HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs.

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIVneg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin- BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVneg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIVposEVs) and plasma depleted of EVs (HIV PLdepEVs). HIVposEVs, but not HIV PLdepEVs or HIVnegEVs (EVs from HIVneg individuals), increased atherosclerosis in apoE-/- mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin- BMCs. Small RNA-seq identified EV-miRs overrepresented in HIVposEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVposEVs in vivo. Lin- BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3'UTR and as such is resistant to miR-mediated regulation showed protection against HIVposEVs-induced changes in lin- BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.

Rapid Identification and Investigation of an HIV Risk Network Among People Who Inject Drugs -Miami, FL, 2018.

Prevention of HIV outbreaks among people who inject drugs remains a challenge to ending the HIV epidemic in the United States. The first legal syringe services program (SSP) in Florida implemented routine screening in 2018 leading to the identification of ten anonymous HIV seroconversions. The SSP collaborated with the Department of Health to conduct an epidemiologic investigation. All seven acute HIV seroconversions were linked to care (86% within 30 days) and achieved viral suppression (mean 70 days). Six of the seven individuals are epidemiologically and/or socially linked to at least two other seroconversions. Analysis of the HIV genotypes revealed that two individuals are connected molecularly at 0.5% genetic distance. We identified a risk network with complex transmission dynamics that could not be explained by epidemiological methods or molecular analyses alone. Providing wrap-around services through the SSP, including routine screening, intensive linkage and patient navigation, could be an effective model for achieving viral suppression for people who inject drugs.

Implementation of an Immediate HIV Treatment Initiation Program in a Public/Academic Medical Center in the U.S. South: The Miami Test and Treat Rapid Response Program.

Test and Rapid Response Treatment (TRRT) linkage programs have demonstrated improved HIV suppression rates. This paper describes the design and implementation of the Miami TRRT initiative and its clinical impact. Assisted by a dedicated care navigator, patients receiving a reactive HIV rapid test at the Florida Department of Health STD Clinic were offered same-day HIV care at the University of Miami/Jackson Memorial Medical Center Adult HIV Outpatient Clinic. Patient retention and labs were tracked for 12 months. Of the 2337 individuals tested, 46 had a reactive HIV test; 41 (89%) consented to participate. For the 36 patients in continued care for a year, 33 (91.7%) achieved virological suppression (< 200 copies/mL) within 70 days of their reactive HIV rapid test; at 12 months, 35 (97.2%) remained suppressed, and mean CD4 T cell counts increased from 452 ± 266 to 597 ± 322 cells/mm3. The Miami TRRT initiative demonstrated that immediate linkage to care is feasible and improves retention and suppression in a public/academic medical center in the U.S. South.

Cutting edge: novel vaccination modality provides significant protection against mucosal infection by highly pathogenic simian immunodeficiency virus.

Vaccine-induced protection against infection by HIV or highly pathogenic and virulent SIV strains has been limited. In a proof-of-concept study, we show that a novel vaccine approach significantly protects rhesus macaques from mucosal infection by the highly pathogenic strain SIVmac251. We vaccinated three cohorts of 12 macaques each with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig. Cohort 1 was vaccinated with cells secreting gp96(SIV)Ig carrying SIV peptides. In addition, Cohort 2 received recombinant envelope protein SIV-gp120. Cohort 3 was injected with cells secreting gp96-Ig (no SIV Ags) vaccines. Cohort 2 was protected from infection. After seven rectal challenges with highly pathogenic SIVmac251, the hazard ratio was 0.27, corresponding to a highly significant, 73% reduced risk for viral acquisition. The apparent success of the novel vaccine modality recommends further study.

Preventing HIV infection: pre-exposure and postexposure prophylaxis.

