Abstract Cancer stemness properties, including enhanced survival, malignant regeneration, telomere deregulation, genomic and epitranscriptomic instability, fuel metastases, and have been linked to stress, retrotransposon and inflammatory cytokine activation, which can occur in low earth orbit (LEO). In NASA Axiom 1, 2 and 3 missions to the ISS, confocal imaging, WGS, RNA-seq and scRNA-seq of lentiviral FUCCI2BL cell cycle and ADAR1-GFP reporter transduced erythroleukemia (TF-1a), colorectal (Caco-2) and metastatic breast cancer (MBC; MDA-MB-231 and patient samples) revealed proliferation, significant genomic instability, HERV and LINE-1 retrotransposon deregulation, and APOBEC3C and ADAR1 activation. Moreover, in Axiom 2 and 3 missions with ADAR1-reporter expressing MBC organoids and in humanized MBC mouse models, an ADAR1p150 splicing modulator, rebecsinib (IND 153126), prevented tumor propagation. Thus, cancer studies in LEO may accelerate the development of innovative cancer therapeutics and countermeasures for long-term spaceflight. Citation Format: Jessica Pham, Wenxue Ma, Claire Engstrom, Patrick Chang, Shuvro P. Nandi, Inge van der Werf, Emma Klacking, Teresa Sposito, Kendale Wirtjes, Thomas Frias, Antonio Ruiz, Jane Isquith, Luisa Ladel, Christina N. Wu, Jana Stoudemire, Pinar Mesci, Kay T. Yeung, Rebecca A. Shatsky, Anna A. Khachatrian, James J. La Clair, Michael D. Burkart, Peggy Wentworth, Curtis L. Scribner, Sheldon R. Morris, Thomas Whisenant, Karla Mack, Ludmil B. Alexandrov, Catriona H. Jamieson. Predicting and preventing cancer stemness in low Earth orbit [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7631.

Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team developed bone marrow niche nanobioreactors with lentiviral bicistronic fluorescent, ubiquitination-based cell-cycle indicator (FUCCI2BL) reporter for real-time HSPC tracking in artificial intelligence (AI)-driven CubeLabs. In monthlong International Space Station (ISS) missions (SpX-24, SpX-25, SpX-26, and SpX-27) compared with ground controls, FUCCI2BL reporter, whole-genome and transcriptome sequencing, and cytokine arrays demonstrated cell-cycle, inflammatory cytokine, mitochondrial gene, human repetitive element, and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) deregulation together with clonal hematopoietic mutations. Furthermore, HSPC functionally organized multi-omics aging (HSPC-FOMA) analyses revealed reduced telomere maintenance, adenosine deaminase acting on RNA1 (ADAR1) p150 self-renewal gene expression, and replating capacity indicative of space-associated HSPC aging that may limit long-duration spaceflight.

Previous reports revealed immune dysfunction, chromosomal abnormalities, cytokine deregulation, and telomere alterations after prolonged spaceflight. However, the stress of space on hematopoietic stem and progenitor cells (HSPCs) and the resilience properties maintaining lifelong hematopoiesis and immunity were not studied. We performed HSPC functionally organized multi-omics aging and resilience (HSPC-FOMA-R) analyses in 9 astronauts before, during, and after three short-duration International Space Station (ISS) missions. Whole-genome sequencing (with telomere length analysis and mitochondrial and clonal mutational profiling), whole-transcriptome sequencing (with RNA editing and retrotransposon analyses), single-cell RNA sequencing, cytokine arrays, and fluorescence-activated cell sorting (FACS) analyses assessed HSPC and immune subpopulation survival dynamics. We show that spaceflight is associated with partially reversible changes in HSPC survival and self-renewal, adenosine deaminase associated with RNA1 (ADAR1), telomere maintenance, mobilization, cell cycle, and “fight or flight” gene expression. Combined with clonal hematopoietic mutations, apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3C) activation, and retrotransposon deregulation, HSPC-FOMA-R analyses are needed before extended missions.

