Pre-exposure Prophylaxis Regimens Research Articles

Interventions to Improve Adherence to Oral Pre-exposure Prophylaxis: A Systematic Review and Network Meta-analysis.

For people at risk of HIV infection, pre-exposure prophylaxis (PrEP) can reduce the risk of infection in anticipation of exposure to HIV. The effectiveness of PrEP relies upon a user's adherence to their PrEP regimen. We sought to assess the effect of PrEP adherence interventions compared to usual care or another intervention for people at risk of HIV. We searched electronic databases from 2010 onwards for randomized controlled trials (RCTs) involving persons at risk of HIV randomized to an adherence promoting intervention vs usual care or another intervention. We used network meta-analyses to compare PrEP adherence for all participant populations. Certainty of evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). 21 trials (N = 4917) were included in qualitative analysis (19 in network meta-analyses (N = 4101)). HIV self-testing interventions with adherence feedback elements improved adherence compared to usual care (risk ratio (RR): 1.83, 95%CI 1.19, 2.82). In contrast, HIV self-testing alone was inferior to HIV self-testing with adherence feedback (RR: 0.58, 95%CI 0.37-0.92). Reminders alone also were inferior to HIV self-testing with adherence feedback on adherence (RR: 0.53, 95%CI 0.34-0.84) and had similar effects on adherence as usual care (RR: 0.98, 95%CI: 0.86-1.11). Interventions with only one component were inferior for adherence than those with two components (RR: 0.74, 95%CI 0.62-0.88) and those with three components (RR: 0.78, 95%CI 0.65-0.93). The certainty of evidence was moderate for HIV self-testing plus adherence feedback and interventions with two or three components. When designing future PrEP adherence interventions, we recommend strategies with more than one but no more than three components.

Evaluating Dual Process Decision-Making Along the PrEP Consumer Journey: New Insights for Supporting PrEP Use.

With the rise of new and emerging Pre-Exposure Prophylaxis (PrEP) modalities, greater attention is needed to better understand how people who could benefit from PrEP make decisions to initiate, stop, pause, or switch PrEP regimens. In this study we borrow from the field of consumer research to create a consumer-derived PrEP Consumer Journey Model that describes key decision-making touchpoints a PrEP consumer moves through within and outside of a clinical context. Using in-depth interviews (n = 29) with gay and bisexual men who have sex with men, we evaluate which system 1 (emotional) and system 2 (cognitive) attributes are used for decision-making at different touchpoints along the PrEP Consumer Journey. Our results suggest system 1 attributes, such as feeling protected, reducing anxiety, enhancing pleasure, social norms, and taking ownership over health were more salient when consumers moved from pre-contemplation to information gathering, as well as evaluating post-uptake experience. System 2 attributes, including cost, side effects, dosing schedule, and sexual frequency, were present throughout the PrEP Consumer Journey, but particularly influential in the information gathering stage and when pausing, switching, or opting out of PrEP. We contend the PrEP Consumer Journey, and our findings related to decision-making, can help orient medical providers to anticipated patient concerns around PrEP use and ultimately provide more supportive and engaging PrEP counseling and services.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP—to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation—to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Sexual behaviour and incidence of sexually transmitted infections among men who have sex with men (MSM) using daily and event-driven pre-exposure prophylaxis (PrEP): Four-year follow-up of the Amsterdam PrEP (AMPrEP) demonstration project cohort.

An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP. The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals. In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time. The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.

Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.

