PrEP Adherence Research Articles

Rationale and design of an integrated bio-behavioral approach to improve adherence to pre-exposure prophylaxis and HIV risk reduction among opioid-dependent people who use drugs: The CHRP-BB study

BackgroundFew primary HIV prevention strategies have successfully integrated both behavioral and biomedical components, with modest HIV risk reduction outcomes among opioid-dependent people who use drugs (PWUD). In response to this unmet need, we developed a brief, bio-behavioral intervention to simultaneously promote PrEP adherence and reduce HIV risk among opioid-dependent PWUD. MethodsUsing a Hybrid Type I implementation science design, we will examine the efficacy of the integrated bio-behavioral, Community-friendly Health Recovery Program (CHRP-BB) compared to a time-and-attention matched control condition among HIV-negative, opioid-dependent PWUD who are prescribed PrEP and enrolled in a methadone maintenance program (MMP) using a randomized controlled trial (RCT). Participants are assessed at baseline, immediately post-intervention (8 weeks) and follow-ups at weeks 20, 32, and 44 post-intervention. The primary outcome is biomedical (PrEP adherence), with secondary outcomes including behavioral (self-reported drug- and sex-related HIV risk behaviors), ongoing drug use (confirmed with urine drug testing), and related domains of the theoretical information-motivation-behavioral skills (IMB) model of behavior change related to PrEP adherence and HIV-transmission-risk reduction. Additionally, we will conduct a process evaluation of delivery/implementation of the intervention to collect valuable information to be used in future implementation. ConclusionsThis study will be among the first prospective trial to test an integrated bio-behavioral intervention to improve adherence to PrEP and HIV risk reduction among opioid-dependent PWUD.

An Electronic Pre-Exposure Prophylaxis Initiation and Maintenance Home Care System for Nonurban Young Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial.

BackgroundPre-exposure prophylaxis (PrEP) is highly efficacious for preventing HIV but has not yet been brought to scale among at-risk persons. In several clinical trials in urban areas, technology-based interventions have shown a positive impact on PrEP adherence. In rural and small-town areas in the United States, which often do not have geographically proximal access to PrEP providers, additional support may be needed. This may be particularly true for younger persons who are more likely to face multiple barriers to accessing PrEP services. Home-based care, accomplished through a tailored mobile phone app, specimen self-collection (SSC), and interactive video consultations, could increase both PrEP initiation and persistence in care.ObjectiveThe goal of this study is to assess the initiation and persistence in PrEP care for those randomized to a home-care intervention (electronic PrEP, ePrEP) relative to those assigned to the standard of care (control) condition. We will conduct additional assessments, including quantitative and qualitative analyses, to contextualize trial results and facilitate scale-up.MethodsThis 2-arm, randomized controlled trial will enroll young men who have sex with men (YMSM) aged between 18 and 24 years from rural areas of Georgia, Mississippi, and North Carolina. The trial will seek to recruit a diverse sample, targeting 50% participation among highly impacted groups of black or Latino men who have sex with men. Intervention participants will receive a study app that incorporates a messaging platform, a scheduling and milestone-based tracking system for PrEP care progress, electronic behavioral surveys, and interactive video consultations with a clinician. Complemented by SSC kits mailed to laboratories for standard PrEP-related monitoring, the ePrEP system will allow participants to access PrEP care without leaving their homes. YMSM randomized to the control condition will receive a listing of nearest local PrEP providers to receive standard PrEP care. Both groups will complete quarterly electronic surveys. The primary outcome, assessed at 6 and 12 months after randomization, will be the difference in the proportion of intervention versus control participants that achieve protective levels of the active metabolite of oral PrEP (tenofovir diphosphate in dried blood spots).ResultsEnrollment will begin in May 2019, with study completion in 2022.ConclusionsThis trial will determine whether home PrEP care provided through an app-based platform is an efficacious means of expanding access to PrEP care for a diverse group of YMSM in rural and small-town areas of the United States.Trial RegistrationClinicalTrials.gov NCT03729570; https://clinicaltrials.gov/ct2/show/NCT03729570 (Archived by WebCite at http://www.webcitation.org/78RE2Qizf)International Registered Report Identifier (IRRID)PRR1-10.2196/13982

Predictors of PrEP Uptake Among Patients with Equivalent Access.