Black and Latinx transgender women in the United States (U.S.) are at disproportionately high risk for HIV. Although HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection, uptake and persistence (i.e., ability to continue taking PrEP over time) can be a challenge for Black and Latinx transgender women due to myriad social and structural forces. In this qualitative study, we present unique data on the facilitators of PrEP persistence from Black and Latinx transgender women who initiated PrEP and exhibited varying levels of persistence during a demonstration project in Southern California. PrEP persistence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels on dried blood spot (DBS) samples collected at weeks 12 and 48. Informed by the socioecological framework, we conducted and analyzed interviews using qualitative content analysis to determine themes on the facilitators of PrEP persistence. Individual-level facilitators included the use of reminders, having high individual-level HIV risk perception, feeling empowered to take PrEP, and reporting having improved peace of mind and mental health because of taking PrEP. Interpersonal/Community-level facilitators included feeling motivation to prevent HIV in the community, motivation to prevent HIV in the context of sex work, and having high community-level risk perception. Structural-level facilitators included having positive experiences in affirming healthcare settings and having PrEP visits combined with other gender-related healthcare visits. Interventions aiming to increase PrEP uptake and persistence among Black and Latinx transgender women in the U.S. should harness the multiple levels of support exhibited by those who were able to start and persist on PrEP in the face of the myriad social and structural barriers.

Stem cell aging is accelerated by macroenvironmental and microenvironmental stressors, including inflammation. Previously, the NASA Twins study revealed inflammatory cytokine upregulation, chromosomal alterations, and telomere changes suggestive of accelerated aging in low-Earth orbit (LEO). To investigate the effects of spaceflight on human hematopoietic stem and progenitor cell (HSPC) aging, the NASA-supported Integrated Space Stem Cell Orbital Research team performed four independent 30- to 45-day NASA missions with matched flight and ground HSPC nanobioreactors in automated CubeLabs. These experiments revealed loss of HSPC dormancy, reduced self-renewal capacity, mitochondrial DNA amplification, APOBEC3-induced C-to-T mutagenesis, reduced ADAR1p150 expression, and alterations in the expression of repetitive elements. These molecular changes are indicative of accelerated HSPC aging and pre-leukemia stem cell generation in space and may be predictable and preventable. ### Competing Interest Statement C.H.M.J. co-founded Impact Biomedicines and is a co-founder of Aspera Biomedicines; received royalties from Forty Seven Inc. Other authors have no relevant competing interests.

BACKGROUND:Despite the rise in gender-affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) remains in its infancy. Health disparities and lack of PCa awareness and screening are possible barriers to providing quality care for this population. In addition, the implication of hormonal manipulation for the aggressiveness of PCa in TGW is yet to be determined. Here, this study sought to compare oncological characteristics and survival outcomes between transgender and cisgender (CG) patients with PCa via two national data sets. METHODS:The Veterans Affairs Informatics and Computing Infrastructure database (1999-2020) and the Surveillance, Epidemiology, and End Results-Medicare database (2010-2017) were reviewed. Demographic and clinical details were analyzed. Logistic regression analysis was performed on propensity score-matched groups to identify predictors of high-risk disease and metastasis in patients with PCa. Groups were matched 5:1 (CG:TGW) on the basis of age, race, year of diagnosis, and Charlson Comorbidity Index score. Primary outcomes included metastatic presentation, high-risk localized disease, overall survival (OS), and prostate cancer-specific mortality (PCSM). RESULTS:A total of 1194 patients were included (199 TGW; 995 CG). Associations between transgender identity and metastatic presentation (odds ratio [OR], 0.38; p = .2), high-risk localized disease (OR, 1.19; p = .50), or PCSM (hazard ratio [HR], 0.65; p = .3) were not detected. Transgender identity was associated with improved OS (HR, 0.67; p = .014). CONCLUSIONS:PCa-specific outcomes seem comparable between TGW and CG men, although the study was underpowered to detect modest differences. Further investigation into the incidence and outcomes of PCa in TGW is warranted.

Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in “non-survival sex work” had little difficulty staying on PrEP, while those engaged in “survival sex work” struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in “survival sex work” experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

Introduction Acute myeloid leukemia (AML) is characterized by a clonal proliferation of myeloid progenitors with a reduced capacity to differentiate into more mature cellular elements. Adenosine deaminase acting on RNA 1 (ADAR1) is an enzyme that is involved in the editing of messenger RNA (mRNA) transcripts (A-to-I RNA editing), which can alter the function of the resulting protein. ADAR1 drives cancer stem cell (CSC) generation and therapeutic resistance in many types of malignancies. As a potent small molecule splicing modulator, Rebecsinib inhibits splicing of ADAR1 into the ADAR1p150 isoform while Fedratinib inhibits JAK/STAT3 mediated activation of ADAR1p150 transcription1, 2. Methods To assess the relative ADAR1 inhibitory capacity of Rebecsinib and Fedratinib, humanized sAML mouse models were established with immunomagnetic bead-selected CD34+ cells from primary AML patient samples. Engrafted mice treated with Rebecsinib survived significantly longer compared to those treated with vehicle (p = 0.0003, log-rank test), Fedratinib (p = 0.016, log-rank test), and the combination of Rebecsinib and Fedratinib (p= 0.0002, log-rank test). In comparison, humanized aged normal bone marrow stem cell mouse models established by intravenous transplantation of CD34+ cells (obtained according to IRB-approved protocols from the bone marrow of patients undergoing hip replacement surgery), into NSG-SGM3 mice demonstrated increased human CD34+ cells engraftment in the bone marrow. Conclusions The results suggest that inhibition of ADAR1 splice isoform switching may provide a competitive advantage for normal hematopoietic stem cells compared with leukemia stem cells in the bone marrow niche and lay the foundation for developing clinical ADAR1p150 inhibitory strategies. References1. Crews L, Balaian L, Delos Santos, NP et al. RNA Splicing Modulation Selectively Impairs Leukemia Stem Cell Maintenance in Secondary Human AML. Cell Stem Cell. 2016; 19: 599-612, PMID: 275700672. Crews L, Ma W, Ladel L, et al. Reversal of Malignant ADAR1 Splice Isoform Switching with Rebecsinib. Cell Stem Cell. 2023.