Pre-exposure prophylaxis (PrEP) with a weekly oral regimen of antiretroviral drugs could be a suitable preventative option for individuals who struggle with daily PrEP or prefer not to use long-acting injectables. We assessed in macaques the efficacy of weekly oral tenofovir alafenamide (TAF) at doses of 13.7 or 27.4 mg/kg. Macaques received weekly oral TAF for six weeks and were exposed twice-weekly to SHIV vaginally or rectally on day 3 and 6 after each dose. Median TFV-DP levels in PBMCs following the 13.7 mg/kg dose were 3110 and 1137 fmols/106 cells on day 3 and 6, respectively. With the 27.4 mg/kg dose, TFV-DP levels were increased (~2-fold) on day 3 and 6 (6095 and 3290 fmols/106 cells, respectively). Both TAF doses (13.7 and 27.4 mg/kg) conferred high efficacy (94.1% and 93.9%, respectively) against vaginal SHIV infection. Efficacy of the 27.4 mg/kg dose against rectal SHIV infection was 80.7%. We estimate that macaque doses of 13.7 and 27.4 mg/kg are equivalent to approximately 230 and 450 mg of TAF in humans, respectively. Our findings demonstrate the effectiveness of a weekly oral PrEP regimen and suggest that a clinically achievable oral TAF dose could be a promising option for non-daily PrEP.

“AIDSImpact Special Issue” – High PrEP acceptability and need for tailored implementation in Cambodian key populations: results from a qualitative assessment

ABSTRACT The HIV epidemics in Cambodia is concentrated in key populations (KPs). Pre-exposure prophylaxis (PrEP) has been officially approved in the country since 2019. However, its use may still be controversial after a PrEP clinical trial was interrupted in Cambodia after being deemed unethical in 2004. In this context, it was necessary to evaluate PrEP acceptability and administration preferences of KPs in Cambodia, with a view to increasing roll-out and uptake. We conducted a qualitative study in 2022 comprising six focus groups and four semi-structured individual interviews with transgender women, men who have sex with men, male entertainment workers, venue-based female entertainment workers (FEW), street-based FEW, and PrEP users who participated in a PrEP pilot study that started in 2019. Overall, KPs positively perceived PrEP, with some reservations. They preferred daily, community-based PrEP to event-driven, hospital-based PrEP, and highlighted that injectable PrEP would be a potential option if it became available in Cambodia. We recommend (i) proposing different PrEP regimens and PrEP delivery-models to broaden PrEP acceptability and adherence in Cambodia (ii) increasing the number of community-based organisations and improving the services they offer, (iii) rolling out injectable PrEP when it becomes officially available, and (iv) improving PrEP side effects information.

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.

Lived experiences with pre-exposure prophylaxis uptake and adherence among transgender women in Thailand: a qualitative study.

Transgender women (TGW) are disproportionately affected by HIV, and HIV prevalence among TGW in Thailand has been increasing. Although oral daily pre-exposure prophylaxis (PrEP) is effective for HIV prevention, PrEP uptake and persistence among TGW have been low. This study aimed to provide a deeper understanding of TGW's experiences with PrEP uptake and adherence, and to identify major barriers to PrEP use to inform intervention adaptation. We interviewed 20 young TGW (six non-PrEP users, eight adherent, six non-adherent) and 10 health care providers from two HIV clinics in Bangkok, Thailand, in 2022. We focused on understanding challenges to PrEP use in this population using an interview guide based on a theoretical model of behaviour change and thematic content analysis. Thematic analysis identified major barriers to and facilitators of PrEP uptake and adherence. Barriers to PrEP initiation included low self-perceived HIV risk, concern about potential side-effects, patient burdens such as frequent HIV testing for prescription refills and social stigma against PrEP. Barriers to adherence included side-effects, inconvenient access to health services (especially during COVID-19 lockdowns), forgetfulness resulting from busy schedules and low self-perceived HIV risk. TGW also reported health care providers' stigma against PrEP users deterred them from seeking further PrEP services. TGW identified major facilitators of PrEP initiation, including awareness about the benefits of PrEP, concern about risks of HIV and supportive social networks of PrEP users. As to PrEP regimens, most TGW participants reported a clear preference for long-lasting, injectable PrEP over daily oral PrEP. TGW and health care providers largely agreed on barriers and facilitators of PrEP use, but they differed in perceptions of HIV risk. The results highlighted challenges and opportunities to improve the delivery of PrEP, as well as other sexually transmissable infection and mental health services, especially among TGW. Thus, there is an urgent need for developing effective intervention programs that could raise PrEP awareness and knowledge, reduce PrEP stigma, and improve PrEP delivery systems among TGW in Thailand.