Data supporting the use of pre-exposure prophylaxis (PrEP) and nonoccupational postexposure prophylaxis (nPEP) in the prevention of HIV infection after a sexual encounter continue to grow. In this review, we describe some of the research driving the various recommendations for use of antiretrovirals in prevention. In addition, current research is described regarding the establishment of viral reservoirs that argues for rethinking the timing for nPEP treatment. We discuss the variables that impact on the choice of prevention antiretrovirals, including drug distribution, drug transporters, and potential impact of race and ethnicity on these variables.

Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs.

BACKGROUND: The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. METHODS: The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copies/ml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copies/ml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed. DISCUSSION: The T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05208697. Trial registry name: Tele-Harm Reduction. Registration date: January 26, 2022.

Multilevel Determinants of Rapid Antiretroviral Treatment Implementation and Demand in Miami-Dade County.

BACKGROUND: Rapidly linking newly diagnosed HIV patients to antiretroviral treatment (ART) is the best practice for achieving optimal treatment outcomes, including viral suppression. However, rapid ART implementation varies throughout the United States, highlighting the importance of identifying rapid ART implementation determinants in US HIV epicenters, such as Miami-Dade County (MDC). METHODS: Clinic focus groups (N = 4 clinics) and patient interviews (N = 31 recently diagnosed patients) systematically and qualitatively assessed rapid ART implementation determinants in MDC. Independent coders analyzed focus groups and interviews using a directed content analysis approach guided by the Consolidated Framework for Implementation Research. RESULTS: For clinic stakeholders, key rapid ART implementation determinants included the following: complexity and adaptability (innovation characteristics); networks between clinics and patient needs rooted in structural inequities (outer setting); leadership and available resources (inner setting); staff/provider flexibility (characteristics of individuals); and appointing patient navigators and champions (process). For patients, key determinants included complexity and relative advantage of rapid treatment (innovation characteristics); patient needs and clinic networks (outer setting); provider knowledge and skills (inner setting); provider warmth and affirmation (characteristics of individuals); and need for improved outreach (process). CONCLUSIONS: Multilevel factors impact clinic implementation and patient demand for rapid ART in MDC. Informed by these factors, we identified potential implementation strategies to enhance rapid ART implementation throughout MDC. These implementation strategies can be tested in an implementation trial, enhancing the toolkit of strategies to ensure that evidence-based tools, particularly rapid ART, are readily available to the most impacted communities.

Abacavir antiretroviral therapy and indices of subclinical vascular disease in persons with HIV.

OBJECTIVE: Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. APPROACH: The 115 participants (63% men), aged 30-50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). RESULTS: No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. CONCLUSIONS: Findings indicate that ABC treatment of 30-50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.

M2HepPrEP: study protocol for a multi-site multi-setting randomized controlled trial of integrated HIV prevention and HCV care for PWID.

BACKGROUND: Opioid use is escalating in North America and comes with a multitude of health consequences, including HIV and hepatitis C virus (HCV) outbreaks among persons who inject drugs (PWID). HIV pre-exposure prophylaxis (PrEP) and HCV treatment regimens have transformative potential to address these co-occurring epidemics. Evaluation of innovative multi-modal approaches, integrating harm reduction, opioid agonist therapy (OAT), PrEP, and HCV treatment is required. The aim of this study is to assess the effectiveness of an on-site integrated care model where delivery of PrEP and HCV treatment for PWID takes places at syringe service programs (SSP) and OAT programs compared with referring PWID to clinical services in the community through a patient navigation model and to examine how structural factors interact with HIV prevention adherence and HCV treatment outcomes. METHODS: The Miami-Montreal Hepatitis C and Pre-Exposure Prophylaxis trial (M2HepPrEP) is an open-label, multi-site, multi-center, randomized, controlled, superiority trial with two parallel treatment arms. A total of 500 persons who injected drugs in the prior 6 months and are eligible for PrEP will be recruited in OAT clinics and SSP in Miami, FL, and Montréal, Québec. Participants will be randomized to either on-site care, with adherence counseling, or referral to off-site clinics assisted by a patient navigator. PrEP will be offered to all participants and HCV treatment to those HCV-infected. Co-primary endpoints will be (1) adherence to pre-exposure prophylaxis medication at 6 months post-randomization and (2) HCV sustained virological response (SVR) 12 weeks post-treatment completion among participants who were randomized within the HCV stratum. Up to 100 participants will be invited to participate in a semi-structured interview regarding perceptions of adherence barriers and facilitators, after their 6-month assessment. A simulation model-based cost-effectiveness analysis will be performed to determine the comparative value of the strategies being evaluated. DISCUSSION: The results of this study have the potential to demonstrate the effectiveness and cost-effectiveness of offering PrEP and HCV treatment in healthcare venues frequently attended by PWID. Testing the intervention in two urban centers with high disease burden among PWID, but with different healthcare system dynamics, will increase generalizability of findings. TRIAL REGISTRATION: Clinicaltrials.gov NCT03981445 . Trial registry name: Integrated HIV Prevention and HCV Care for PWID (M2HepPrEP). Registration date: June 10, 201.