Background: Little is known about the efficacy of preexposure prophylaxis (PrEP) or what biologic factors may influence HIV transmission in transgender men (TGM). In this study, we sought to explore the effect of testosterone on the vaginal microbiome, cervicovaginal fluid (CVF) tenofovir concentrations, and levels of CVF inflammatory markers in TGM on PrEP. Methods: Cervicovaginal fluid was collected from 13 TGM (7 using testosterone) and 32 cisgender women (CGW) on PrEP. The vaginal microbiome, CVF tenofovir concentrations, and CVF inflammatory markers were determined and compared. Results: The proportion of CVF Lactobacillus was significantly higher in CGW than in TGM (78% vs 24%, P < 0.001). Among TGM, the proportion of CVF Lactobacillus was lower, though not statistically significant, in those taking testosterone than in those not taking testosterone (14% vs 35%, P-value = 0.3). Interestingly, mean CVF tenofovir concentrations were the lowest in TGM on testosterone at 884 ng/mL compared with 3150 ng/mL in TGM not on testosterone and 1932 ng/mL in CGW; however, this difference was not statistically significant. There was no statistically significant difference in any of the genital inflammatory markers between groups and no correlation between inflammation and tenofovir levels. Conclusions: Our findings suggest a potential correlation between testosterone use, Lactobacillus dominance, and lower TFV concentrations in CVF, which may have implications on HIV acquisition from vaginal sex in TGMT. Future studies with larger sample sizes are needed to further investigate these relationships.

AimsMany transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT.MethodsThe study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took >= 12 weeks of TDF/FTC and then switched to >= 12 weeks of TAF/FTC for pre-exposure prophylaxis.ResultsThirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT.ConclusionThere are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.

Abstract Background Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence. Methods Adherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations. Results Past-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable. Conclusion IPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence. Clinical Trials Registration NCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

Abstract Introduction Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) derived disorders that can progress to acute myeloid leukemia (AML) at variable rates depending on macroenvironmental stressors and microenvironmental inflammatory cytokines. The total symptom score (TSS) and variant allele frequency (VAF) of mutations have proven valuable predictors of therapeutic response. Recently, we discovered inflammatory-cytokine-responsive ADAR1 RNA editing enzyme overexpression during MPN progression. However, dynamic prediction of clonal MPN stem cell fitness and progression to AML remains challenging. Methods We performed longitudinal 150-gene next-generation sequencing (NGS) analyses for 129 MPN patients. We developed single-cell RNA Editing ADAR1 Deaminase Activation Responsive (READAR) platforms to quantify ADAR1 activity with a novel ADAR1 nanoluc-GFP reporter assay, whole transcriptome RNA editome analyses, and MPN stem cell replating assays. To identify novel RNA editing sites, we performed whole genome sequencing on CD34+ cells from 43 MPN patients and whole transcriptome sequencing on FACS-purified HSC and progenitor cells from 32 MPN patients and 24 non-MPN controls. Results Sequential NGS analysis was performed with a median follow-up of 958 days (range 0-4214; interquartile range (IQR) 314-1350). On average, 6 NGS analyses (range 1-19; IQR 3-9) were performed for each patient. In our cohort, 58.9% of patients were JAK2 V617F+, while mutations in CALR and ASXL1 were observed in 11.6% and 14.0% of cases, respectively. In total, 44.2% (N=57) of patients in our cohort received Inrebic, with 56% reaching the maximum dose of 400mg. Notably, most patients on Inrebic were JAK2 V617F+ (N=38, 67.7%). In JAK2 V617F+ patients on Inrebic, 50% (n=19) experienced a reduction in the JAK2 V617F VAF from their peak value with a median drop of 16% (range 4-57). Our analyses using READAR platforms revealed increased RNA editing levels in JAK2 V617F+ patients from whole transcriptome sequencing analyses compared with JAK2 wild-type patients. Transduction of our ADAR1 nanoluc-GFP reporter into CD34+ cells from MPN patients (N=7), enabled us to quantify ADAR1 activity in an ex vivo setting. Moreover, CD34+ cells from MPN patient samples (n=7) treated in stromal co-cultures with ADAR1 inhibitor, Rebecsinib, demonstrated inhibition of self-renewal in replating assays. A significant reduction in ADAR1-GFP reporter activity was observed in MPN CD34+ cells following Rebecsinib treatment of stromal co-cultures. Also, humanized ADAR1-GFP-luciferase reporter AML mouse models showed a significant reduction in ADAR1 activity and leukemia stem cell self-renewal following Rebecsinib treatment. Conclusion These READAR platform results suggest that ADAR1 activity can be utilized to predict clonal MPN stem cell fitness and progression. Citation Format: Inge van der Werf, Larisa Balaian, Jessica Pham, Wenxue Ma, Athena Mohebbi, Emma Klacking, Antonio Ruiz, Karla Mack, John Mascarenhas, Thomas Whisenant, Ludmil Alexandrov, Sheldon Morris, Catriona Jamieson. RNA Editing ADAR1 Deaminase Activation Responsive (READAR) platforms for dynamic detection of clonal myeloproliferative neoplasm stem cell fitness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 263.

