Accurate predictions of population-level changes in sequence and structural properties of HIV-1 Env using a volatility-controlled diffusion model.

The envelope glycoproteins (Envs) of HIV-1 continuously evolve in the host by random mutations and recombination events. The resulting diversity of Env variants circulating in the population and their continuing diversification process limit the efficacy of AIDS vaccines. We examined the historic changes in Env sequence and structural features (measured by integrity of epitopes on the Env trimer) in a geographically defined population in the United States. As expected, many Env features were relatively conserved during the 1980s. From this state, some features diversified whereas others remained conserved across the years. We sought to identify "clues" to predict the observed historic diversification patterns. Comparison of viruses that cocirculate in patients at any given time revealed that each feature of Env (sequence or structural) exists at a defined level of variance. The in-host variance of each feature is highly conserved among individuals but can vary between different HIV-1 clades. We designate this property "volatility" and apply it to model evolution of features as a linear diffusion process that progresses with increasing genetic distance. Volatilities of different features are highly correlated with their divergence in longitudinally monitored patients. Volatilities of features also correlate highly with their population-level diversification. Using volatility indices measured from a small number of patient samples, we accurately predict the population diversity that developed for each feature over the course of 30 years. Amino acid variants that evolved at key antigenic sites are also predicted well. Therefore, small "fluctuations" in feature values measured in isolated patient samples accurately describe their potential for population-level diversification. These tools will likely contribute to the design of population-targeted AIDS vaccines by effectively capturing the diversity of currently circulating strains and addressing properties of variants expected to appear in the future.

Washington state satellite HIV clinic program: a model for delivering highly effective decentralized care in under-resourced communities.

To improve access to high-quality HIV care in underserved regions of Western Washington (WA) State, we collaborated with the WA State Department of Health (DOH) and community partners to launch four satellite HIV clinics. Here, we describe this innovative clinical care model, present an estimate of costs, and evaluate patient care outcomes, including virologic suppression rates. To accomplish this, we assessed virologic suppression rates 12 months before and 12 months after the satellite clinics opened, comparing people living with HIV (PLWH) who enrolled in the satellite clinics versus all PLWH in the same regions who did not. We also determined virologic suppression rates in 2015 comparing satellite clinic versus non-satellite clinic patients and compared care quality indicators between the satellite clinics and the parent academic clinic. Results demonstrate that the change in virologic suppression rate 12 months before to 12 months after the satellite clinics opened was higher for patients who enrolled in the satellite clinics compared to all those in the same region who did not (18% versus 6%, p < 0.001). Virologic suppression in 2015 was significantly higher for satellite clinic than non-satellite clinic patients at three of four sites. Care quality indicators were met at a high level at the satellite clinics, comparable to the parent academic clinic. Overall, through community partnerships and WA DOH support, the satellite clinic program increased access to best practice HIV care and improved virologic suppression rates in difficult-to-reach areas. This model could be expanded to other regions with inadequate access to HIV practitioners, though financial support is necessary.

HIV Provider Documentation and Actions Following Patient Reports of At-risk Behaviors and Conditions When Identified by a Web-Based Point-of-Care Assessment.

We compared same-day provider medical record documentation and interventions addressing depression and risk behaviors before and after delivering point-of-care patient-reported outcomes (PROs) feedback for patients who self-reported clinically relevant levels of depression or risk behaviors. During the study period (1 January 2006-15 October 2010), 2289 PRO assessments were completed by HIV-infected patients. Comparing the 8 months before versus after feedback implementation, providers were more likely to document depression (74% before vs. 87% after feedback, p = 0.02) in patients with moderate-to-severe depression (n = 317 assessments), at-risk alcohol use (41 vs. 64%, p = 0.04, n = 155) and substance use (60 vs. 80%, p = 0.004, n = 212). Providers were less likely to incorrectly document good adherence among patients with inadequate adherence after feedback (42 vs. 24%, p = 0.02, n = 205). While PRO feedback of depression and adherence were followed by increased provider intervention, other domains were not. Further investigation of factors associated with the gap between awareness and intervention are needed in order to bridge this divide.