Machine learning and pre-exposure prophylaxis: A survey

The goal of this paper was to study how machine learning techniques have been applied in PrEP (Pre-exposure prophylaxis) and HIV prediction to identify individuals who are at a higher risk of acquiring HIV infection and to optimize the used of PrEP, which is an effective method of preventing HIV transmission. The results indicate that machine learning has been used to HIV risk, optimizing PrEP use, developing personalized PrEP regimens, and identifying PrEP candidates. In predicting HIV risk, machine learning algorithms have been developed to predict HIV risk based on various factors such as demographic information, sexual behavior and drug use. The models can identify individuals who are at a higher risk of acquiring HIV infection and can be used to target interventions such as PrEP to those who are most in need. Regarding optimizing PrEP use, machine learning has been utilized to optimize PrEP usage by identifying the factors that are associated with adherence to PrEP. These models can help healthcare providers to tailor their interventions to promote PrEP adherence and improve its effectiveness. In addition, machine learning techniques have been used to develop personalized PrEP regimens based on an individual’s HIV risk profile. These models can help healthcare providers to optimize PrEP use and reduce the risk of HIV transmission. It was also established that machine learning models have been used to identify individuals who are most likely to benefit from PrEP. These models can help healthcare providers to target PrEP interventions to those who are likely to benefit from them.

Dynamics of a two-group model for assessing the impacts of pre-exposure prophylaxis, testing and risk behaviour change on the spread and control of HIV/AIDS in an MSM population

Although much progress has been made in reducing the public health burden of the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), since its emergence in the 1980s (largely due to the large-scale use and availability of potent antiviral therapy, improved diagnostic and intervention and mitigation measures), HIV remains an important public health challenge globally, including in the United States. This study is based on the use of mathematical modeling approaches to assess the population-level impact of pre-exposure prophylaxis (PrEP), voluntary testing (to detect undetected HIV-infected individuals), and changes in human behavior (with respect to risk structure), on the spread and control of HIV/AIDS in an MSM (men-who-have sex-with-men) population. Specifically, a novel two-group mathematical model, which stratifies the total MSM population based on risk (low or high) of acquisition of HIV infection, is formulated. The model undergoes a PrEP-induced backward bifurcation when the control reproduction number of the model is less than one if the efficacy of PrEP to prevent a high-risk susceptible MSM individual from acquiring HIV infection is not perfect (the consequence of which is that, while necessary, having the reproduction number of the model less than one is no longer sufficient for the elimination of the disease in the MSM population). For the case where the efficacy of PrEP is perfect, this study shows that the disease-free equilibrium of the two-group model is globally-asymptotically stable when the associated control reproduction number of the model is less than one. Global sensitivity analysis was carried out to identify the main parameters of the model that have the highest influence on the value of the control reproduction number of the model (thereby, having the highest influence on the disease burden in the MSM population). Numerical simulations of the model, using a plausible range of parameter values, show that if half of the MSM population considered adhere strictly to the specified PrEP regimen (while other interventions are maintained at their baseline values), a reduction of about 22% of the new yearly HIV cases recorded at the peak of the disease could be averted (compared to the worst-case scenario where PrEP-based intervention is not implemented in the MSM population). The yearly reduction at the peak increases to about 50% if the PrEP coverage in the MSM population increases to 80%. This study showed, based on the parameter values used in the simulations, that the prospects of elimination of HIV/AIDS in the MSM community are promising if high-risk susceptible individuals are no more than 15% more likely to acquire HIV infection, in comparison to their low-risk counterparts. Furthermore, these prospects are significantly improved if undetected HIV-infected individuals are detected within an optimal period of time.

Uptake of Oral HIV Pre-Exposure Prophylaxis (PrEP) and Associated Factors among Female Sex Workers in Tanga, Tanzania.

