Pre-exposure Prophylaxis Administration Research Articles

Real World Use of Tixagevimab/Cilgavimab Pre-Exposure Prophylaxis of COVID-19 in Immunocompromised Individuals: Data from the OCTOPUS Study

Objective. We aimed to report the real-world use and outcomes over time in immunocompromised individuals receiving tixagevimab/cilgavimab (T/C) pre-exposure prophylaxis (PrEP). Methods. This observational study included participants who received T/C PrEP, categorized into three groups: (i) No COVID-19 (NoC), i.e., participants who never had COVID-19; (ii) Hybrids (H), i.e., participants who had COVID-19 before PrEP; and (iii) Break-through Infections (BTIs), i.e., participants who had COVID-19 after PrEP. The study measured several immune markers at the administration of T/C (T0) at 3 (T1), 6 (T2), and 9 (T3) months afterward. These markers included: anti-receptor-binding domain (RBD) IgG antibodies; BA.5-neutralizing antibodies (nAbs); mucosal IgG; and T cell immunity. The incidence rate ratios for BTIs were analyzed using a Poisson regression model. Results. A total of 231 participants with a median age of 63 years (IQR 54.0–73.0). were included. Among these, 84% had hematological diseases and received a median of three vaccine doses. N = 72 participants belonged to the NoC group, N = 103 to the H group, and n = 56 to the BTI group (24%), with most BTIs being mild/moderate. The incidence rate (IR) of BTIs was 4.2 per 100 patient-months (95% CI 3.2–5.4), with no associated risk factors identified. There was a significant increase in anti-RBD IgG levels 3 months after the T/C administration in all groups, followed by a decline at 6 months, whereas at the same time points, geometric mean titers (GMTs) of anti-BA.5 nAbs were low for all groups and were around or below the detection threshold. No significant changes were observed in IFN-γ levels. The mucosal immune response was observed only 3 months after the PrEP administration. Conclusion. We provided a real-world experience model on the clinical efficacy of T/C PrEP in preventing severe COVID-19 during the Omicron wave through a comprehensive virological and immunological study. While waiting for the arrival of new monoclonal antibodies that can effectively neutralize the most recent variants, T/C PrEP remains the only viable strategy in the available armamentarium today to prevent COVID-19 complications in an extremely fragile population with suboptimal immune responses to COVID-19 vaccines.

A Qualitative Exploration of PrEP Interests, Barriers, and Interventions Among Black and Latina Cisgender Women in the U.S.

Black and Latina cisgender women (BLCW) are disproportionally affected by HIV, particularly in the southern U.S. In Austin, Texas, Black women contract HIV 18.4 times more and Latinas 2.6 times more compared to White women. Pre-exposure prophylaxis (PrEP) is a medication that prevents contracting HIV; however, PrEP adoption among women is low. The current qualitative study aimed to explore PrEP awareness, interest, preferred PrEP administration methods, barriers to PrEP adoption, and future programs to increase PrEP adoption and adherence among BLCW. A total of 18 BLCW at high risk for HIV were enrolled. Participants completed 3 semi-structured interviews across 3 months. Interviews were transcribed verbatim, coded, and analyzed using thematic content analysis. Results demonstrated that BLCW had low PrEP awareness, high initial PrEP interest, and were interested in a long-acting injectable form of PrEP. Barriers to PrEP adoption included concerns regarding side effects, concerns about adherence to the currently available daily pill, and difficulty with insurance. Participants proposed different ideas for interventions, including support groups, education, community-level programs, and structural interventions. Future studies should focus on increasing PrEP awareness and HIV risk, consider alternative forms of PrEP, educate providers and medical staff on PrEP, and consider tailored interventions to reduce HIV risk among BLCW.

HIV pre-exposure prophylaxis and incidence of sexually transmitted infections in Brazil, 2018 to 2022: An ecological study of PrEP administration, syphilis, and socioeconomic indicators.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is one of the pillars of a combination prevention strategy for reducing the risk of new infections caused by HIV. The daily use of antiretroviral drugs by individuals who are not infected with HIV is required to prevent infection. Although its efficacy has been well established in the literature, in recent years, the decreased supply of antiretroviral drugs has been associated with an increase in the incidence of sexually transmitted infections (STI) and changes in the social determinants of health. An ecological study was conducted covering a five-year period (2018-2022), starting from the year of initiation of PrEP administration in Brazilian state capitals. Descriptive analysis was performed, and the spatial distribution of study data was taken into account. Correlation analysis was used to assess the association between PrEP administration, the incidence and detection rate of STI, and socioeconomic data. The southern region showed the highest incidence rates of STI, but the northern and northeastern regions demonstrated the worst socioeconomic indicators, especially those related to illiteracy and basic sanitation. PrEP administration was significantly correlated with illiteracy (ρ = -0.658), per capita income (ρ = 0.622), public garbage collection (ρ = 0.612), syphilis (ρ = 0.628) and viral hepatitis (ρ = 0.419) incidences. Further, all STI were significantly associated with illiteracy and per capita income. Our findings highlight the need to continue exploring PrEP use and rising syphilis rates. In terms of policy, PrEP administration appears to be inversely associated with regions of greater social vulnerability. Further efforts should focus on the social determinants and health needs of this population to improve access to PrEP and reduce social disparities.