Evidence for the long-term stability of HIV transmission-associated sexual behavior after HIV diagnosis.

BACKGROUND: Most persons diagnosed as having HIV alter their sexual behavior in a way that reduces the risk of HIV transmission, but the durability of such behavior change is unknown. METHODS: We conducted annual anonymous cross-sectional surveys in randomly selected patients with appointments at a large, public hospital HIV clinic in Seattle, Washington, from 2005 to 2009. We used logistic regression to assess the association between time since HIV diagnosis and self-report of unprotected anal or vaginal intercourse (UAVI) with partners of negative or unknown HIV status (nonconcordant UAVI), and quantile regression to evaluate the association between time since HIV diagnosis and number of anal or vaginal sex partners. RESULTS: We analyzed 845 surveys collected for 5 years. Men who have sex with men (MSM) had been diagnosed as having HIV a mean (standard deviation) of 12 (7) years and non-MSM a mean of 11 (6) years. Among 597 MSM, longer time since HIV diagnosis was associated with lower age-adjusted odds of reporting nonconcordant UAVI (odds ratio, 0.96 [95% confidence interval, 0.92-0.99]) and a lower age-adjusted number of sex partners (ß coefficient = -0.03, P = 0.007). Among 248 women and heterosexual men, time since HIV diagnosis was not significantly associated with age-adjusted odds of nonconcordant UAVI (odds ratio 0.99 [95% confidence interval, 0.93-1.04]) or number of sex partners (ß coefficient = -0.01, P = 0.48). CONCLUSIONS: These results indicate that HIV transmission-associated behavior is relatively stable following the first year after HIV diagnosis. Our findings suggest that behavior change in the first year after HIV diagnosis, reported in other studies, is durable.

Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection.

BACKGROUND: The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs. METHODS: We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS-defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS. RESULTS: Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%-16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P < .01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4(+) cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53 cells/µL, P = .04, mucocutaneous KS; +261 vs +113, P = .04, tuberculosis). CONCLUSIONS: Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality.

PrPres in placental tissue following experimental transmission of atypical scrapie in ARR/ARR sheep is not infectious by Tg338 mouse bioassay.

Nor98-like atypical scrapie is a sporadic disease that affects the central nervous system of sheep and goats that, in contrast to classical scrapie, is not generally regarded as naturally transmissible. However, infectivity has been demonstrated via bioassay not only of brain tissue but also of certain peripheral nerves, lymphoid tissues, and muscle. This study examines placental tissue, a well characterized route of natural transmission for classical scrapie. Further, this study was conducted in sheep homozygous for the classical scrapie resistant ARR genotype and is the first to characterize the transmission of Nor98-like scrapie between homozygous-ARR sheep. Nor98-like scrapie isolated from a United States ARR/ARR sheep was transmitted to four ARR/ARR ewes via intracerebral inoculation of brain homogenate. These ewes were followed and observed to 8 years of age, remained non-clinical but exhibited progression of infection that was consistent with Nor98-like scrapie, including characteristic patterns of PrPSc accumulation in the brain and a lack of accumulation in peripheral lymphoid tissues as detected by conventional methods. Immunoblots of placental tissues from the infected ewes revealed accumulation of a distinct conformation of PrPres, particularly as the animals aged; however, the placenta showed no infectivity when analyzed via ovinized mouse bioassay. Taken together, these results support a low risk for natural transmission of Nor98-like scrapie in ARR/ARR sheep.

Stable HIV Reservoir Despite Prolonged Low-Dose Mycophenolate to Limit CD4+ T-cell Proliferation.

