Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

BackgroundAlthough prison provides the opportunity for HIV diagnosis and access to in-prison care, following release, many HIV-infected inmates experience clinical setbacks, including nonadherence to antiretrovirals, elevations in viral load, and HIV disease progression. HIV-infected former inmates face numerous barriers to successful community reentry and to accessing healthcare. However, little is known about the outcome expectations of HIV-infected inmates for release, how their post-release lives align with pre-release expectations, and how these processes influence engagement in HIV care following release from prison.MethodsWe conducted semi-structured interviews (24 pre- and 13 post-release) with HIV-infected inmates enrolled in a randomized controlled trial of a case management intervention to enhance post-release linkage to care. Two researchers independently coded data using a common codebook. Intercoder reliability was strong (kappa = 0.86). We analyzed data using Grounded Theory methodology and Applied Thematic Analysis. We collected and compared baseline sociodemographic and behavioral characteristics of all cohort participants who did and did not participate in the qualitative interviews using Fisher’s Exact Tests for categorical measures and Wilcoxon rank-sum tests for continuous measures.ResultsMost participants were heterosexual, middle-aged, single, African American men and women with histories of substance use. Substudy participants were more likely to anticipate living with family/friends and needing income assistance post-release. Most were taking antiretrovirals prior to release and anticipated needing help securing health benefits and medications post-release. Before release, most participants felt confident they would be able to manage their HIV. However, upon release, many experienced intermittent or prolonged periods of antiretroviral nonadherence, largely due to substance use relapse or delays in care initiation. Substance use was precipitated by stressful life experiences, including stigma, and contact with drug-using social networks. As informed by the Social Cognitive Theory and HIV Stigma Framework, findings illustrate the reciprocal relationships among substance use, experiences of stigma, pre- and post-release environments, and skills needed to engage in HIV care.ConclusionThese findings underscore the need for comprehensive evidence-based interventions to prepare inmates to transition from incarceration to freedom, particularly those that strengthen linkage to HIV care and focus on realities of reentry, including stigma, meeting basic needs, preventing substance abuse, and identifying community resources.

Background Advances in antiretroviral therapy, aging, and comorbidities impact hospitalization rates in HIV-infected populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes. Methods Study population included patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving clinical care 1996–2016. We estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine and Gray, and log-binomial regression models. Results 4323 patients (29% women, 60% African-American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI] 32.4, 36.4) with a mean change of -3% per year (95% CI -4%, -2%). Thirty-day readmission risk was 18.9% (95% CI 17.7%, 20.2%) and stable over time (P=0.21 and P=0.44 for 2010–2016 and 2003–2009, respectively, compared to 1996–2002). Patients who were Black (compared to White), older, had HIV RNA >400 copies/mL, or had CD4 count <200 cells/µL had higher hospitalization rates (all P<0.05). Higher inpatient mortality was associated with older age and lower CD4 (both P<0.05). Thirty-day readmission risk was higher among Black patients, those with detectable HIV RNA, and with lower CD4 cell counts (all P<0.05). Conclusions Hospitalization rates decreased from 1996 to 2016, but readmissions remained unchanged and high. Older patients, of minority race/ethnicity, and with uncontrolled HIV experienced higher rates and worse hospitalization outcomes. These findings underscore the importance of early diagnosis and treatment, linkage and retention in care, and care engagement at the time of hospital discharge.

Studies establishing that intermittent subcutaneous interleukin-2 (IL-2) therapy can lead to substantial CD4 cell increases in many HIV-infected patients have generally been of limited duration. We studied 77 patients participating in active longitudinal studies of subcutaneous IL-2 therapy at our center in order to determine the long-term feasibility of this approach. Following initial induction, patients in each trial were eligible to receive intermittent 5-day cycles of subcutaneous IL-2 treatment at individualized doses and frequencies capable of maintaining CD4 counts at postinduction levels. The mean duration of study participation to date is 5.9 years (range, 1.0-9.3 years). Mean baseline CD4 cell count and CD4 percent values of 0.521 ؋ 10 9 /L (521 cells/ L) and 27% have risen to 1.005 ؋ 10 9 /L (1005 cells/L) and 38%, respectively, at 90 months. The mean number of subcutaneous IL-2 cycles required to achieve and maintain these increases was 10 cycles (range, 3-29 cycles), and the current mean interval of cycling required to maintain these elevations is 39 months (median, 35 months; range, 2-91 months). We conclude that subcutaneous IL-2 therapy is capable of maintaining CD4 cell increases for an extended period using a remarkably low frequency of intermittent cycling. These observations may contribute to patients' acceptance of subcutaneous IL-2 as a favorable long-term treatment strategy. (Blood. 2004;103:3282-3286)