Demographic and psychosocial factors associated with appointment attendance among HIV-positive outpatients.

Non-adherence to medical regimens is a critical threat to HIV-infected individuals. Persons living with HIV/AIDS must adhere to their outpatient medical appointments to benefit from continually improving HIV care regimens. The primary purpose of the present study was to identify individual and psychosocial characteristics associated with HIV-related medical appointment non-attendance. One hundred seventy eight adult participants attending the Outpatient Adult HIV/AIDS Immunology Clinic at Jackson Memorial Hospital (JMH) in Miami, Florida participated in the study. Scheduled and missed appointments obtained retrospectively over a 12-month period indicated that medical appointment non-attendance was a significant problem. Overall, 27.9% of scheduled appointments were missed during the study period. Young age and limited family support were predictors of non-attendance. These findings support those of others and highlight targeted intervention efforts to reduce appointment non-attendance among persons living with HIV/AIDS.

An academic center's delivery of care after the Haitian earthquake.

The Miller School of Medicine of the University of Miami and Project Medishare, an affiliated not-for-profit organization, provided a large-scale relief effort in Haiti after the earthquake of 12 January 2010. Their experience demonstrates that academic medical centers in proximity to natural disasters can help deliver effective medical care through a coordinated process involving mobilization of their own resources, establishment of focused management teams at home and on the ground with formal organizational oversight, and partnership with governmental and nongovernmental relief agencies. Proximity to the disaster area allows for prompt arrival of medical personnel and equipment. The recruitment and organized deployment of large numbers of local and national volunteers are indispensable parts of this effort. Multidisciplinary teams on short rotations can form the core of the medical response.

Harm reduction for the treatment of patients with severe injection-related infections: description of the Jackson SIRI Team.

INTRODUCTION: Hospitalizations for severe injection-related infections (SIRI), such as endocarditis, osteomyelitis, and skin and soft tissue infections (SSTI) are increasingly common. People who inject drugs (PWID) experiencing SIRIs often receive inadequate substance use disorder (SUD) treatment and lack of access to harm reduction services. This translates into lengthy hospitalizations with high rates of patient-directed discharge, readmissions, and post-hospitalization mortality. The purpose of this study was to describe the development of an integrated "SIRI Team" and its initial barriers and facilitators to success. MATERIALS AND METHODS: The Jackson SIRI Team was developed to improve both hospital and patient-level outcomes for individuals hospitalized with SIRIs at Jackson Memorial Hospital, a 1550-bed public hospital in Miami, Florida, United States. The SIRI Team provides integrated infectious disease and SUD treatment across the healthcare system starting from the inpatient setting and continuing for 90-days post-hospital discharge. The team uses a harm reduction approach, provides care coordination, focuses on access to medications for opioid use disorder (MOUD), and utilizes a variety of infection and addiction treatment modalities to suit each individual patient. RESULTS: Over the initial 8-months of the SIRI Team, 21 patients were treated with 20 surviving until discharge. Infections included osteomyelitis, endocarditis, bacteraemia/fungemia, SSTIs, and septic arthritis. All patients had OUD and 95% used stimulants. All patients were discharged on MOUD and 95% completed their prescribed antibiotic course. At 90-days post-discharge, 25% had been readmitted and 70% reported taking MOUD. CONCLUSIONS: A model of integrated infectious disease and SUD care for the treatment of SIRIs has the potential to improve infection and addiction outcomes. Providing attentive, patient-centered care, using a harm reduction approach can facilitate engagement of this marginalized population with the healthcare system.KEY MESSAGESIntegrated infectious disease and addiction treatment is a novel approach to treating severe injection-related infections.Harm reduction should be applied to treating patients with severe injection-related infections with a goal of facilitating antibiotic completion, remission from substance use disorder, and reducing hospital readmissions.