Background: The HIV reservoir of latently infected CD4+ T cells represents the barrier to cure. CD4+ T-cell proliferation is a mechanism that sustains the reservoir even during prolonged antiretroviral therapy (ART). Blocking proliferation may therefore deplete the reservoir. Methods: We conducted an unblinded, uncontrolled clinical trial of mycophenolate, a T-cell antiproliferative compound, in people with HIV on chronic suppressive ART. Study drug dose selection was based on calibration to an observed ex vivo antiproliferative effect. The primary outcome was clinically significant reduction (>0.25 log10) in the HIV reservoir, measured by total and intact HIV DNA per million T cells in blood over 48 weeks. Results: Five participants enrolled in the trial. Four participants took mycophenolate mofetil (MMF). One had a per-protocol switch to enteric-coated mycophenolate sodium (Myfortic) due to nausea but left the study for personal reasons. One participant developed finger cellulitis, but there were no opportunistic infections. In the 4 participants who completed the protocol, there was no clinically significant reduction in total or intact HIV DNA. There was no change in blood CD4+ T-cell subset composition within the HIV reservoir or the entire CD4+ T-cell population, although total CD4+ T cells decreased slightly in all 4 participants. An ex vivo antiproliferative effect was observed using participant serum obtained 1 hour after dosing, but this effect was severely diminished at drug trough. Conclusions: Mycophenolate given over 48 weeks did not reduce the volume or composition of the HIV reservoir. Clinical Trials registration: NCT03262441.

Correlates of 90-Day Mortality Among People Who Do and Do Not Inject Drugs With Infective Endocarditis in Seattle, Washington.

Background: Infective endocarditis (IE) remains highly morbid, but few studies have evaluated factors associated with IE mortality. We examined correlates of 90-day mortality among people who inject drugs (PWID) and people who do not inject drugs (non-PWID). Methods: We queried the electronic medical record for cases of IE among adults ≥18 years of age at 2 academic medical centers in Seattle, Washington, from 1 January 2014 to 31 July 2019. Cases were reviewed to confirm a diagnosis of IE and drug use status. Deaths were confirmed through the Washington State death index. Descriptive statistics were used to characterize IE in PWID and non-PWID. Kaplan-Meier log-rank tests and Cox proportional hazard models were used to assess correlates of 90-day mortality. Results: We identified 507 patients with IE, 213 (42%) of whom were PWID. Sixteen percent of patients died within 90 days of admission, including 14% of PWID and 17% of non-PWID (P = .50). In a multivariable Cox proportional hazard model, injection drug use was associated with a higher mortality within the first 14 days of admission (adjusted hazard ratio [aHR], 2.33 [95% confidence interval {CI}, 1.16-4.65], P = .02); however, there was no association between injection drug use and mortality between 15 and 90 days of admission (aHR, 0.63 [95% CI, .31-1.30], P = .21). Conclusions: Overall 90-day mortality did not differ between PWID and non-PWID with IE, although PWID experienced a higher risk of death within 14 days of admission. These findings suggest that early IE diagnosis and treatment among PWID is critical to improving outcomes.

Comparative Effectiveness and Toxicity of Statins Among HIV-Infected Patients.

BACKGROUND: dyslipidemia is common and is often treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Little is known about the comparative effectiveness of statins among human immunodeficiency virus (HIV)-infected patients. This study compared the effectiveness and toxicity of statins among HIV-infected patients in clinical care. METHODS: we conducted a retrospective cohort study of patients starting their initial statin medications at 2 large HIV clinics (N = 700). The primary observation was change in lipid levels during statin therapy. Secondary observations included whether individualized National Cholesterol Education Program (NCEP) goals for low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) levels were reached, and toxicity rates. We used linear regression to examine change in lipid levels, controlling for baseline lipid values and demographic and clinical characteristics. We conducted secondary analyses using propensity scores to address confounding by indication. RESULTS: the most commonly prescribed statins were atorvastatin (N = 303), pravastatin (N = 280), and rosuvastatin (N = 95). One year after starting a statin therapy, patients who received atorvastatin or rosuvastatin had significantly greater decreases in total cholesterol, LDL-C, and non-HDL-C than patients on pravastatin. The likelihood of reaching NCEP goals for LDL-C levels was higher with the use of rosuvastatin (OR 2.1; P = .03) and atorvastatin (odds ratio [OR], 2.1; P = .001) compared with that of pravastatin. The likelihood of reaching NCEP goals for non-HDL-C levels was higher for rosuvastatin (OR 2.3; P = .045) but not atorvastatin (OR, 1.5; P = .1) compared with pravastatin. Toxicity rates were similar for all 3 statins: 7.3% for atorvastatin, 6.1% for pravastatin, and 5.3% for rosuvastatin. CONCLUSIONS: our findings suggest that atorvastatin and rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients with dyslipidemia, due to greater declines in total cholesterol, LDL-C, and non-HDL-C, with similar lower toxicity rates.