Objectives:To determine what information is most important to registered nurses' (RNs) decisions to call clinicians about suspected urinary tract infections (UTIs) in nursing home residents. Design: Web-based discrete choice experiment with 19 clinical scenarios. Setting and Participants: Online survey with a convenience sample of RNs (N ¼ 881) recruited from a health care research panel. Methods: Clinical scenarios used information from 10 categories of resident characteristics: UTI risk, resident type, functional status, mental status, lower urinary tract status, body temperature, physical examination, urinalysis, antibiotic request, and goals of care. Participants were randomized into 2 deliberation conditions (self-paced, n ¼ 437 and forced deliberation, n ¼ 444). The degree to which evidence-and noneevidence-based information was important to decision-making was estimated using unconditional multinomial logistic regression. Results: For all nurses (22.8%) and the self-paced group (24.1%), lower urinary tract status had the highest importance scores for the decision to call a clinician about a suspected UTI. For the forced-deliberation group, body temperature was most important (23.7%), and lower urinary tract status was less important (21%, P ¼.001). The information associated with the highest odds of an RN calling about a suspected UTI was painful or difficult urination [odds ratio (OR) 4.85, 95% confidence interval (CI) 4.16e5.65], obvious blood in urine (OR 4.66, 95% CI 3.99e5.44), and temperature at 101.5 (OR 3.80, 95% CI 3.28e4.42). For the self-paced group, painful or difficult urination (OR 5.65, 95% CI 4.53e7.04) had the highest odds, whereas obvious blood in urine (OR 4.39, 95% CI 3.53e5.47) had highest odds for the forced-deliberation group. Conclusions and Implications: This study highlighted the importance of specific resident characteristics in nurse decision-making about suspected UTIs. Future antimicrobial stewardship efforts should aim to not only improve the previously studied overprescribing practices of clinicians, but to improve nurses' assessment of signs and symptoms of potential infections and how they weigh resident information.

Antiretroviral (ARV) adherence has largely been considered from the perspective of an individual's behavior with less attention given to potential structural causes for lapses in treatment, such as the cost of medications and care. HIV medication expense is typically covered by third party payers. However, private insurance premiums and deductibles may rise, or policies terminated such as with a change in employment. Likewise, a patient's eligibility for publicly funded coverage like state AIDS Drug Assistance Programs (ADAP) or Medicaid can also be lost. We conducted a one-time survey of a sample of 300 patients receiving HIV care at a single large academic center in the south of United States to examine lapses in HIV therapy due to financial reasons. We found that during the prior year, financial issues including medication cost or coverage led to a lapse in ARVs in 10% (n = 31) of participants. However, of the 42% (n = 125) participants who had been enrolled in ADAP at any time during the prior year, 21% (n = 26) reported an ARV lapse due to problems with ADAP or medication cost. Respondents cited ADAP's required semi-annual renewal process and other administrative issues as the cause of ARV lapses. The median duration of missed ARVs was 2 weeks (range of <1-23 weeks). Non-HIV medication and transportation to and from clinic costs were also identified as financial burdens to care by respondents. In conclusion, although conducted at a single medical center and one state, this study suggests that a significant minority of HIV-infected patients encounter financial barriers to ARV access, and this is paradoxically more common among those enrolled in the state ADAP. Streamlining, supporting, and simplifying ADAP renewal procedures will likely reduce lapses in ARV adherence and persistence.

Objective: To determine which nursing home (NH) resident characteristics were most important to clinicians' decision to prescribe antibiotics for a suspected urinary tract infection (UTI), including both evidence-based and non-evidence-based characteristics. Design: Web-based discrete choice experiment with 19 clinical scenarios. For each scenario, clinicians were asked whether they would prescribe an antibiotic for a suspected UTI. Setting: Online survey. Participants: Convenience sample of 876 NH physicians and advanced practice providers who practiced primary care for NH residents in the United States. Methods: Each scenario varied information about 10 resident characteristics regarding urinalysis results, resident temperature, lower urinary tract symptoms, physical examination, antibiotic request, mental status, UTI risk, functional status, goals of care, and resident type. We derived importance scores for the characteristics and odds ratios (ORs) for specific information related to each characteristic from a multinomial logistic regression.Results: Approximately half of the participants were male (56%) with a mean age of 49 years. Resident characteristics differed in their importance (ie, part-worth utility) when deciding whether to prescribe for a suspected UTI: urinalysis results (32%), body temperature (17%), lower urinary tract symptoms (17%), physical examination (15%), antibiotic request (7%), mental status (4%), UTI risk (4%), functional status (3%), goals of care (2%), and resident type (1%). Information about "positive leukocyte esterase, positive nitrates" was associated with highest odds of prescribing [OR 19.6, 95% confidence interval (CI) 16.9, 22.7], followed by "positive leukocyte esterase, negative nitrates" (OR 6.7, 95% CI 5.8, 7.6), and "painful or difficult urination" (OR 4.8, 95% CI 4.2, 5.5). Conclusions and Implications: Although guidelines focus on lower urinary tract symptoms, body temperature, and physical examination for diagnosing a UTI requiring antibiotics, these characteristics were considered less important than urinalysis results, which have inconsistent clinical utility in NH residents. Point-of-care clinical decision support offers an evidence-based prescribing process.

Correctional facilities offer opportunities to provide comprehensive HIV services including education, testing, treatment, and coordination of post-release care. However, these services may be undermined by unaddressed HIV stigma. As part of a prison-based HIV testing study, we interviewed 76 incarcerated men and women from the North Carolina State prison system. The sample was 72% men, median age 31.5 years (range: 19 to 60). Thematic analysis revealed high levels of HIV-related fear and stigma, homophobia, incomplete HIV transmission knowledge, beliefs that HIV is highly contagious within prisons (“HIV miasma”), and the view of HIV testing as protective. Interviewees described social distancing behaviors and coping mechanisms they perceived to be protective, including knowing their HIV status and avoiding contact with others and shared objects. Interviewees endorsed universal testing, public HIV status disclosure, and segregation of HIV-positive inmates. Intensified education and counseling efforts are needed to ameliorate entrenched HIV-transmission fears and stigmatizing beliefs.