6) 4 h before repeated rectal SHIV162p3 challenges. One TAF/EVG insert resulted in rapid and high EVG and TFV-DP in rectal tissue 4 h after application. Adding a second insert led to a 10-fold increase in EVG and TFV-DP in rectal tissue. Efficacy of one and two TAF/EVG inserts were 72.6% (CI 24.5%-92.6%) and 93.1% (CI 73.3%-99.2%), respectively. Although high TFV-DP and EVG levels were observed with one rectal TAF/EVG insert, it only conferred partial protection from rectal SHIV challenges. Adding a second insert led to an increase in TFV and EVG in rectal tissues resulting in higher (>90%) efficacy. These results highlight the high efficacy of TAF/EVG inserts as topical on-demand rectal PrEP, as well as the need for appropriate drug coverage in the deep rectum and colon to achieve high protection. The work related to animal studies was funded by CDC intramural funds and an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002). The work related to the insert formulation was funded by U.S. PEPFAR through USAID under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School. The findings and conclusions of this manuscript are those of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC), USAID, President's Emergency Plan for AIDS Relief (PEPFAR), Eastern Virginia Medical School (EVMS), or the US government.

Single dose topical inserts containing tenofovir alafenamide fumarate and elvitegravir provide pre- and post-exposure protection against vaginal SHIV infection in macaques.

Vaginal products for HIV prevention that can be used on-demand before or after sex may be a preferable option for women with low frequency or unplanned sexual activity or who prefer not to use daily or long-acting pre-exposure prophylaxis (PrEP). We performed dose ranging pharmacokinetics (PK) and efficacy studies of a vaginally applied insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) in macaques under PrEP or post-exposure prophylaxis (PEP) modalities. PK studies were performed in 3 groups of pigtailed macaques receiving inserts with different fixed-dose combinations of TAF and EVG (10/8, 20/16 and 40/24mg). PrEP and PEP efficacy of a selected insert was investigated in a repeat exposure vaginal SHIV transmission model. Inserts were administered 4 h before (n=6) or after (n=6) repeated weekly SHIV exposures. Infection outcome was compared with macaques receiving placebo inserts (n=12). Dose ranging studies showed rapid and sustained high drug concentrations in vaginal fluids and tissues across insert formulations with minimal dose proportionality. TAF/EVG (20/16mg) inserts were selected for efficacy evaluation. Five of the 6 animals receiving these inserts 4 h before and 6/6 animals receiving inserts 4 h after SHIV exposure were protected after 13 challenges (p=0.0088 and 0.0077 compared to placebo, respectively). The calculated PrEP and PEP efficacy was 91.0% (95% CI=32.2%-98.8%) and 100% (95% CI=undefined), respectively. Inserts containing TAF/EVG provided high protection against vaginal SHIV infection when administered within a 4 h window before or after SHIV exposure. Our results support the clinical development of TAF/EVG inserts for on-demand PrEP and PEP in women. Funded by CDC intramural funds, an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002), and by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID) under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School.

Intimate Partner Violence and Willingness to Use Pre-Exposure Prophylaxis Among Men Who Have Sex With Men in Chengdu, China.

Intimate partner violence (IPV) is common in men who have sex with men (MSM). MSM also face increased risk of human immunodeficiency virus infection. However, it is not known whether IPV experience of MSM in China would affect their attitudes toward pre-exposure prophylaxis (PrEP) use. A cross-sectional study was conducted to explore the associations between different types of IPV and willingness to use PrEP in a sample of 608 MSM from November 2018 to May 2019 in Chengdu, China. Univariate and multivariate logistic regression analyses were used to explore the associations between different types of IPV and willingness to use PrEP. The average age of the participants was 31.8 ± 12.3 years, 48.9% of them were aware of PrEP before this study, and only 7.2% were aware of long-acting injectable PrEP (LAI-PrEP). The overall willingness to use any type of PrEP in the next 6 months was 82.2%. Approximately one third of the participants (n = 198) had experienced at least one type of IPV. We found that experience of sexual perpetration was negatively associated with the willingness to use on-demand PrEP (adjusted odds ratio [ORa] = 0.33, 95% CI = 0.16-0.67) and the overall willingness to use any type of PrEP (ORa = 0.31, 95% CI = 0.15-0.64). The willingness to use LAI-PrEP also had negative associations with any type of monitoring IPV (ORa = 0.58, 95% CI = 0.38-0.91), controlling victimization (ORa = 0.41, 95% CI = 0.21-0.82), and emotional victimization (ORa = 0.58, 95% CI = 0.35-0.97). The findings of this study demonstrate that IPV experiences are negatively associated with willingness to use PrEP among MSM, suggesting that PrEP promotion programs should consider IPV screening and develop explicit intervention strategies for both perpetrators and victims.