Pre-exposure prophylaxis (PrEP) prevents HIV infection among female sex workers (FSW). WHO recommends the use of Tenofovir disoproxil fumarate for use in oral PrEP regimens (TDF). Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil Fumarate (TDF) 300 mg (Truvada) daily is the approved PrEP regimen in Tanzania. Evidence is limited on oral PrEP uptake and its associated factors in countries with a high burden of HIV, such as Tanzania. This study aimed to examine the uptake of oral PrEP and its associated factors among FSW in the Tanga region of Tanzania. This community-based cross-sectional study was conducted among 428 FSW. Data were collected through face-to-face interviews and analysed using STATA version 17 and RDSAT. Logistic regression was used to examine the associations of independent factors and PrEP uptake among study participants. About 55% of the recruited FSW used oral PrEP. FSW with three or more children were 2.41 times more likely to take oral PrEP (AOR 2.41, 95% CI: 1.08-4.25, p < 0.05). Moreover, those with a positive attitude were more likely to use oral PrEP (AOR 2.8, 95% CI: 1.88-4.17, p < 0.05). Poor belief was a barrier to PrEP use, and side effects of the drugs were a reason for the discontinuation of PrEP services. Most of the participants preferred PrEP services to be provided in the community. Oral PrEP uptake was 55%. Efforts to scale up PrEP for FSW should address misconceptions regarding PrEP, PrEP sensitization, and improving access through community-based intervention.

A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention.

A priori use of mathematical modeling and simulation to predict outcomes from incomplete adherence or reduced frequency dosing strategies may mitigate the risk of clinical trial failure with HIV pre-exposure prophylaxis regimens. We developed a semi-physiologic population pharmacokinetic model for two antiretrovirals and their active intracellular metabolites in three mucosal tissues using pharmacokinetic data from a phase I, dose-ranging study. Healthy female volunteers were given a single oral dose of tenofovir disoproxil fumarate (150, 300, or 600 mg) or emtricitabine (100, 200, or 400 mg). Simultaneous co-modeling of all data was performed on a Linux cluster. A 16 compartment, bolus input, linear kinetic model best described the data, containing 986 observations in 23 individuals across three matrices and four analytes. Combined with a defined efficacious concentration target in mucosal tissues, this model can be used to optimize the dose and dosing frequency through Monte-Carlo simulations.

Preferences for long-acting pre-exposure prophylaxis among gay, bisexual and other men who have sex with men in Taiwan: findings from the 2021 HEART Survey.

While various antiretrovirals have been studied as potential candidates for long-acting pre-exposure prophylaxis (PrEP), the bimonthly injectable cabotegravir-the first long-acting form of PrEP-was approved in 2021. Event-driven (ED) PrEP has been the most prevalent dosing regimen among gay, bisexual and other men who have sex with men (GBMSM) in Taiwan, providing a unique setting to observe the preferences for long-acting PrEP in a community where the daily regimen is not the mainstream method. This study aimed to determine the preferences for the different forms and dosing intervals of long-acting PrEP that are currently in the development pipeline. We conducted a survey in 2021 by convenience sampling the users of social networking applications for GBMSM in Taiwan. Our survey included questions on sexual behaviours, current PrEP regimens and the preferences for potential candidates of long-acting PrEP, such as implants, intramuscular and subcutaneous injections. We compared the Likert-scale preference ratings for potential long-acting options, and conducted logistic regression analysis to examine the factors associated with a preference for bimonthly intramuscular injections (2M IM) over ED and daily PrEP regimens, respectively. A total of 1728 responses were eligible for analysis. Three percent of respondents (n = 52) were daily PrEP users; 11.5% (n = 198) were ED PrEP users. When not considering cost, current PrEP users-regardless of their original dosing regimen-were most likely to express preferences for monthly oral PrEP, followed by a 6-month subcutaneous injectable (6M SC) and 2M IM. However, among non-current PrEP users, monthly oral PrEP was the most preferred form, followed by ED, daily oral and 6M SC injectable. Multivariable logistic regression revealed that current daily users, those willing to take PrEP in the next 6 months and those with more sex partners in the last 12 months had a significant correlation with preferences for the 2M IM injectable over the ED PrEP. The monthly oral form was the most preferable long-acting PrEP among GBMSM in Taiwan. Current daily PrEP users preferred the 2M IM injectable over the ED PrEP, which made the 2M IM injectable a potential alternative. Further studies should focus on how the cost and delivery affect PrEP preferences and their actual uptake.