Acceptability, feasibility, and pilot results of the tele-harm reduction intervention for rapid initiation of antiretrovirals among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) have been a marginalized and a stigmatized population since the beginning of the AIDS epidemic and have not experienced the same life-changing benefits of antiretroviral therapy as others. Tele-Harm Reduction (THR) is a telehealth-enhanced, harm reduction intervention, delivered within a trusted SSP venue. It aims to facilitate initiation of care and achieve rapid HIV viral suppression among PWID living with HIV. METHODS: In this mixed-methods study, we employed the Practical, Robust, Implementation and Sustainability Model (PRISM) implementation science framework to identify multilevel barriers and facilitators to implementing the THR intervention. Focus groups (n = 2, 16 participants), stakeholder interviews (n = 7) and in-depth interviews were conducted with PWID living with HIV (n = 25). In addition, to assess feasibility and acceptability, we pilot tested the THR intervention and reported viral suppression at 6 months. RESULTS: Focus groups and stakeholder interviews revealed system and organizational level barriers to implementation including requirements for identification and in person visits, waiting times, stigma, case management inexperience, multiple electronic health records, and billing. A potential facilitator was using telehealth for case management and initial provider visit. In the in depth interviews conducted with PWID living with HIV, participants expressed that the SSP creates a convenient, comfortable, confidential environment for delivering multiple, non-stigmatizing PWID-specific services. 35 PWID living with HIV were enrolled in the pilot study, 35 initiated antiretroviral therapy, and 25 (78.1%) were virally suppressed at six months. CONCLUSION: Rooted in harm reduction, the THR intervention shows promise in being an acceptable and feasible intervention that may facilitate engagement in HIV care and viral suppression among PWID.

Quarterly screening optimizes detection of sexually transmitted infections when prescribing HIV preexposure prophylaxis.

OBJECTIVE: The optimal screening frequency of sexually transmitted infections (STIs) for MSM and transgender women (TGW) on HIV pre-exposure prophylaxis (PrEP) is unclear, with present guidelines recommending screening every 3-6 months. We aimed to determine the number of STIs for which treatment would have been delayed without quarterly screening. DESIGN: The US PrEP Demonstration Project was a prospective, open-label cohort study that evaluated PrEP delivery in STI clinics in San Francisco and Miami, and a community health center in Washington, DC. In all, 557 HIV-uninfected MSM and TGW were offered up to 48 weeks of PrEP and screened quarterly for STIs. METHODS: The proportion of gonorrhea, chlamydia, and syphilis infections for which treatment would have been delayed had screening been conducted every 6 versus every 3 months was determined by taking the number of asymptomatic STIs at weeks 12 and 36 divided by the total number of infections during the study follow-up period for each STI. RESULTS: Among the participants, 50.9% had an STI during follow-up. If screening had been conducted only semiannually or based on symptoms, identification of 34.3% of gonorrhea, 40.0% of chlamydia, and 20.4% of syphilis infections would have been delayed by up to 3 months. The vast majority of participants (89.2%) with asymptomatic STIs reported condomless anal sex and had a mean of 8.1 partners between quarterly visits. CONCLUSIONS: Quarterly STI screening among MSM on PrEP could prevent a substantial number of partners from being exposed to asymptomatic STIs, and decrease transmission.