Willingness to use the three types of pre-exposure prophylaxis and associated factors among men who have sex with men in Chengdu

Objective: To investigate the willingness to use three types of pre-exposure prophylaxis (PrEP) and its associated factors among MSM in Chengdu. Methods: A total of 793 MSM were recruited through Chengdu Tongle Health Consultation Service Centre between November 2021 to January 2022. Data were collected, including demographic characteristics, sexual behaviors in the last six months, PrEP-related stigma, HIV anticipated stigma, MSM internalized stigma, and willingness to use three types of PrEP. Univariate and multivariate logistic regression models were conducted to investigate the associated factors of willingness in using the three types of PrEP. Results: Among 793 participants, willingness to take on-demand PrEP was higher (68.3%). Higher education and multiple sexual partners increased the willingness to use oral PrEP, higher education [compared with junior high school or below, high school or technical secondary school (aOR=2.43, 95%CI: 1.13-5.21), junior college (aOR=2.67, 95%CI: 1.27-5.61), bachelor degree (aOR=3.21, 95%CI: 1.52-6.74), master degree or above (aOR=3.77, 95%CI: 1.54-9.26)], multiple sexual partners (aOR=1.54, 95%CI: 1.12-2.11) were positively associated with daily oral PrEP. HIV anticipated stigma was positively associated with the willingness in using all three types of PrEP: daily oral PrEP (aOR=1.07, 95%CI: 1.02-1.12), on-demand PrEP (aOR=1.09, 95%CI: 1.03-1.15), and injectable PrEP every 8 week (aOR=1.06, 95%CI: 1.01-1.11). Conclusions: The overall willingness in using PrEP in MSM in Chengdu is relatively high, and the promotion of PrEP is highly feasible. In the future, we should continue to promote publicity and education on HIV and PrEP-related knowledge in this population, improve the cognitive level, and guide MSM to establish the correct motivation for PrEP use.

Impact on renal function of daily and on-demand HIV pre-exposure prophylaxis in the ANRS-PREVENIR study.

To assess the impact on the estimated glomerular filtration rate (eGFR) of different tenofovir disoproxil/emtricitabine dosing regimens for HIV pre-exposure prophylaxis (PrEP). We included in the study individuals with baseline eGFR > 50 mL/min/1.73 m2 who initiated PrEP in the ongoing ANRS-PREVENIR PrEP cohort. We retrospectively classified PrEP users in three groups: 'on-demand' (reported at ≥75% of study visits), 'daily' (≥75% of study visits) or 'switches'. We compared the area under curve (AUC) of the eGFR variation from baseline (ΔeGFR) between groups using analysis of covariance, and assessed factors associated with a negative AUC of ΔeGFR. From May 2017 to October 2020, 1253 PrEP-naïve participants (98% of MSM) were included in the study with a median follow-up of 22 months. 499 (40%), 494 (39%) and 260 (21%) users were in the group daily, on-demand and switches, respectively, for a median number of pills taken per week of 6, 1.7 and 4. The mean AUC of the ΔeGFR was -1.09 mL/min/1.73 m2 in the daily PrEP group, -0.69 mL/min/1.73 m2 in the switches group and +0.18 mL/min/1.73 m2 with on-demand PrEP. In a model adjusted on baseline age and eGFR, the AUC of the ΔeGFR was significantly higher with on-demand PrEP compared to daily PrEP (P = 0.037). Independent factors associated with a negative AUC of ΔeGFR were a daily PrEP regimen, a switches regimen, an age > 40 years and a baseline eGFR≥90 mL/min/1.73 m². On-demand PrEP dosing had a smaller impact on eGFR evolution than daily PrEP, but the difference was not clinically relevant.