Increasing PrEP adoption for eligible individuals is critical, but limited research has examined individual-level factors that might be amenable to educational or behavioral intervention. Using data from a PrEP demonstration project conducted at a community health center, we examined differences in behavioral and psychosocial factors between patients offered PrEP who chose to accept it and those who declined. In a multivariable model, the odds of accepting PrEP were higher among those with an HIV-positive main partner, greater risk behavior in the past 3months, and higher HIV risk perception. PrEP adoption was positively associated with PrEP adherence self-efficacy and negatively associated with perceived sensitivity to medicines. These psychological variables were associated with measures of PrEP- and HIV-related stigma. In the multivariable model, there were no differences in PrEP adoption by demographic factors or socioeconomic status. Data suggest that patients' decisions about PrEP uptake may be impacted not only by objective and subjective HIV risk, but also by psychological variables such as stigma beliefs, medication beliefs, and self-efficacy.

2271. Adherence to Pre-Exposure Prophylaxis Is Associated With Sexually Transmitted Infections Among Men Who Have Sex With Men in the Deep South

BackgroundPre-exposure prophylaxis (PrEP) reduces HIV acquisition, but there are reports of high sexually transmitted infection (STI) rates among PrEP clients, possibly related to high-risk sexual behaviors (risk compensation). The study objective was to identify the prevalence and facilitators of STIs among men who have sex with men (MSM) at a Deep South PrEP clinic.MethodsThis was a retrospective analysis of MSM aged ≥18 years receiving STI testing at a university-affiliated PrEP clinic in Birmingham, AL from 2014 to 2018. Clients were screened for gonorrhea and chlamydia in the oropharynx, urine, and rectum by nucleic acid amplification test and syphilis by serological testing at least every 6 months. Results of STI testing and biannual patient-reported outcomes (PROs) for condomless anal sex, numbers of sexual partners within the last 3 months, and PrEP adherence were analyzed. The outcome of interest was any positive STI. We evaluated the association of STIs with these PROs using logistic regression.Results141 MSM met study criteria: 29 (21%) were age 18–24, 39 (28%) identified as black, 25 (18%) reported consistent condom use, 22 (17%) reported >7 sexual partners in the past 3 months, 97 (69%) were prescribed PrEP, and 41 (29%) had at least one positive STI test. By univariate analysis, sexual partner number >7 and PrEP adherence were significantly associated with STIs; age and race were not. In multivariable analysis (Table 1), >7 sexual partners and PrEP adherence were independently associated with STI infection.ConclusionIn a university-based PrEP Clinic in the Deep South, STIs were common in MSM. Our findings suggest that risky sexual behaviors among PrEP clients contribute to STIs, especially for those reporting PrEP adherence and high number of sexual partners, and highlight STI prevention opportunities.Table 1:Multivariable Analysis of STIs Among PrEP Clients at a University-affiliated PrEP ClinicWith STI N (%)Odds Ratio (95% CI)Consistent Condom useYes*5 (14)No28 (76)1.6 (0.5–5.2)Number partners/3 months02 (5)3.5 (0.3–38.3)1*5 (13)2–718 (46)1.7 (0.5–5.4)>714 (36)9.7 (2.4–40.2)AdherenceNot on PrEP*7 (17)Missed dose 0–2 weeks ago5 (12)1.2 (0.3–5.1)Missed Dose >2 weeks ago29 (71)4.7 (1.4-15.4) *denotes referentDisclosures All authors: No reported disclosures.

1298. Acquisition of TDF-Susceptible HIV Despite High Level Adherence to Daily TDF/FTC PrEP as Measured by Dried Blood Spot (DBS) and Segmental Hair Analysis: A Case Report