Brief Report: Short-Term Adherence Marker to PrEP Predicts Future Nonretention in a Large PrEP Demo Project: Implications for Point-of-Care Adherence Testing.

BACKGROUND: Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine (FTC)-based pre-exposure prophylaxis (PrEP) were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays for TFV, which examine short-term adherence, are in development. However, the ability of poor short-term and long-term adherence to predict future PrEP nonretention is unknown. SETTING: Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project. METHODS: An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study nonretention. RESULTS: Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By the end of study, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating suboptimal long-term adherence (TFV-DP <700 fmol/punch). The strongest factor associated with future study nonretention using a binary drug-level cut-off was an undetectable DBS FTC-TP level (adjusted hazard ratio 6.3; 95% confidence interval 3.8 to 10.2). The suboptimal long-term adherence based on low DBS TFV-DP levels was also associated with nonretention (adjusted hazard ratio 4.3; 95% confidence interval: 2.4 to 7.6). CONCLUSIONS: Both short- and long-term metrics of PrEP adherence are strongly associated with future loss to follow-up in a U.S. demonstration project study. Short-term metrics of adherence, once available at the point-of-care, could be used to direct real-time tailored retention and adherence interventions.

Development of drug resistance mutations in patients on highly active antiretroviral therapy: does competitive advantage drive evolution.

Most physicians that treat individuals with HIV-1 disease are able to successfully suppress viral replication with the pharmacologic armamentarium available today. For the majority of patients this results in immune reconstitution and improved quality of life. However, a large fraction of these patients have transient elevations in their viral burden and even persistence of low-level viremia. In fact, many individuals whose viral load is suppressed to < 50 c/ml have evidence of low-level viral replication. The impact of low-level viremia and persistent viral replication is an area of significant study and interest owing to the potential for the development of drug resistance mutations. Here the fundamental question is whether and perhaps what factors provide a venue for the development of resistant virus. The concern is clearly the eventual progression of disease with the exhaustion of treatment options. The purpose of this review is to evaluate the current literature regarding the effect of low-level viremia on the development of drug resistance mutations. Herein, we discuss the impact of different levels of viral suppression on the development of mutations. In addition, we look at the role that resistance and fitness play in determining the survival of a breakthrough mutation within the background of drug.

Modelling the impact of new patient visits on risk adjusted access at 2 clinics.

OBJECTIVE: To evaluate the effect new outpatient clinic visits has on the availability of follow-up visits for established patients when patient visit frequency is risk adjusted. DATA SOURCES: Diagnosis codes for patients from 2 Internal Medicine Clinics were extracted through billing data. STUDY DESIGN: The HHS-HCC risk adjusted scores for each clinic were determined based upon the average of all clinic practitioners' profiles. These scores were then used to project encounter frequencies for established patients, and for new patients entering the clinic based on risk and time of entry into the clinics. PRINCIPAL FINDINGS: A distinct mean risk frequency distribution for physicians in each clinic could be defined providing model parameters. Within the model, follow-up visit utilization at the highest risk adjusted visit frequencies would require more follow-up slots than currently available when new patient no-show rates and annual patient loss are included. Patients seen at an intermediate or lower visit risk adjusted frequency could be accommodated when new patient no-show rates and annual patient clinic loss are considered. CONCLUSIONS: Value-based care is driven by control of cost while maintaining quality of care. In order to control cost, there has been a drive to increase visit frequency in primary care for those patients at increased risk. Adding new patients to primary care clinics limits the availability of follow-up slots that accrue over time for those at highest risk, thereby limiting disease and, potentially, cost control. If frequency of established care visits can be reduced by improved disease control, closing the practice to new patients, hiring health care extenders, or providing non-face to face care models then quality and cost of care may be improved.

Patterns and Correlates of Participant Retention in a Multi-City Pre-Exposure Prophylaxis Demonstration Project.