Somatic symptoms and the association between hepatitis C infection and depression in HIV-infected patients.

Studies of depression and hepatitis C virus (HCV) infection in HIV-infected patients have been contradictory and often not addressed key differences between HCV-infected and uninfected individuals including substance use. This cross-sectional observational study from the University of Washington HIV cohort examined associations between HCV, symptoms, and depression in HIV-infected patients in routine clinical care. Patients completed instruments measuring depression, symptoms, and substance use. We generated depression severity scores and used linear regression to examine the relationship with HCV accounting for demographic and clinical characteristics. We conducted sensitivity analyses in which we removed depression somatic symptom items (e.g., fatigue) from depression scores, and sensitivity analyses in which we also adjusted for nondepression somatic symptom items to examine the role of somatic and nonsomatic symptoms in the association between depression and HCV. Of 764 HIV-infected patients, 160 (21%) were HCV-infected. In adjusted analysis, HCV-infected patients had worse depression severity (p =0.01) even after adjusting for differences in substance use. HCV remained associated with depression severity in secondary analyses that omitted the depression somatic patient health questionnaire-9 (PHQ-9) items (p=0.01). However, when nondepression somatic symptoms were included as covariates in multivariate analyses, HCV was no longer associated with depression (p=0.09).

Creating a Framework to Integrate Residency Program and Medical Center Approaches to Quality Improvement and Patient Safety Training.

Quality improvement and patient safety (QIPS) are core components of graduate medical education (GME). Training programs and affiliated medical centers must partner to create an environment in which trainees can learn while meaningfully contributing to QIPS efforts, to further the shared goal of improving patient care. Numerous challenges have been identified in the literature, including lack of resources, lack of faculty expertise, and siloed QIPS programs. In this article, the authors describe a framework for integrated QIPS training for residents in the University of Washington Internal Medicine Residency Program, beginning in 2014 with the creation of a dedicated QIPS chief resident position and assistant program director for health systems position, the building of a formal curriculum, and integration with medical center QIPS efforts. The postgraduate year (PGY) 1 curriculum focused on the culture of patient safety and entering traditional patient safety event (PSE) reports. The PGY-2 curriculum highlighted QIPS methodology and how to conduct mentored PSE reviews of cases that were of educational value to trainees and a clinical priority to the medical center. Additional PGY-2/PGY-3 training focused on the active report, presentation, and evaluation of cases during morbidity and mortality conferences while on clinical services, as well as how to lead longitudinal QIPS work. Select residents led mentored QI projects as part of an additional elective. The hallmark feature of this framework was the depth of integration with medical center priorities, which maximized educational and operational value. Evaluation of the program demonstrated improved attitudes, knowledge, and behavior changes in trainees, and significant contributions to medical center QIPS work. This specialty-agnostic framework allowed for training program and medical center integration, as well as horizontal integration across GME specialties, and can be a model for other institutions.

Generation of HIV-1-specific CD8+ cell responses following allogeneic hematopoietic cell transplantation.

This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1-specific CD8(+) cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8(+) T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1-specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).

Electronic Consults for Infectious Diseases in a United States Multisite Academic Health System.

We launched Infectious Disease electronic consultations (eConsults) in 2018. During the first 15.5 months, primary care practitioners submitted 328 eConsults; the most frequent reasons were a positive culture or polymerase chain reaction (PCR) result, syphilis, and latent tuberculosis. Practitioners commonly requested advice on antimicrobial choice, clinical evaluation, and indications for treatment. Internal phone consultations decreased after eConsult implementation.

Leaf: an open-source, model-agnostic, data-driven web application for cohort discovery and translational biomedical research.