BackgroundPre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (TFV) disoproxil fumarate (FTC/TDF) is highly protective against HIV infection. We report the second case of acquisition of TDF-susceptible HIV despite high adherence to PrEP, confirmed by drug level testing.MethodsPrEP adherence was assessed by measuring FTC/TDF metabolites in dried blood spots (DBS) and FTC/TFV concentrations in segments of scalp hair. Genotypic and phenotypic resistance were evaluated. HIV partner services (PS) and HIV sequences reported to HIV surveillance with a genetic distance ≤1.5% (by HIV-Trace) identified likely transmission partners.ResultsA 21-year-old Latino man presented 13 months after PrEP initiation. He was HIV negative by rapid HIV antibody (Ab) and HIV RNA pooling (detection limit ~40 copies/mL) at PrEP initiation and at months 3, 6, and 10. At the 13-month visit, he was asymptomatic and his rapid HIV Ab was negative. Five days later, his HIV RNA was reported as positive (559 copies/mL). He was notified of the result, linked to care and immediately started antiretroviral treatment (ART), at which point his RNA was 1544 copies/mL and his HIV Ab test was positive. The HIV genotype had M184V, L74V and K103N mutations and phenotypic susceptibility to TDF. TFV/FTC levels by LC-MS/MS measured in 1 cm segments of hair collected at ART initiation indicated consistently high PrEP adherence in each of the preceding 6 months. TFV-diphosphate and FTC-triphosphate levels in DBS collected 2 days after ART initiation were 1012 fmol/punch and 0.266 pmol/punch, confirming high adherence over the preceding 6 weeks. Between PrEP initiation and HIV acquisition, he had 1 episode of urethral chlamydia and three episodes of urethral gonorrhea. The likely transmission partner, named during PS, had no history of viral suppression in HIV surveillance and harbored the same resistance mutations, with a genetic distance between the two patients of 0.66%. The partner was re-linked to care and had a current HIV RNA of 15,130 copies/mL.ConclusionAcquisition of TDF-susceptible HIV infection can occur despite high PrEP adherence. Quarterly HIV and STD screening of patients on PrEP, combined with prompt linkage to care and PS for those diagnosed with HIV, facilitates early diagnosis and prevents further transmission of HIV.Disclosures S. E. Cohen, Gilead: Investigator in PrEP study for which Gilead donated drug, donated study drug and paid for drug testing during the PrEP demo project, of which I was a co-PI (the study has ended). S. Lee, Viiv Healthcare: Investigator, Research grant. Gilead Sciences: Investigator, Research grant. P. Anderson, Gilead: Consultant and Investigator, funds were paid to the institution for contract work and grant support and Research support. D. Havlir, Gilead: Investigator, Gilead Sciences provides antiretroviral therapy for a NIH funded study that she is conducting and Research support.

Predictors of Art and PrEP Adherence and Medication-Taking Practices and Preferences to Inform Development of a Wrist-Worn Adherence System.

We examined adherence, medication-taking practices, and preferences to inform development of a wrist-worn adherence system. Two convenience samples of persons taking antiretroviral therapy and HIV pre-exposure prophylaxis completed a survey. Additional online questions asked about willingness to use a wrist-worn device and reminder and feedback preferences. Among 225 participants, 13% reported adherence < 90%; this was associated with younger age and clinic sample. Compared to pill bottle-using participants, mediset users less commonly reported adherence < 90% (aOR = 0.16, p = .02), and blister pack users (aOR = 6.3, p = .02) and pill roll users (aOR = 3.3, p = .04) more commonly reported adherence < 90%. Sixty-two percent of the online participants reporting adherence (< 100%) had some interest in receiving adherence reminders, including 42% with interest in receiving reminders by smartwatch notifications. Although confounders are likely, formative work identified potential users and interest in using a wrist-worn adherence system. Future work will determine its acceptability and efficacy.

A Low Residue Diet with a Split Dose Bowel Prep Is Effective in Improving Bowel Prep Adequacy in a Veteranʼs Affairs Endoscopy Unit

Introduction: To achieve an effective colon cancer screening program, it has been proposed that GI labs should have an adequate bowel prep for >85% of exams. The aim of this study is to compare the efficacy of standard prep involving 2 days of clear liquid diet (CLD) followed by polyethylene glycol (PEG) prep on the night prior to procedure with a modified prep involving a low residue diet (LRD) for 5 days leading up to the procedure followed by 1 day of CLD and a split prep with PEG. Secondary aim is to assess the impact on adequacy of bowel prep. Methods: This study has pre-post study design evaluating all colonoscopies before and after an institutional policy change in the method of bowel preparation. All patients who received outpatient colonoscopies at the Atlanta VA Medical Center during May, 2016 and May to June, 2017 were included in this study. Patients who received alternative prep instructions were excluded from this study. Procedures aborted for reasons unrelated to prep were excluded. Pre-procedure nurses queried patients about adherence to split prep instructions and adherence to LRD. The data was analyzed by a statistician using frequency tables that were produced to examine the overall distributions of gender, race, type of prep, and prep quality among the study population. Chi square tests of association were applied to cross-tabulated data to detect associations between overall prep quality and a set of relevant variables including type of prep and completion prep and consumption of LRD. Estimated odds ratios with corresponding 95% confidence intervals were considered to indicate strong association. Results: A total 506 patients met inclusion criteria. The bowel prep was adequate significantly more often in modified prep patients compared to standard prep patients (87% vs 79.7%, p=0.017). Among modified prep patients, the LRD produced an adequate prep more often than without the diet (90.1% vs 77%, p=0.005). Adequacy rates were highest in those who followed the LRD, irrespective of completing split prep instructions or not (90.2% vs 88.9%). Conclusion: Our study confirms that adherence to a split prep results in higher rates of adequate bowel prep. However, adding a LRD for 5 days leading up to the colonoscopy improves the adequacy of the bowel prep beyond split prep alone. These novel findings support adding LRD to increase bowel prep adequacy rates.1066_A Figure 1. Bowel Prep Quality based on type of prep1066_B Figure 2. Modified Bowel Prep Quality based low residue diet1066_C Figure 3. Modified Bowel Prep Quality based on type of prep and diet

Smartphone-Based Contingency Management Intervention to Improve Pre-Exposure Prophylaxis Adherence: Pilot Trial.