BACKGROUND:Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS:HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS:Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9-5.3), .24 (.060-.95), .27 (.12-.60), and .054 (.008-.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS:Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

Background Bacterial vaginosis (BV) is one of the most common vaginal dysbiosis in women aged 15–44 years old. Methods We administered a cross-sectional, single timepoint survey to women ages 18 years or older and who have had bacterial vaginosis (BV). Women completed an anonymous online survey evaluating the impact of BV on their quality of life, how effective different types of treatments were and the amount of self-diagnosed vs. provider diagnosed BV episodes they had. Results 62 participants completed the anonymous online survey. With a self-reported median number of BV episodes in the past year was 4 (IQR 1–7). Among these women 69.8% reported BV had a negative impact on their sexual health, 67.7% on their physical health, 74.6% on their mental health. More than half of the respondents had used probiotics with oral Lactobacillus sp. (53.2%), mainly by oral route, and over a third had used vaginal boric acid (37.1%). Most women were unaware of Lactobacillus crispatus . Lactobacillus probiotics were more likely to be tried by women who were negatively impacted by BV for overall quality of life ( p = 0.033), sexual health ( p = 0.002), and mental health ( p = 0.006) while boric acid use was more likely to be used by women who were negatively impacted by BV for their sexual health ( p = 0.008). Conclusions BV is associated with negative quality of life and the women most impacted are seeking alternative treatments such as probiotics (Lactobacillus) and boric acid. There needs to be improvements in BV treatment that include alternative therapy options that have demonstrated efficacy with standardized composition, formulation and dosage.

Background Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Methods Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. Results A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL. Conclusions Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials.

Background: Men who have sex with men (MSM) who use stimulants are at increased risk for HIV infection. Adherence to pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection. We evaluated the efficacy of the individualized Texting for Adherence Building (iTAB) intervention for PrEP adherence compared to standard of care (SoC) among 119 MSM who use stimulants (cocaine, methamphetamine and/or other amphetamine) from the California Collaborative Treatment Group 595 randomized control trial.Method: Three ordered levels of PrEP adherence (non-adherence, adequate adherence, and near-perfect adherence) were compared between intervention arms across study visits (weeks 12 and 48) using ordinal logistic regressions.Results: The effect of intervention arm was not significant in the final model; however, there was a 38% decrease in odds (OR = 0.62, p=.023) of having near-perfect adherence (versus non-adherence or adequate adherence) at week 48 compared to week 12, indicating a significant effect of time. In a follow-up analysis examining week 48 only, logistic regression examining PrEP adherence showed that receiving iTAB (compared to SoC) trended toward higher odds of near-perfect adherence relative to adequate adherence (OR = 2.48, p=.061). Higher HIV knowledge resulted in higher odds (OR = 1.72, p=.020) of near-perfect adherence (versus non-adherence or adequate adherence).Conclusion: HIV knowledge may influence PrEP adherence, and most notably, the iTAB intervention may support near-perfect adherence relative to adequate adherence.