OBJECTIVE: Academic medical centers and health systems are increasingly challenged with supporting appropriate secondary use of clinical data. Enterprise data warehouses have emerged as central resources for these data, but often require an informatician to extract meaningful information, limiting direct access by end users. To overcome this challenge, we have developed Leaf, a lightweight self-service web application for querying clinical data from heterogeneous data models and sources. MATERIALS AND METHODS: Leaf utilizes a flexible biomedical concept system to define hierarchical concepts and ontologies. Each Leaf concept contains both textual representations and SQL query building blocks, exposed by a simple drag-and-drop user interface. Leaf generates abstract syntax trees which are compiled into dynamic SQL queries. RESULTS: Leaf is a successful production-supported tool at the University of Washington, which hosts a central Leaf instance querying an enterprise data warehouse with over 300 active users. Through the support of UW Medicine (https://uwmedicine.org), the Institute of Translational Health Sciences (https://www.iths.org), and the National Center for Data to Health (https://ctsa.ncats.nih.gov/cd2h/), Leaf source code has been released into the public domain at https://github.com/uwrit/leaf. DISCUSSION: Leaf allows the querying of single or multiple clinical databases simultaneously, even those of different data models. This enables fast installation without costly extraction or duplication. CONCLUSIONS: Leaf differs from existing cohort discovery tools because it does not specify a required data model and is designed to seamlessly leverage existing user authentication systems and clinical databases in situ. We believe Leaf to be useful for health system analytics, clinical research data warehouses, precision medicine biobanks, and clinical studies involving large patient cohorts.

Optimal timing of routine vaccination in HIV-infected persons.

Vaccine recommendations for those with HIV require continual updating as additional research becomes available. Timing of vaccinations among HIV-infected individuals is a key area of uncertainty. This is particularly true for those who may soon initiate highly active antiretroviral therapy (HAART) because immune reconstitution due to HAART often improves responses to vaccines. However, risks of delaying vaccination include that the patient may be exposed to the pathogen or lost to follow-up before vaccination. We review recent studies on the timing of routine vaccination of HIV-infected individuals.

Ovine progressive pneumonia provirus levels are unaffected by the prion 171R allele in an Idaho sheep flock.

Selective breeding of sheep for arginine (R) at prion gene (PRNP) codon 171 confers resistance to classical scrapie. However, other effects of 171R selection are uncertain. Ovine progressive pneumonia/Maedi-Visna virus (OPPV) may infect up to 66% of a flock thus any affect of 171R selection on OPPV susceptibility or disease progression could have major impact on the sheep industry. Hypotheses that the PRNP 171R allele is 1) associated with the presence of OPPV provirus and 2) associated with higher provirus levels were tested in an Idaho ewe flock. OPPV provirus was found in 226 of 358 ewes by quantitative PCR. The frequency of ewes with detectable provirus did not differ significantly among the 171QQ, 171QR, and 171RR genotypes (p > 0.05). Also, OPPV provirus levels in infected ewes were not significantly different among codon 171 genotypes (p > 0.05). These results show that, in the flock examined, the presence of OPPV provirus and provirus levels are not related to the PRNP 171R allele. Therefore, a genetic approach to scrapie control is not expected to increase or decrease the number of OPPV infected sheep or the progression of disease. This study provides further support to the adoption of PRNP 171R selection as a scrapie control measure.

Dalbavancin as Secondary Therapy for Serious Staphylococcus aureus Infections in a Vulnerable Patient Population.

We retrospectively evaluated off-label use of dalbavancin as secondary therapy in 32 patients with serious Staphylococcus aureus infections (endocarditis, osteomyelitis, septic thrombophlebitis, epidural infection) who were also persons who use drugs. The majority of patients (56%) had a clinical response to treatment. Only 1 patient who completed the intended dalbavancin course experienced a treatment failure.

HIV Care for Patients With Complex Needs: A Controlled Evaluation of a Walk-In, Incentivized Care Model.