A multi-country cross-sectional study to assess predictors of daily versus on-demand oral pre-exposure prophylaxis in youth from South Africa, Uganda and Zimbabwe.

IntroductionSub‐Saharan Africa (SSA) carries the burden of the HIV epidemic, especially among adolescents and young people (AYP). Little is known about pre‐exposure prophylaxis (PrEP) uptake and preferences among AYP in SSA. We describe preferences for daily and on‐demand PrEP among AYP in South Africa, Uganda and Zimbabwe.MethodsA cross‐sectional survey was conducted in 2019 among 13‐ to 24‐year olds, capturing socio‐demographics, HIV risk behaviours and preferences for daily or on‐demand PrEP. Logistic regression models were used to estimate odds ratios, adjusting for site, sex and age.Results and discussionA total of 1330 participants from Cape Town (n = 239), Johannesburg (n = 200), Entebbe (n = 491) and Chitungwiza (n = 400) were enrolled; 673 (51%) were male, and the median age was 19 years (interquartile range 17–22 years). Of 1287 participants expressing a preference, 60% indicated a preference for on‐demand PrEP with differences by site (p < 0.001), sex (p < 0.001) and age group (p = 0.003). On‐demand PrEP was most preferred in Entebbe (75%), among males (65%) versus females (54%) and in older participants (62% in 18‐ to 24‐year‐olds vs. 47% in 13‐ to 15‐year‐olds). After adjusting for site, sex and age group, preference for on‐demand PrEP decreased as sex frequency over the past month increased (p‐trend = 0.004) and varied with the number of partners in the last 6 months, being least popular among those reporting four or more partners (p = 0.02). Participants knowing further in advance that they were likely to have sex were more likely to prefer on‐demand PrEP (p‐trend = 0.02). Participants having a larger age gap with their most recent partner and participants whose last partner was a transactional sex partner or client were both less likely to prefer on‐demand compared to daily PrEP (p = 0.05 and p = 0.09, respectively). Participants who knew their most recent partner was living with HIV or who did not know the HIV status of their most recent partner were less likely to prefer on‐demand PrEP (p = 0.05).ConclusionsOur data show that AYP in four SSA communities prefer on‐demand over daily PrEP options, with differences seen by site, age and sex. PrEP demand creation needs to be reviewed, optimized and tailored to socio‐demographic differences and designed in conjunction with AYP.

PrEP user profiles, dynamics of PrEP use and follow-up: a cohort analysis at a Belgian HIV centre (2017-2020).

IntroductionThe number of individuals initiating antiretroviral pre‐exposure prophylaxis (PrEP) is increasing, but we do not fully understand who is coming forward for PrEP, how they use it and how they are followed‐up. The objective of this study was to examine PrEP user profiles, dynamics in PrEP use and follow‐up over time.MethodsWe conducted a cohort analysis of longitudinally collected clinical record and questionnaire data among PrEP users at an HIV centre in Antwerp, Belgium, between June 2017 and March 2020. PrEP follow‐up and user profiles were examined using descriptive analyses and bivariate logistic regression. We compared early adopting PrEP users (started before June 2018) with late users. We also calculated the probabilities of switching between daily and on‐demand PrEP, and interruption, using a naïve estimator.Results and discussionWe included 1347 PrEP users in the analysis. After 12 months, retention in care was 72.3%. Median time between PrEP visits was 98 days (IQR 85–119 days). At screening visit, early adopting PrEP users (starting June 2017–May 2018) were significantly more likely to report one or more sexually transmitted infection in the prior 12 months, having used drugs during sex, a higher number of sexual partners and a history of paid sex and PrEP use prior to initiation, compared with PrEP users who initiated later (starting June 2018–February 2020). When taking PrEP daily, the probability of staying on daily PrEP at the next visit was 76%, while this was 73% when taking PrEP on‐demand. Those using on‐demand PrEP had a higher probability (13%) of interrupting PrEP care than daily PrEP users (7%), whereas those returning to PrEP care would mostly re‐start with on‐demand (35% vs. 13% for daily).ConclusionsThe majority of PrEP users in this sample remained in care after 12 months. The probability of remaining on the same PrEP regimen at the subsequent visit was high. Though, we observed a diversity of transitions between regimens and interruptions in between visits. Our findings reaffirm the need to provide tailored PrEP services, counselling PrEP users across their life course.

Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study

There are few data available regarding the use of on-demand pre-exposure prophylaxis (PrEP) for HIV prevention. We aimed to assess PrEP effectiveness, adherence, and safety in adults using daily or on-demand PrEP. We conducted a prospective observational cohort study (ANRS PREVENIR) at 26 sites in the Paris region, France. We enrolled HIV-negative adults (aged ≥18 years) at high risk of HIV infection who were starting or continuing PrEP. PrEP was prescribed as a fixed-dose combination of tenofovir disoproxil and emtricitabine (245 mg and 200 mg, respectively, per pill). PrEP could be prescribed as a daily regimen with one pill per day or, in men who have sex with men (MSM) or in transgender women who have sex with men, as an on-demand regimen following the IPERGAY dosing recommendation. At enrolment and every 3 months thereafter, participants were tested for HIV and provided information regarding the PrEP dosing regimen used. Adherence to PrEP was assessed by self-report and by tenofovir diphosphate concentrations in dried blood spots. The primary outcome of HIV-1 incidence was assessed using Poisson regression among participants who started PrEP. This study is registered with ClinicalTrials.gov, NCT03113123, and EudraCT, 2016A0157744. Between May 3, 2017, and May 2, 2019, 3082 people were assessed for eligibility and 3065 participants were enrolled. 3056 (99·7%) of 3065 participants reported using PrEP and were included in the analyses. The median age was 36 years (IQR 29-43), 1344 (44·0%) of 3056 participants were PrEP-naive, and 3016 (98·7%) were MSM. At enrolment, 1540 (50·5%) of 3049 participants opted for daily PrEP dosing and 1509 (49·5%) opted for on-demand PrEP dosing; these proportions remained stable during follow-up. Median follow-up was 22·1 months (IQR 15·9-29·7) and incidence of study discontinuation was 17·6 participants (95% CI 16·5-18·7) per 100 person-years. At the data cutoff on Sept 30, 2020, there had been six HIV-1 seroconversions (three participants using daily PrEP and three using on-demand PrEP; all were MSM) over 5623 person-years. Overall HIV-1 incidence was 1·1 cases (95% CI 0·4-2·3) per 1000 person-years, and did not differ between participants using daily PrEP and those using on-demand PrEP (incidence rate ratio 1·00, 95% CI 0·13-7·49; p=0·99). Four participants (two using daily PrEP and two using on-demand PrEP) discontinued PrEP due to treatment-related adverse events (nausea [n=2], vomiting and diarrhoea [n=1], and lumbar pain [n=1]). In this study, which enrolled mainly MSM, HIV-1 incidence on PrEP was low and did not differ between participants using daily PrEP and those using on-demand PrEP. On-demand PrEP therefore represents a valid alternative to daily PrEP for MSM, providing greater choice in HIV prevention. ANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France. For the French translation of the abstract see Supplementary Materials section.

Evidence supports use of on-demand PrEP for HIV prevention

Daily oral pre-exposure prophylaxis (PrEP) is a highly effective biomedical intervention for reducing the risk of acquiring HIV and has been approved and recommended by several health authorities, such as WHO and the US Centers for Disease Control and Prevention. On-demand (or event-driven) PrEP has also been shown to be highly effective in preventing HIV, although there are fewer data and therefore less evidence to support this dosing regimen, and it is recommended only in cisgender men who have sex with men (MSM).