BACKGROUND: Safe and effective use of pre-exposure prophylaxis (PrEP) depends on retention in care after initial engagement. SETTING: The United States PrEP Demonstration Project offered daily oral tenofovir/emtricitabine to participants in San Francisco, Miami, and Washington, D.C. for 48 weeks from 2012 to 2014. METHODS: The Demo Project participants' patterns of retention were assigned to 1 of 3 categories: early loss to follow-up (ELTF) within the first 12 weeks of the study, retention throughout the study, or intermittent retention in which missed or delayed visits resulted in gaps in medication availability. For each group, baseline characteristics were tabulated. A two-step multivariable analysis was performed. RESULTS: Overall, 366/554 (66.1%) of enrolled participants were retained for all study visits, 127/554 (22.9%) had intermittent retention, and 61/554 (11.0%) ELTF. In multivariable analysis, Miami compared with San Francisco site was associated with ELTF rather than full retention [aOR 2.84; confidence interval (CI): 1.24 to 6.47] and also with intermittent rather than full retention (aOR 2.70; CI: 1.43 to 5.11). Younger age was associated with ELTF (aOR 1.80 for each 10-year decrement in age; CI: 1.26 to 2.57) and intermittent retention (aOR 1.47; CI: 1.17 to 1.84) compared with full retention. Factors associated with ELTF (but not intermittent retention) compared with full retention were black compared with white (aOR 3.32; CI: 1.09 to 10.16), reporting sex work (aOR 4.67; CI: 1.49 to 14.58), lack of regular employment (aOR 2.53; CI: 1.27 to 5.05), and lack of previous PrEP awareness (aOR 2.01; CI: 1.01 to 3.96). CONCLUSIONS: Tailored interventions addressing causes and risk factors for loss from PrEP care may improve retention and consistency of PrEP use.

Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project.

BACKGROUND: HIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings. SETTING: Demonstration project in 2 sexually transmitted infection clinics and a community health center. METHODS: We evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI). RESULTS: From October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR <70 mL/min/1.73 m; independent predictors of this outcome were age ≥40 years (OR 3.79, 95% CI: 1.43 to 10.03) and baseline eGFR <90 mL/min/1.73 m (OR 9.59, 3.69-24.94). CONCLUSIONS: In a demonstration setting, daily tenofovir-disoproxil-fumarate/emtricitabine PrEP leads to reduced CrCl and eGFR; however, these eGFR changes are based on very small changes in serum creatinine and seem to be nonprogressive after the first 12 weeks. Future studies are needed to understand the prognostic significance of these small changes.

Healthcare Access and PrEP Continuation in San Francisco and Miami After the US PrEP Demo Project.

BACKGROUND: Pre-exposure prophylaxis (PrEP) for prevention of HIV infection has demonstrated efficacy in randomized controlled trials and in demonstration projects. For PrEP implementation to result in significant reductions in HIV incidence for men who have sex with men in the United States, sufficient access to PrEP care and continued engagement outside of demonstration projects is required. METHODS: We report the results of a follow-up survey of 173 former participants from the Miami and San Francisco sites of the US PrEP Demo Project, administered 4-6 months after study completion. RESULTS: Survey respondents continued to frequently access medical care and had a high incidence of sexually transmitted infections after completion of the Demo Project, indicating ongoing sexual risk behavior. Interest in continuing PrEP was high with 70.8% indicating that they were "very interested" in continuing PrEP. Among respondents, 39.9% reported continuation of PrEP after completion of the Demo Project, largely through their primary care providers and frequently at low or no cost. Variability in access and engagement was seen, with participants from the San Francisco site, those with medical insurance, and those with a primary care provider at the end of the Demo Project more likely to successfully obtain PrEP medication. Two respondents reported HIV seroconversion in the period between study completion and the follow-up survey. CONCLUSIONS: Additional effort to increase equitable access to PrEP outside of demonstration projects is needed to realize the potential impact of this evidence-based prevention intervention.