BACKGROUND: New approaches are needed to provide care to persons with HIV who do not engage in conventionally organized HIV clinics. The Max Clinic in Seattle, Washington, is a walk-in, incentivized HIV care model located in a public health STD clinic that provides care in collaboration with a comprehensive HIV primary care clinic (the Madison Clinic). METHODS: We compared outcomes in the first 50 patients enrolled in Max Clinic and 100 randomly selected matched Madison Clinic control patients; patients in both groups were virally unsuppressed (viral load [VL] >200 copies/mL) at baseline. The primary outcome was any VL indicating viral suppression (≥1 VL <200 copies/mL) during the 12 months postbaseline. Secondary outcomes were continuous viral suppression (≥2 consecutive suppressed VLs ≥60 days apart) and engagement in care (≥2 medical visits ≥60 days apart). We compared outcomes in the 12 months pre- and postbaseline and used generalized estimating equations to compare changes in Max vs control patients, adjusting for unstable housing, substance use, and psychiatric disorders. RESULTS: Viral suppression improved in both groups pre-to-post (20% to 82% Max patients; P < .001; and 51% to 65% controls; P = .04), with a larger improvement in Max patients (adjusted relative risk ratio [aRRR], 3.2; 95% confidence interval [CI], 1.8-5.9). Continuous viral suppression and engagement in care increased in both groups but did not differ significantly (continuous viral suppression: aRRR, 1.5; 95% CI, 0.5-5.2; engagement: aRRR, 1.3; 95% CI, 0.9-1.9). CONCLUSIONS: The Max Clinic improved viral suppression among patients with complex medical and social needs.

Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons.

Protective response rates to hepatitis B (HB) vaccination have been reported as low as 18-62% in HIV-infected persons. The relative importance of various predictors for this poor response has not been fully characterized. In this retrospective cohort study, we examined the relationship between clinical characteristics and vaccine non-response (HB surface antibody <10 IU/L) among patients attending an urban HIV clinic. Among the 97 patients who met the inclusion criteria, 43 (44%) developed a protective antibody response. In multivariate analyses, age >40 years (odds ratio [OR] 3.03 [95% confidence interval [CI], 1.14-8.06]; P = 0.026) and alcohol abuse (OR 4.92 [95% CI, 1.72-20.89]; P = 0.007) were independent predictors of failure to develop vaccine response. In addition, CD4 nadir <200 (OR 7.24 [95% CI, 1.91-27.41]; P = 0.004), rather than CD4 current to vaccination, remained a strong independent risk factor. Patients with HIV viral suppression on highly active antiretroviral therapy had a significantly lower rate of vaccine failure (OR 0.31 [95% CI, 0.11-0.91]; P = 0.033), after adjusting for these other covariates. Our findings underscore the importance of confirming seroconversion after HB vaccination in HIV-infected patients and initiating vaccination early in the course of HIV infection.

The Max Clinic: Medical Care Designed to Engage the Hardest-to-Reach Persons Living with HIV in Seattle and King County, Washington.

The Max Clinic in Seattle, Washington is designed to engage patients who have extensive barriers to HIV care. In this article, we describe the clinic's evolution and outcomes of patients enrolled in the first 2 years. The clinic is a high-intensity, low-threshold, incentivized care model that includes walk-in access to primary care in a Sexually Transmitted Disease Clinic. Patients who have failed to engage in care and achieve viral suppression with lower intensity support are referred by clinicians, case managers, and the health department Data to Care program. The clinic offers food vouchers, cash incentives, no-cost bus passes, and cell phones, as well as intensive case management with cross-agency coordinated care. The primary evaluation outcome was the percentage of patients who achieved viral suppression (HIV RNA <200 copies/mL) at least once after enrollment. Secondary outcomes were continuous viral suppression (≥2 suppressed results in a row ≥60 days apart) and engagement in care (≥2 completed medical visits ≥60 days apart). During January 2015-December 2016, 263 patients were referred; 170 (65%) were eligible, and 95 (56% of eligible) were enrolled. Most patients used illicit drugs or hazardous levels of alcohol (86%) and had diagnosed psychiatric illness (72%) and unstable housing (65%). During the year after enrollment, 90 (95%) patients engaged in care. As of the end of 2016, 76 (80%) had achieved viral suppression, and 54% had continuous viral suppression. The Max Clinic successfully treated HIV in high-need patients and, to date, has been sustainable through a combination of federal, state, and local funding.