A Comparison of Tenofovir Predose Concentrations in Generic Pre-exposure Prophylaxis Formulations: A Short Communication.

There is extensive evidence to show that pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate (TDF)-based formulations dramatically reduces the risk of HIV acquisition among individuals without HIV infection. Here, the authors aim to compare tenofovir plasma predose concentrations in subjects taking PrEP daily versus on demand and using different TDF-based generic formulations. Subjects providing informed signed consent for the measurement of tenofovir plasma levels were included in the study. Predose drug concentrations were stratified according to PrEP administration and the type of TDF-based formulation. The control group consisted of patients with HIV infection who were matched for renal function and were administered branded TDF that was not combined with boosted-antiretroviral drugs. The study consisted of 100 subjects (mean age, 39 ± 10 years; body weight, 77 ± 11 kg). A wide distribution in tenofovir predose concentrations was observed, with values ranging from 17 to 297 ng/mL (coefficient of variation 77%). No significant differences were noted in tenofovir predose concentrations between subjects who were administered PrEP daily (n = 75) or on demand (n = 25) [94 (35-255) versus 104 (37-287) ng/mL; P = 0.476]. Comparable tenofovir predose concentrations were found between patients with HIV infection (n = 220) who were administered branded TDF and those without HIV infection who were treated with 5 different generic TDF-based formulations with generics-to-branded ratios. These were always within the range of 80%-125% and were used to define bioequivalence. The marketed generic formulations of TDF delivered tenofovir plasma predose concentrations comparable with those delivered by branded formulations.

Underutilization of Pre-Exposure Prophylaxis Services Among Transgender and Nonbinary Youth: Findings from Project Moxie and TechStep.

We use quantitative and qualitative data from two ongoing studies to describe pre-exposure prophylaxis (PrEP) awareness, willingness to use PrEP, barriers to facilitators of PrEP uptake, and PrEP use among 15- to 24-year-old transgender and gender nonbinary (TGNB) youth. Most youth were aware of PrEP, but only one participant across both studies reported current use. Uncertainty about willingness to take PrEP may be related to general (e.g., medication cost) and trans-specific (e.g., PrEP–hormone interactions) concerns. Intensified and sustained efforts are needed to engage TGNB youth along the PrEP continuum and the impact of new PrEP administration and dosing options should be examined for TGNB youth.

An Ethical Claim for Administration of Pre-Exposure Prophylaxis (PREP) in HIV and AIDS Burdened Africa

It is morally justifiable for every person of good will to venture into HIV and AIDs prevention among the populace. Pre-exposure Prophylaxis (PrEP) administration promises to help meet the promise of this moral claim, which is founded on two ethical principles of ensuring wellbeing and justice for all. In spite of the efforts, challenges abound, especially in Africa. Some African tenets of sexuality, unavailability of contextualized and harmonized African sexuality theory as well as Africa’s poor economic standing are major threats to the administration of PrEP. This paper highlighted the major challenges and calls for their resolution if PrEP administration is to be of help to the poor and HIV burdened Africans.Key Words: HIV prevention, Preexposure Prophylaxis (PrEP), well-being, justice

Optimizing access to PrEP based on MSM preferences: results of a discrete choice experiment

ABSTRACTIntroduction: Despite documented effectiveness of pre-exposure prophylaxis (PrEP), PrEP uptake remains low among men who have sex with men (MSM), the population bearing the highest HIV burden in the U.S. Objectives: To elicit MSM stakeholder preferences in order to inform program development aimed at improving uptake of PrEP. METHODS: 554 MSM were recruited through social networking applications to complete a stated preference [choice-based conjoint (CBC)] survey. Respondents completed 14 choice tasks presenting experimentally varied combinations of five attributes related to PrEP administration (dosing frequency, dispensing venue, prescription practices, adherence support, and costs). Latent class analysis was used to estimate the relative importance of each attribute and preferences across seven possible PrEP delivery programs. Results: Preferences clustered into five groups. PrEP affordability was the most influential attribute across groups, followed by dosing strategy. Only one group liked daily and on-demand PrEP equally (n = 74) while the other four groups disliked the on-demand intermittent option. Monthly injectable PrEP is preferred by two (n = 210) out of the five groups, including young MSM. Two groups (n = 267) were willing to take PrEP across all the hypothetical programs. One group (n = 183) almost exclusively considered costs in their decision-making. Participants in the most racially diverse among groups (n = 88) had a very low level of interest in PrEP initiation. Conclusion: Our data suggest that PrEP uptake will be maximized by making daily PrEP affordable to MSM and streamlining PrEP consultation visits for young MSM. Young MSM should be prioritized for injectable PrEP when it becomes available. A successful PrEP program will spend resources on removing structural barriers to PrEP access and educating MSM of color, and will emphasize protection of privacy to maximize uptake among rural/suburban MSM.

Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis

Pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) drugs are effective at preventing human immunodeficiency virus (HIV) transmission. However, implementation of PrEP presents significant challenges due to poor user adherence, low accessibility to ARVs and multiple routes of HIV exposure. To address these challenges, we developed the nanochannel delivery implant (NDI), a subcutaneously implantable device for sustained and constant delivery of tenofovir alafenamide (TAF) and emtricitabine (FTC) for HIV PrEP. Unlike existing drug delivery platforms with finite depots, the NDI incorporates ports allowing for transcutaneous refilling upon drug exhaustion. NDI-mediated drug delivery in rhesus macaques resulted in sustained release of both TAF and FTC for 83 days, as indicated by concentrations of TAF, FTC and their respectively metabolites in plasma, PBMCs, rectal mononuclear cells and tissues associated with HIV transmission. Notably, clinically relevant preventative levels of tenofovir diphosphate were achieved as early as 3 days after NDI implantation. We also demonstrated the feasibility of transcutaneous drug refilling to extend the duration of PrEP drug delivery in NHPs. Overall, the NDI represents an innovative strategy for long-term HIV PrEP administration in both developed and developing countries.

Strategies to Implement Pre-exposure Prophylaxis with Men Who Have Sex with Men in Ukraine.

Ukrainian men who have sex with men (MSM) remain highly stigmatized group with HIV prevalence as high as 23%. Despite documented effectiveness of pre-exposure prophylaxis (PrEP), PrEP remains unavailable in Ukraine. The aim of this study was to elicit MSM preferences in order to inform program development to facilitate successful delivery of PrEP to Ukrainian MSM. 1184 MSM were recruited through social networking applications to complete a stated preference (choice-based conjoint) survey. Respondents completed 14 choice tasks presenting experimentally-varied combinations of five attributes related to PrEP administration (dosing frequency, dispensing venue, prescription practices, adherence support, and costs). Latent class analysis was used to estimate the relative importance of each attribute and preferences across nine possible PrEP delivery programs. Preferences clustered into five groups. PrEP affordability was the most influential attribute across groups, followed by dosing strategy. Only one group preferred injectable PrEP (n=216), while the other four groups disliked daily PrEP and strongly preferred the 'on demand' option. One group (n=258) almost exclusively considered cost in their decision making. One group (n=151) had very low level of interest in PrEP initiation correlated with low self-perceived risk for HIV. The two most at-risk groups (n=415) were also more sensitive to changes in program delivery. PrEP uptake among MSM is most likely to be successful when PrEP is affordable, its implementation is targeted, provided as "on-demand" with associated education, and when more thorough medical care and related testing is provided to at-risk populations. Its introduction will need affirmation by the Ukrainian government, and guidelines that reflect safety, efficacy, and patient preferences.

Summary of Guidelines for the Use of Pre-Exposure Prophylaxis for HIV in Korea.

There are several guidelines for the use of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) which are used in other countries. However, the implementation of such guidelines in each country should be modified according to the country's clinical and epidemiological situation. Therefore, The Korean Society for AIDS founded a committee in 2016 to develop guidelines for the use of PrEP for HIV that are optimal for Korea's clinical and epidemiological situation. These guidelines aim to provide comprehensive information for PrEP implementation in Korea. The recommendations contain important information for physicians working to prevent HIV infection in actual clinical fields. The committee will regularly review and revise the guidelines based on changes in PrEP administration and HIV prevention practices.

Beyond "getting drugs into bodies": social science perspectives on pre-exposure prophylaxis for HIV.

Social scientists have much to contribute to the analysis of the real and potential contribution of pre-exposure prophylaxis (PrEP) to HIV prevention around the world. Beyond just a matter of clinical efficacy and getting pills into people's mouths, PrEP raises a number of important social-psychological questions that must be attended to in order to translate biomedical and clinical findings into uptake of PrEP among enough people at risk of HIV infection to produce population-level effectiveness. PrEP is a dynamic phenomenon with “dialectical” attributes that invite both optimism and cynicism as a desirable and effective HIV prevention strategy. PrEP disrupts traditional notions of “safe” and “unsafe” sex; it confers on its users a level of agency and control not generally achieved with condoms; and it affects sexual practices and sexual cultures in meaningful ways. As these dynamics play out in different contexts, and as new modes of PrEP administration emerge, it will be important for social scientists to be engaged in assessing their impact on PrEP implementation and effectiveness.