Supriya Sarkar

Background: Transfeminine persons in the United States face a high burden of human immunodeficiency virus (HIV), yet national data on preexposure prophylaxis (PrEP) use remain limited. We examined PrEP utilization, adherence, and persistence and reasons for never using PrEP among a national sample of transfeminine persons. Methods: Sexually active transfeminine persons aged ≥15 years without HIV were recruited online through the Transgender Women's Internet Survey and Testing (TWIST) Study, a national cross-sectional survey conducted between June 2023 and October 2024. Multivariable Poisson regression was used to estimate adjusted prevalence ratios for characteristics associated with current PrEP use. Reasons for never using PrEP were examined descriptively by age group. Results: Among 1656 participants, 6% were currently using PrEP and 86% had never used PrEP. Among current users (n = 96), 94% used oral PrEP and 6% used long-acting injectable (LA) PrEP. Among the 32 participants who reported using <30 daily PrEP doses in the past 30 days, 25% indicated that they were using event-driven (on-demand) PrEP, taking it only when they anticipated having sex. In multivariable models, current PrEP use was higher among participants aged ≥40 years, Black participants, and participants reporting a sexually transmitted infection diagnosis, multiple sexual partners, illicit drug use, or prescribed medication use. Common reasons for never using PrEP among participants aged 15–24 years included insurance-related privacy and disclosure concerns and transportation barriers, while among participants aged ≥25 years, reasons included loss of insurance, side-effect concerns, and monogamous partnerships. Conclusions: PrEP uptake among transfeminine persons remains low, with distinct age-specific barriers. Tailored interventions are needed. LA PrEP may help address challenges related to adherence and disclosure, particularly among younger individuals.

Background: Long-acting (LA) injectable preexposure prophylaxis (PrEP) and on-demand PrEP may improve overall PrEP uptake among men who have sex with men (MSM), but little is understood about the PrEP option preferences of MSM in practical scenarios where they may choose between various PrEP options. Objective: This study aims to examine the preferences for starting various PrEP options among a US nationwide online convenience sample of MSM from September 2021 to February 2022. Methods: Participants reporting no prior HIV diagnosis were provided brief descriptions 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 daily oral (DO) PrEP were asked whether they would switch to on-demand or LA PrEP options. Log binomial models were created to examine the association between willingness to start or switch to on-demand and LA PrEP with various sociodemographic and behavioral factors. Results: In the analytic sample (N=7760), among the participants who did not use any PrEP in the past 12 months (n=5108, 66%), 54% (n=2445) reported willingness to start at least 1 PrEP option and 41% (n=1845) of participants showed interest in starting multiple PrEP options. Overall, the highest willingness was reported for on-demand PrEP (n=2235, 44%), followed by DO PrEP (n=2174, 43%) and LA PrEP (n=1482, 29%). LA PrEP was ranked first among those interested in multiple options. Characteristics associated with ranking LA PrEP as a first option to start PrEP versus DO or on-demand PrEP were region of residence (residing in the West vs Northeast), report of sexually transmitted infection diagnosis in the past year, report of illicit drug use other than marijuana in the past year, and prior awareness of LA PrEP. Among current DO PrEP users (n=2379, 31%), 58% (n=1386) were willing to switch to on-demand or LA PrEP, and LA PrEP was ranked first among participants who were open to switching to both options. Willingness to switch to LA PrEP was higher among those who used illicit drugs other than marijuana in the past year, who heard of LA PrEP prior to the survey, and those who took 15 or less doses of oral PrEP in the last 30 days. Conclusions: LA PrEP was the highest-ranked option among most MSM who were willing to try multiple options or switch from DO PrEP. These findings highlight that LA PrEP might fill coverage gaps among MSM who use illicit drugs, have had a recent sexually transmitted infection diagnosis, and have less than optimal DO PrEP adherence.

BACKGROUND Long-acting (LA) injectable preexposure prophylaxis (PrEP) and on-demand PrEP may improve overall PrEP uptake among men who have sex with men (MSM), but little is understood about the PrEP option preferences of MSM in practical scenarios where they may choose between various PrEP options. OBJECTIVE This study aims to examine the preferences for starting various PrEP options among a US nationwide online convenience sample of MSM from September 2021 to February 2022. METHODS Participants reporting no prior HIV diagnosis were provided brief descriptions 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 daily oral (DO) PrEP were asked whether they would switch to on-demand or LA PrEP options. Log binomial models were created to examine the association between willingness to start or switch to on-demand and LA PrEP with various sociodemographic and behavioral factors. RESULTS In the analytic sample (N=7760), among the participants who did not use any PrEP in the past 12 months (n=5108, 66%), 54% (n=2445) reported willingness to start at least 1 PrEP option and 41% (n=1845) of participants showed interest in starting multiple PrEP options. Overall, the highest willingness was reported for on-demand PrEP (n=2235, 44%), followed by DO PrEP (n=2174, 43%) and LA PrEP (n=1482, 29%). LA PrEP was ranked first among those interested in multiple options. Characteristics associated with ranking LA PrEP as a first option to start PrEP versus DO or on-demand PrEP were region of residence (residing in the West vs Northeast), report of sexually transmitted infection diagnosis in the past year, report of illicit drug use other than marijuana in the past year, and prior awareness of LA PrEP. Among current DO PrEP users (n=2379, 31%), 58% (n=1386) were willing to switch to on-demand or LA PrEP, and LA PrEP was ranked first among participants who were open to switching to both options. Willingness to switch to LA PrEP was higher among those who used illicit drugs other than marijuana in the past year, who heard of LA PrEP prior to the survey, and those who took 15 or less doses of oral PrEP in the last 30 days. CONCLUSIONS LA PrEP was the highest-ranked option among most MSM who were willing to try multiple options or switch from DO PrEP. These findings highlight that LA PrEP might fill coverage gaps among MSM who use illicit drugs, have had a recent sexually transmitted infection diagnosis, and have less than optimal DO PrEP adherence.