BackgroundPre-exposure prophylaxis (PrEP) provides a strong preventative benefit to individuals at risk for HIV. While PrEP adherence is highly correlated with its efficacy, adherence rates are variable both across and within persons.ObjectiveThe objective of this study was to develop and pilot-test a smartphone-based intervention, known as mSMART, that targets PrEP adherence. mSMART provides contingency management in the form of monetary incentives for daily PrEP adherence based on a real-time adherence assessment using a camera-based medication event-monitoring tool as well as medication reminders, PrEP education, individualized behavioral strategies to address PrEP adherence barriers, and medication adherence feedback.MethodsThis was a 4-week open-label, phase I trial in a community sample of young men who have sex with men already on PrEP (N=10).ResultsAlthough adherence composite scores corresponding to PrEP biomarkers indicated that 90% (9/10) of the sample already had an acceptable baseline adherence in the protective range, by the end of the 4-week period, the scores improved for 30% (3/10) of the sample—adherence did not worsen for any participants. Participants reported mean PrEP adherence rates of 91% via daily entries in mSMART. At the end of the 4-week period, participants indicated acceptable ratings of satisfaction, usability, and willingness to recommend mSMART to others. There were no technical difficulties associated with smartphone compatibility, user misunderstandings about mSMART features that interfered with daily use, or study attrition.ConclusionsThis study is the first to apply contingency management to PrEP adherence. Findings indicated that mSMART is feasible and acceptable. Such an adherence intervention administered via a user-friendly smartphone app can allow for widespread dissemination. Future efficacy trials are needed.Trial RegistrationClinicalTrials.gov NCT02895893; https://clinicaltrials.gov/ct2/show/NCT02895893 (Accessed by Webcite at http://www.webcitation.org/72JskjDJq)

Barriers and facilitators to PrEP for transwomen in Brazil

ABSTRACTPre-exposure prophylaxis (PrEP) is an important biomedical intervention that may help reduce the risk of HIV transmission among transwomen. To date, little research is available to inform interventions to increase uptake and adherence to PrEP among transwomen, especially in places outside the U.S. We conducted a qualitative study in 2015 with 34 adult transwomen in Rio de Janeiro, Brazil and assessed awareness, interest, barriers and facilitators to PrEP uptake and adherence for transwomen. Almost one third of participants had heard of PrEP, and most were interested and thought it would be beneficial for transwomen in their community. Barriers to PrEP included fear of being HIV positive resulting in low HIV testing and concerns about the ability to adhere to a daily PrEP regimen. The most prominent barrier to uptake was past experiences of transgender-identity related discrimination in the universal health care system that reduced willingness to seek PrEP or health care in general. Participants recommended technological solutions to PrEP health education information that could address uptake and adherence. This study informs efforts to increase PrEP use among transwomen in Brazil.

Development and Validation of an Immunoassay for Tenofovir in Urine as a Real-Time Metric of Antiretroviral Adherence

BackgroundPharmacologic adherence measures were critical to the interpretation of the tenofovir (TFV)-disoproxil-fumarate/emtricitabine (TDF/FTC) PrEP trials. These measures are being incorporated into PrEP demonstration projects, but currently-available metrics in plasma, cells, hair or urine involve expensive and time-intensive mass-spectrometry (MS)-based methods. No point-of-care method to assess PrEP adherence in real-time has yet been implemented. Antibody-based tests allow for low-cost, easy-to-perform, point-of-care drug detection. In this study, we developed an antibody-based TFV immunoassay and evaluated its test characteristics among individuals taking TDF/FTC. MethodsWe synthesized possible immunogens based on TFV's molecular structure, injected rabbits with the conjugated derivatives, and bled them monthly for subsequent ELISA-testing for TFV-specific antibodies. We purified an antibody with specific TFV binding and created dose–response curves for ELISA-quantification. We then quantified TFV in urine from human participants not taking TDF/FTC and from individuals taking daily TDF/FTC 300 mg/200 mg for 7 days with a 7-day washout period using ELISA with this TFV-specific antibody. ELISA results were compared with the gold-standard test for TFV detection/quantification using liquid-chromatography-tandem-MS (LC–MS/MS). FindingsNone of the urine samples from 115 participants not taking TDF/FTC showed ELISA- reactivity, indicating 100% specificity (95% CI 97–100%) of the immunoassay. Among participants taking TDF/FTC, 67 of 70 samples positive by LC–MS/MS were positive by the ELISA-immunoassay for an estimated diagnostic sensitivity of 96% (95% CI 88–99%). The precision of the assay was high (coefficient of variation<15%). The rank correlation between ELISA and LC–MS/MS values in the 70 quantitative urine TFV levels positive by LC–MS/MS across a wide range of concentrations among participants on TDF/FTC was high (r = 0.96). InterpretationOur antibody-based immunoassay for measuring TFV in urine performed well compared to the gold-standard of LC–MS/MS among individuals taking TDF/FTC. A sensitive and specific immunoassay paves the way for real-time monitoring/feedback on recent adherence to TFV-based regimens, which should optimize interpretation and outcomes during PrEP and ART roll-out. FundingNIAID/NIH 2R01AI098472.

Patterns of Oral PrEP Adherence and HIV Risk Among Eastern African Women in HIV Serodiscordant Partnerships.

Understanding how women use PrEP is important for developing successful implementation programs. We hypothesized there are distinct patterns of adherence, related to HIV risk and other factors. We identified patterns of PrEP adherence and HIV risk behavior over the first 6months of PrEP use, using data from 233 HIV-uninfected women in high-risk serodiscordant couples in a demonstration project in Kenya & Uganda. We modeled PrEP adherence, assessed by daily electronic monitoring, and HIV risk behavior using group-based trajectory models. We tested baseline covariates and risk behavior group as predictors of adherence patterns. There were four distinct adherence patterns: high steady adherence (55% of population), moderate steady (29%), late declining (8%), and early declining (9%). No baseline characteristics significantly differed between adherence patterns. Adherence patterns differed in average weekly doses (6.7 vs 5.4 vs 4.1 vs 1.5, respectively). Two risk behavior groups were identified: steady HIV risk (78% of population) and declining (22%). Compared to women with declining HIV risk behavior, women with steady risk behavior were more likely to have high steady adherence (61% vs 35%) and less likely to have early (6% vs 17%) or late (4% vs 19%) declining adherence. Women's use of PrEP was associated with concurrent HIV risk behavior; higher risk was associated with higher, sustained adherence.

A Simple Pre-Exposure Prophylaxis (PrEP) Optimization Intervention for Health Care Providers Prescribing PrEP: Pilot Study.

BackgroundPre-exposure prophylaxis (PrEP) has been shown to be highly effective for the prevention of HIV in clinical trials and demonstration projects, but PrEP uptake and adherence outside of these settings in the United States has been limited. Lack of knowledge and willingness of health care providers (HCPs) to prescribe PrEP is an important barrier to implementation.ObjectiveThe objective of this study was to describe and examine the feasibility and acceptability of a PrEP Optimization Intervention (PrEP-OI) targeted at HCPs. The ultimate purpose of this intervention was to increase PrEP uptake, adherence, and persistence among those at risk for HIV acquisition.MethodsThis intervention included the following: (1) a Web-based panel management tool called PrEP-Rx, which provides comprehensive HIV risk assessment, automates reminders for follow-up, and reports patients’ history of PrEP use; and (2) centralized PrEP coordination by a clinical support staff member (ie, the PrEP coordinator) who can identify individuals at risk for HIV, provide medical insurance navigation, and support multiple HCPs. Feasibility was evaluated based on HCPs’ ability to log in to PrEP-Rx and use it as needed. Acceptability was assessed via individual formative qualitative interviews with HCPs after 1 month of the intervention.ResultsThe intervention was feasible and acceptable among HCPs (N=6). HCPs identified system-level barriers to PrEP provision, many of which can be addressed by this intervention. HCPs noted that the intervention improved their PrEP knowledge; increased ease of PrEP prescription; and was likely to improve patient engagement and retention in care, enhance communication with patients, and improve patient monitoring and follow-up.ConclusionsGiven the critical role HCPs serve in disseminating PrEP, we created an easy-to-use PrEP optimization intervention deemed feasible and acceptable to providers. Further research on this tool and its ability to impact the PrEP continuum of care is needed.

A systematic evaluation of mobile apps to improve the uptake of and adherence to HIV pre-exposure prophylaxis.

The Google Play store and Apple App store were systematically searched for currently available PrEP-related apps. A qualitative evaluation was conducted on apps that met the inclusion criteria for the presence of features that can contribute to PrEP uptake and adherence, and the quality of apps was assessed using the Mobile Apps Rating Scale (MARS) tool. From the systematic search, less than 2% (11/621) of the identified apps were relevant to improving PrEP uptake and adherence. Demonstrating a moderate capacity for facilitating PrEP use, the 11 PrEP-related apps, on average, contained features that addressed two of four factors that can contribute to the uptake of PrEP, particularly features that provided comprehensive information on PrEP and resources to locate providers and clinics offering PrEP services. Findings from the app quality assessment suggested that existing PrEP-related apps are of acceptable quality (mean overall MARS score: 3.2 on a five-point scale). Overall, currently available mobile apps for PrEP demonstrate some promise as potential avenues for increasing PrEP uptake and adherence among persons at-risk for HIV infection.

Development and Validation of an Immunoassay for Tenofovir in Urine as a Real-Time Metric of Antiretroviral Adherence

BACKGROUND: Pharmacologic adherence measures were critical to the interpretation of the tenofovir (TFV)-disoproxil-fumarate/emtricitabine (TDF/FTC) PrEP trials. These measures are being incorporated into PrEP demonstration projects, but currently-available metrics in plasma, cells, hair or urine involve expensive and time-intensive mass-spectrometry (MS)-based methods. No point-of-care method to assess PrEP adherence in real-time has yet been implemented. Antibody-based tests allow for low-cost, easy-to-perform, point-of-care drug detection. In this study, we developed an antibody-based TFV immunoassay and evaluated its test characteristics among individuals taking TDF/FTC. METHODS: We synthesized possible immunogens based on TFV's molecular structure, injected rabbits with the conjugated derivatives, and bled them monthly for subsequent ELISA-testing for TFV-specific antibodies. We purified an antibody with specific TFV binding and created dose-response curves for ELISA-quantification. We then quantified TFV in urine from human participants not taking TDF/FTC and from individuals taking daily TDF/FTC 300mg/200mg for 7 days with a 7-day washout period using ELISA with this TFV-specific antibody. ELISA results were compared with the gold-standard test for TFV detection/quantification using liquid-chromatography-tandem-MS (LC-MS/MS). FINDINGS: None of the urine samples from 115 participants not taking TDF/FTC showed ELISA- reactivity, indicating 100% specificity (95% CI 97-100%) of the immunoassay. Among participants taking TDF/FTC, 67 of 70 samples positive by LC-MS/MS were positive by the ELISA-immunoassay for an estimated diagnostic sensitivity of 96% (95% CI 88-99%). The precision of the assay was high (coefficient of variation <15%). The rank correlation between ELISA and LC-MS/MS values in the 70 quantitative urine TFV levels positive by LC-MS/MS across a wide range of concentrations among participants on TDF/FTC was high (r=0·96). INTERPRETATION: Our antibody-based immunoassay for measuring TFV in urine performed well compared to the gold-standard of LC-MS/MS among individuals taking TDF/FTC. A sensitive and specific immunoassay paves the way for real-time monitoring/feedback on recent adherence to TFV-based regimens, which should optimize interpretation and outcomes during PrEP and ART roll-out. Funding: NIAID/NIH 2R01AI098472 Conflict of Interest: None of the authors have any conflicts of interests to report Ethical Approval Statement: The UCSF Committee on Human Research approved the study (UCSF Institutional Review Board study #17-21617)

Utility of Different Adherence Measures for PrEP: Patterns and Incremental Value

Measuring PrEP adherence remains challenging. In 2009–2010, the International AIDS Vaccine Initiative randomized phase II trial participants to daily tenofovir disoproxil fumarate/emtricitabine or placebo in Uganda and Kenya. Adherence was measured by electronic monitoring (EM), self-report (SR), and drug concentrations in plasma and hair. Each adherence measure was categorised as low, moderate, or high and also considered continuously; the incremental value of combining measures was determined. Forty-five participants were followed over 4 months. Discrimination for EM adherence by area under receiver operating curves (AROC) was poor for SR (0.53) and best for hair (AROC 0.85). When combining hair with plasma or hair with self-report, discrimination was improved (AROC > 0.9). Self-reported adherence was of low utility by itself. Hair level was the single best PK measure to predict EM-assessed adherence; the other measurements had lower discrimination values. Combining short-term (plasma) and long-term (hair) metrics could be useful to assess patterns of drug-taking in the context of PrEP.

Recent HIV Risk Behavior and Partnership Type Predict PrEP Adherence in Men Who Have Sex with Men

BackgroundIndividuals engaging in higher risk behavior are often more adherent to PrEP but it is unclear if partnership type itself affects PrEP adherence. We examined the effect of recent HIV risk behaviors and partnership type on PrEP adherence in men who have sex with men (MSM) taking PrEP.MethodsCCTG 595 is a 48-week PrEP demonstration study of 398 HIV− at-risk MSM. At baseline and week 48, HIV risk score was estimated as the probability of seroconversion over the next year based on number of condomless anal sex acts with HIV+/unknown partners in the last month and any STI diagnosed at study visit. HIV risk score was categorized as low (<0.12), moderate (0.12−0.59) and high (>0.59) risk based on population seroconversion probabilities. Partnership type was assigned as no/single HIV− partner, single HIV+ partner, or multiple partners of any serostatus in the past 3 months. PrEP adherence was estimated by intracellular tenofovir-diphosphate (TFV-DP) levels as a continuous variable at week 48. Statistical methods included McNemar’s test, Wilcoxon rank-sum test, and linear regression model where appropriate.ResultsOf 313 MSM who completed week 48, there was no significant change in HIV risk category from baseline to week 48 (low: 44 to 42%; moderate: 27 to 24%; high: 28 to 34%; P = 0.25). There was a significant change in partnership type, with the proportion of those with no or single HIV− partnerships increasing (1 to 9%, P < 0.001). In univariate analysis, moderate and high-risk groups had higher TFV-DP levels than the low-risk group at week 48 (P = 0.018). Participants with no/single HIV− partner had significantly lower TFV-DP levels than those with one HIV+ partner or multiple partners (P = 0.007). In a multivariable linear regression model, only low-risk partnerships remained significant where no/single HIV− partnerships were associated with lower TFV-DP levels (mean difference = −344fmol/punch [−617, −71], P = 0.014).ConclusionAlthough there was a shift in partnership type towards lower risk partnerships, objective HIV risk behavior remained stable over time. Individuals with higher HIV risk behaviors and risk partnerships had higher TFV-DP levels suggesting maintained strong motivation for PrEP adherence. Thus, recent sexual risk behavior and partnership type may be important predictors of PrEP adherence in MSM.Disclosures All authors: No reported disclosures.

Frame me if you must: PrEP framing and the impact on adherence to HIV Pre-exposure Prophylaxis

Background“PrEP whore” has been used both as a pejorative by PrEP opponents in the gay community and, reactively, by PrEP advocates as a method to reclaim the label from stigmatization and “slut-shaming.” The actual prevalence and impact of such PrEP-directed stigma on adherence have been insufficiently studied.MethodsCCTG 595 was a randomized controlled PrEP demonstration project in 398 HIV-uninfected MSM and transwomen. Intracellular tenofovir-diphosphate (TFV-DP) levels at weeks 12 and 48 were used as a continuous measure of adherence. At study visits, participants were asked to describe how they perceived others’ reactions to them being on PrEP. These perceptions were categorized a priori as either “positively framed,” “negatively framed,” or both. We used Wilcoxon rank-sum to determine the association between positive and negative framing and TFV-DP levels at weeks 12 and 48.ResultsBy week 4, 29% of participants reported perceiving positive reactions from members of their social groups, 5% negative, and 6% both. Reporting decreased over 48 weeks, but positive reactions were consistently reported more than negative. At week 12, no differences in mean TFV-DP levels were observed in participants with positively-framed reactions compared with those reporting no outcome or only negatively-framed (1338 [IQR, 1036-1609] vs. 1281 [946-1489] fmol/punch, P = 0.17). Additionally, no differences were observed in those with negative reactions vs. those without (1209 [977–1427] vs. 1303 [964–1545], P = 0.58). At week 48, mean TFV-DP levels trended toward being higher among those that report any reaction, regardless if positive (1335 [909–1665] vs. 1179 [841–1455], P = 0.09) or negative (1377 [1054–1603] vs. 1192 [838–1486], P = 0.10) than those reporting no reaction. At week 48, 46% of participants reported experiencing some form of PrEP-directed judgment, 23% reported being called “PrEP whore,” and 21% avoiding disclosing PrEP use.ConclusionOver 48 weeks, nearly half of participants reported some form of judgment or stigmatization as a consequence of PrEP use. However, individuals more frequently perceived positively framed reactions to being on PrEP than negative. Importantly, long-term PrEP adherence does not appear to suffer as a result of negative PrEP framing.Disclosures All authors: No reported disclosures.

Commitment issues: PrEP adherence in injecting drug users

Commitment issues: PrEP adherence in injecting drug users

A Cost-effectiveness Analysis of Preexposure Prophylaxis for the Prevention of HIV Among Los Angeles County Men Who Have Sex With Men.

Substantial gaps remain in understanding the trade-offs between the costs and benefits of choosing alternative human immunodeficiency virus (HIV) prevention strategies, including test-and-treat (expanded HIV testing combined with immediate treatment) and PrEP (initiation of preexposure prophylaxis by high-risk uninfected individuals) strategies. We develop a mathematical epidemiological model to simulate HIV incidence among men residing in Los Angeles County, California, aged 15-65 years, who have sex with men. We combine these incidence data with an economic model to estimate the discounted cost, effectiveness (quality-adjusted life-years [QALYs]), and incremental cost-effectiveness ratios of various HIV prevention strategies using a societal perspective and a lifetime horizon. PrEP and test-and-treat yield the largest reductions in HIV incidence, and are highly cost-effective ($27 863/QALY and $19 302/QALY, respectively) relative to status quo and at a US willingness-to-pay threshold of $150 000/QALY saved. Status quo and 12 test-and-treat and PrEP strategies determine the frontier for efficient decisions. More aggressive strategies are costlier, but more effective, albeit with diminishing returns. The relative effectiveness of PrEP is sensitive to the initial HIV prevalence rate, PrEP and antiretroviral therapy (ART) adherence and initiation rates, the probabilities of HIV transmission, and the rates of sexual partner mixing. PrEP and test-and-treat offer cost-effective alternatives to the status quo. The success of these strategies depends on ART and PrEP adherence and initiation rates. The lack of evidence on adherence behaviors toward PrEP, therefore, warrants further studies.

Project PrEPARE: High Levels of Medication Adherence with Continued Condomless Sex in U.S. Men who Have Sex with Men in an Oral PrEP Adherence Trial

AIDS Research and Human RetrovirusesVol. 30, No. S1 Risk and Prevention for MSMProject PrEPARE: High Levels of Medication Adherence with Continued Condomless Sex in U.S. Men who Have Sex with Men in an Oral PrEP Adherence TrialKenneth H. Mayer, Steven Safren, Jessica Haberer, Steven Elsesser, William Clarke, Craig W. Hendrix, Mark Marzinke, and Matthew J. MimiagaKenneth H. MayerFenway Health, The Fenway Institute, Boston, MA, United StatesBeth Israel Deaconess Medical Center, Division of Infectious Diseases, Boston, MA, United StatesHarvard Medical School, Medicine, Boston, MA, United StatesSearch for more papers by this author, Steven SafrenFenway Health, The Fenway Institute, Boston, MA, United StatesMassachusetts General Hospital, Psychiatry, Boston, MA, United StatesHarvard Medical School, Psychiatry, Boston, MA, United StatesSearch for more papers by this author, Jessica HabererHarvard Medical School, Medicine, Boston, MA, United StatesMassachusetts General Hospital, Medicine, Boston, MA, United StatesSearch for more papers by this author, Steven ElsesserFenway Health, The Fenway Institute, Boston, MA, United StatesSearch for more papers by this author, William ClarkeJohns Hopkins University School of Medicine, Pathology, Baltimore, MD, United StatesSearch for more papers by this author, Craig W. HendrixJohns Hopkins University School of Medicine, Pathology, Baltimore, MD, United StatesSearch for more papers by this author, Mark MarzinkeJohns Hopkins University School of Medicine, Pathology, Baltimore, MD, United StatesSearch for more papers by this author, and Matthew J. MimiagaFenway Health, The Fenway Institute, Boston, MA, United StatesMassachusetts General Hospital, Psychiatry, Boston, MA, United StatesHarvard School of Public Health, Epidemiology, Boston, MA, United StatesSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5032a.abstractAboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Project PrEPARE: High Levels of Medication Adherence with Continued Condomless Sex in U.S. Men who Have Sex with Men in an Oral PrEP Adherence Trial." AIDS Research and Human Retroviruses, 30(S1), pp. A23–A24FiguresReferencesRelatedDetailsCited ByDealing with pre-exposure prophylaxis-associated condom migration: changing the paradigm for men who have sex with menSexual Health, Vol. 14, No. 1Successful Implementation of HIV Preexposure Prophylaxis: Lessons Learned From Three Clinical Settings22 February 2016 | Current HIV/AIDS Reports, Vol. 13, No. 2 Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Kenneth H. Mayer, Steven Safren, Jessica Haberer, Steven Elsesser, William Clarke, Craig W. Hendrix, Mark Marzinke, and Matthew J. Mimiaga.Project PrEPARE: High Levels of Medication Adherence with Continued Condomless Sex in U.S. Men who Have Sex with Men in an Oral PrEP Adherence Trial.AIDS Research and Human Retroviruses.Oct 2014.A23-A24.http://doi.org/10.1089/aid.2014.5032a.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download