Long-acting lenacapavir protects macaques against intravenous challenge with simian-tropic HIV

Long-acting subcutaneous lenacapavir (LEN), a first-in-class HIV capsid inhibitor approved by the US FDA for the treatment of multidrug-resistant HIV-1 with twice yearly dosing, is under investigation for HIV-1 pre-exposure prophylaxis (PrEP). We previously derived a simian-tropic HIV-1 clone (stHIV-A19) that encodes an HIV-1 capsid and replicates to high titres in pigtail macaques (PTM), resulting in a nonhuman primate model well-suited for evaluating LEN PrEP invivo. Lenacapavir potency against stHIV-A19 in PTM peripheral blood mononuclear cells invitro was determined and subcutaneous LEN pharmacokinetics were evaluated in naïve PTMs invivo. To evaluate the protective efficacy of LEN PrEP, naïve PTMs received either a single subcutaneous injection of LEN (25mg/kg, N=3) or vehicle (N=4) 30 days before a high-dose intravenous challenge with stHIV-A19, or 7 daily subcutaneous injections of a 3-drug control PrEP regimen starting 3 days before stHIV-A19 challenge (N=3). Invitro, LEN showed potent antiviral activity against stHIV-A19, comparable to its potency against HIV-1. Invivo, subcutaneous LEN displayed sustained plasma drug exposures in PTMs. Following stHIV-A19 challenge, while all vehicle control animals became productively infected, all LEN and 3-drug control PrEP animals were protected from infection. These findings highlight the utility of the stHIV-A19/PTM model and support the clinical development of long-acting LEN for PrEP in humans. Gilead Sciences as part of a Cooperative Research and Development Agreement between Gilead Sciences and Frederick National Lab; federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024/HHSN261201500003I; NIH grant R01AI078788.

Trajectories of PrEP use among men who have sex with men: a pooled analysis of two prospective, observational cohort studies.

Daily and event-driven oral pre-exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use irrespective of the chosen PrEP regimens among men who have sex with men (MSM). Using data from a mobile, web-based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be-PrEP-ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event-driven oral PrEP every 3 months. We used group-based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories. We included 516 MSM (n = 322 AMPrEP; n = 194 Be-PrEP-ared), of whom 24% chose event-driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow-up (median = 508 days [IQR = 429-511]). Four distinct PrEP use trajectories were identified: ≤2 tablets per week ("low frequency," 12% of the total population), 4 tablets per week ("variable," 17%), "almost daily" (31%) and "always daily" (41%). Compared to participants with "low frequency" PrEP use, participants with "variable" (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.04-4.60) and "almost daily" PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27-5.49). "Almost daily" PrEP users were more often employed (OR = 6.76, 95% CI = 2.10-21.75) and were younger compared to participants with "low frequency" PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with "low frequency" PrEP use compared to the other groups (all p<0.001). Compared to "low frequency" PrEP users, the incidence rates of chlamydia and gonorrhoea were higher for participants with "almost daily" and "always daily" PrEP use. We uncovered four distinct PrEP use trajectories, pointing to different patterns of PrEP use in practice beyond the two-regimen dichotomy. These trajectories were related to sexual behaviour and rates of sexually transmitted infection. Tailoring PrEP care according to different PrEP use patterns could be an important strategy to improve efficient PrEP delivery.

Mass spectrometry imaging of hair identifies daily maraviroc adherence in HPTN 069/ACTG A5305.

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study's active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes.

Personalizing prevention: Advances in pharmacotherapy for HIV prevention.

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence.

Exploring preferences and decision-making about long-acting injectable HIV pre-exposure prophylaxis (PrEP) among young sexual minority men 17–24 years old

Intramuscular cabotegravir for long-acting injectable HIV pre-exposure prophylaxis (i.e., LAI-PrEP) was approved by the U.S. FDA in 2021. We sought to explore LAI-PrEP decision-making among a nationwide sample of young sexual minority men (YSMM) 17–24 years old. In 2020, HIV-negative/unknown YSMM (n = 41) who met CDC criteria for PrEP were recruited online to participate in synchronous online focus groups eliciting preferences and opinions about LAI-PrEP, as well as the impact of a potential self-administered option. Data were analyzed using inductive and deductive thematic analysis with constant comparison. Preferences and decision-making about LAI-PrEP varied widely among YSMM, with participants frequently comparing LAI-PrEP to oral PrEP regimens. We identified five key themes related to LAI-PrEP decision-making including concerns about adherence to PrEP dosing and clinic appointments, awareness and knowledge of PrEP safety and efficacy data, comfort with needles, minimizing PrEP stigma, and considerations of self-administration. YSMM acknowledged more PrEP options as beneficial to supporting uptake and persistence.

Provider Implicit Bias in Prescribing HIV Pre-exposure Prophylaxis (PrEP) to People Who Inject Drugs

BackgroundMultiple HIV outbreaks among people who inject drugs (PWIDs) have occurred in the USA since 2015, highlighting the need for additional HIV prevention tools. Despite high levels of need, pre-exposure prophylaxis (PrEP) is drastically underutilized among PWIDs. Implicit bias toward PWID held by clinicians may impede PrEP scale-up among these underserved patients. This study examined how primary care providers’ (PCPs) clinical decisions related to PrEP can be impacted by biases when the patient has a history of substance use.MethodsWe conducted an online survey of PCPs (n = 208). The survey included the implicit association test (IAT) to assess unconscious attitudes toward PWIDs, direct questions regarding clinicians’ explicit PWID attitudes, and an embedded experiment in which we systematically varied the risk behavior of a hypothetical patient and asked PCPs to make clinical judgments.ResultsA minority (32%) of PCPs reported explicit PWID bias. The IAT indicated strong implicit PWID bias (meant IAT score = 0.59, p < .0001) among 88% of the sample. Only 9% of PCPs had no implicit or explicit PWID bias. PWID patients were judged as less likely to adhere to a PrEP regimen, less responsible, and less HIV safety conscious than heterosexual or gay male patients. Anticipated lack of adherence mediated PCPs’ intent to prescribe PrEP to PWID.ConclusionsPCPs’ bias may contribute to PrEP being under-prescribed to PWID. Implicit and explicit PWID biases were common in our sample. This study illustrates the need to develop and test tailored interventions to decrease biases against PWID in primary care settings.

Cost analysis of implementation of a population level rabies control programme for children in India

BackgroundRabies is an endemic and major public health problem in India. This paper reports cost of implementation of various Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) strategies at programmatic level to avert rabies deaths in children in India. MethodsThe cost of implementation of various PrEP + PEP and PEP only regimens recommended by WHO and national guidelines was calculated separately for the first year of implementation for children in the age group of 0–5 years (U-5) and 5–15 years (U-15). The cost was calculated at the level of health facility from government's perspective considering the implementation of the strategies under National Rabies Control Program. All costs were converted into 2020 Indian National Rupee and International Dollars' value using implicit price deflators for Purchasing Power Parities. Base case, scenario and one-way sensitivity analyses were conducted. ResultsThe cost of implementation of PrEP regimen is several times higher than all other PEP regimens in children in the age groups of 0–5 years and 5–15 years for the first year of implementation. However, the study also reported use of intradermal route of vaccination and local infiltration of ERIG in wounds only as a cost-saving approach to prevent rabies deaths in children in situations where PEP only strategies are implemented. ConclusionsThere is a need to conduct primary studies in order to obtain data for cost of implementation of shorter regimens in real-time settings.