In 1995, journalist Gary Taubes published an article inSciencetitled “Epidemiology faces its limits,” which questioned the utility of nonrandomized epidemiologic research and has since been cited more than 1000 times. He highlighted numerous examples of research topics he viewed as having questionable merit. Studies have since accumulated for these associations. We systematically evaluated current evidence of 53 example associations discussed in the article. Approximately one-quarter of those presented as doubtful are now widely viewed as causal based on current evaluations of the public health consensus. They include associations between alcohol consumption and breast cancer, residential radon exposure and lung cancer, and the use of tanning devices and melanoma. This history should inform current debates about the reproducibility of epidemiologic research results.

Introduction: Over one hundred implementation studies of HIV pre‐exposure prophylaxis (PrEP) are completed, underway or planned. We synthesized evidence from these studies to inform mathematical modelling of the prevention cascade for oral and long‐acting PrEP in the setting of western Kenya, one of the world’s most heavily HIV‐affected regions.Methods: We incorporated steps of the PrEP prevention cascade – uptake, adherence, retention and re‐engagement after discontinuation – into EMOD‐HIV, an open‐source transmission model calibrated to the demography and HIV epidemic patterns of western Kenya. Early PrEP implementation research from East Africa was used to parameterize prevention cascades for oral PrEP as currently implemented, delivery innovations for oral PrEP, and future long‐acting PrEP. We compared infections averted by PrEP at the population level for different cascade assumptions and sub‐populations on PrEP. Analyses were conducted over the 2020 to 2040 time horizon, with additional sensitivity analyses for the time horizon of analysis and the time when long‐acting PrEP becomes available.Results: The maximum impact of oral PrEP diminished by over 98% across all prevention cascades, with the exception of long‐acting PrEP under optimistic assumptions about uptake and re‐engagement after discontinuation. Long‐acting PrEP had the highest population‐level impact, even after accounting for possible delays in product availability, primarily because its effectiveness does not depend on drug adherence. Retention was the most significant cascade step reducing the potential impact of long‐acting PrEP. These results were robust to assumptions about the sub‐populations receiving PrEP, but were highly influenced by assumptions about re‐initiation of PrEP after discontinuation, about which evidence was sparse.Conclusions: Implementation challenges along the prevention cascade compound to diminish the population‐level impact of oral PrEP. Long‐acting PrEP is expected to be less impacted by user uptake and adherence, but it is instead dependent on product availability in the short term and retention in the long term. To maximize the impact of long‐acting PrEP, ensuring timely product approval and rollout is critical. Research is needed on strategies to improve retention and patterns of PrEP re‐initiation.

Background: Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) is reportedly efficacious, although full trial results have not been published. We used a dynamic network model of HIV transmission among men who have sex with men (MSM) to assess the population impact of LAI-PrEP when available concurrently with daily-oral (DO) PrEP. Methods: The reference model represents the current HIV epidemiology and DO-PrEP coverage (15% among indicated) among MSM in the southeastern US. Primary analyses investigated varied PrEP uptake and proportion selecting LAI-PrEP. Secondary analyses evaluated uncertainty in pharmacokinetic efficacy and LAI-PrEP persistence relative to DO-PrEP. Results: Compared to the reference scenario, if 50% chose LAI-PrEP, 4.3% (95% SI: −7.3%, 14.5%) of infections would be averted over 10 years. LAI-PrEP impact is slightly greater than the DO-PrEP only regimen based on assumptions of higher adherence and partial protection after discontinuation. If the total PrEP initiation rate doubled, 17.1% (95% SI: 6.7%, 26.4%) of infections would be averted. The highest population-level impact occurred when LAI-PrEP uptake and persistence improved. Conclusions: If LAI-PrEP replaces DO-PrEP, its availability will modestly improve the population impact. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage, or if persistence is greater for LAI-PrEP. Summary: Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) will modestly decrease HIV incidence if it replaces daily-oral PrEP use among men who have sex with men. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage.