Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study.

Pharmacologic inhibition of the mammalian target of rapamycin (mTOR) in the setting of renal transplantation has previously been associated with lower human immunodeficiency virus 1 (HIV-1) DNA burden, and in vitro studies suggest that mTOR inhibition may lead to HIV transcriptional silencing. Because prospective clinical trials are lacking, we conducted an open-label, single-arm study to determine the impact of the broad mTOR inhibitor, everolimus, on residual HIV burden, transcriptional gene expression profiles, and immune responses in HIV-infected adult solid organ transplant (SOT) recipients on antiretroviral therapy. Whereas everolimus therapy did not have an overall effect on cell-associated HIV-1 DNA and RNA levels in the entire cohort, participants who maintained everolimus time-averaged trough levels >5 ng/mL during the first 2 months of therapy had significantly lower RNA levels up to 6 months after the cessation of study drug. Time-averaged everolimus trough levels significantly correlated with greater inhibition of mTOR gene pathway transcriptional activity. Everolimus treatment also led to decreased PD-1 expression on certain T cell subsets. These data support the rationale for further study of the effects of mTOR inhibition on HIV transcriptional silencing in non-SOT populations, either alone or in combination with other strategies. Trial Registration: ClinicalTrials.gov NCT02429869.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

A comparative effectiveness education trial for lifestyle health behavior change in African Americans.

Obesity and excess weight are significant clinical and public health issues that disproportionately affect African Americans because of physical inactivity and unhealthy eating. We compared the effects of alternate behavioral interventions on obesity-related health behaviors. We conducted a comparative effectiveness education trial in a community-based sample of 530 adult African Americans. Outcomes variables were physical activity (PA) and fruit and vegetable intake. Outcomes were evaluated at baseline and 1-month following interventions about shared risk factors for cancer and cardiovascular disease (CVD) (integrated, INT) or CVD only (disease-specific). Significant increases were found in the proportion of participants who met PA guidelines from baseline (47.4%) to follow-up (52.4%) (P = 0.005). In the stratified analysis that were conducted to examine interaction between education and intervention group assignment, this effect was most apparent among participants who had ≤high school education and were randomized to INT (OR = 2.28, 95% CI = 1.04, 5.00, P = 0.04). Completing the intervention was associated with a 1.78 odds of meeting PA guidelines (95% CI = 1.02, 3.10, P = 0.04). Education about risk factors for chronic disease and evidence-based strategies for health behavior change may be useful for addressing obesity-related behaviors among African Americans.

Acceptance of a community-based navigator program for cancer control among urban African Americans.

Patient navigation is now a standard component of cancer care in many oncology facilities, but a fundamental question for navigator programs, especially in medically underserved populations, is whether or not individuals will use this service. In this study, we evaluated acceptance of a community-based navigator program for cancer control and identified factors having significant independent associations with navigation acceptance in an urban sample of African Americans. Participants were African American men and women ages 50-75 who were residents in an urban metropolitan city who were referred for navigation. Of 240 participants, 76% completed navigation. Age and perceived risk of developing cancer had a significant independent association with navigation acceptance. Participants who believed that they were at high risk for developing cancer had a lower likelihood of completing navigation compared with those who believed that they had a low risk for developing this disease. The likelihood of completing navigation increased with increases in age. None of the socioeconomic factors or health care variables had a significant association with navigation acceptance. There are few barriers to using community-based navigation for cancer control among urban African Americans. Continued efforts are needed to develop and implement community-based programs for cancer control that are easy to use and address the needs of medically underserved populations.

Collective efficacy and obesity-related health behaviors in a community sample of African Americans.

The social environment is important to body mass index and obesity. However, it is unknown if perceptions of the social environment are associated with obesity-related behaviors in populations at greatest risk for being overweight or obese. We evaluated the relationship between collective efficacy and diet and physical activity in a community-based sample of African American adults who were residents in an urban area. Data were collected as part of an academic-community partnership from November 2009 to 2011. We evaluated whether participants met the recommended guidelines for diet and physical activity based on collective efficacy and their sociodemographic background, health care variables, and self-efficacy in a community-based sample of African American adults (n = 338) who were residents in the Philadelphia, PA metropolitan area. Overall, many participants did not meet the recommended guidelines for fruit and vegetable intake or physical activity. The likelihood of meeting the recommended guidelines for fruit intake increased with greater levels of collective efficacy (OR 1.56, 95 % CI 1.18, 2.07, p = 0.002) and self-efficacy for diet (OR 1.56, 95 % CI 1.19, 2.04, p = 0.001). Collective efficacy was not associated with physical activity and the positive association between collective efficacy and vegetable intake was not statistically significant (OR 1.25, 95 % CI 0.94, 1.65, p = 0.12). It is important to determine the most effective methods and settings for improving diet and physical activity behaviors in urban African Americans. Enhancing collective efficacy may be important to improving adherence to recommended guidelines for obesity-related health behaviors.

Long-term Outcomes Following Kidney and Liver Transplant in Recipients With HIV.

Importance: Kidney transplant (KT) and liver transplant (LT) in HIV-positive patients have become more widely adopted. Data looking at long-term outcomes of patient and graft survival are lacking. Objective: To compare the long-term outcomes of KT and LT in HIV-positive recipients with matched HIV-negative recipients. Design, Setting, and Participants: Retrospective, single-center, cohort, study using data from 2000 to 2019. Patients were observed until death, or graft failure requiring retransplant. All HIV-positive patients who underwent KT and/or LT between 2000 and 2019 were included. Propensity matching was performed to the corresponding HIV-negative cohort, which was obtained from the University of California, San Francisco's transplant recipient registry. The data were analyzed from 2020 to 2021. Exposures: HIV infection. Main Outcomes and Measures: Patient and graft survival for KT and patient survival for LT. Incidence of acute rejection and its association with KT graft survival. Results: For KT, 655 HIV-negative recipients (mean [SD] age, 52.3 [13.6] years; 450 [68.7%] were men) and 119 HIV-positive recipients (mean [SD] age, 51.7 [9.4] years; 86 [72.3%] were men) were included. Patient survival was 79.6% (95% CI, 73.6%-86.1%) and 53.6% (95% CI, 38.9%-74.0%) at 15 years posttransplant, respectively. Graft survival was 57.0% (95% CI, 47.8%-68.0%) and 75.0% (95% CI, 65.3%-86.2%) at 15 years posttransplant, respectively. Diagnosis of HIV was not associated with worse graft survival (hazard ratio, 1.09; 95% CI, 0.61-1.97; P = .77). For LT, 80 HIV-positive recipients (mean [SD] age, 52.6 [8.2] years; 53 [66.3%] were men) and 440 HIV-negative recipients (mean [SD] age, 54.6 [12.8] years; 291 [66.1%] were men) were included. Patient survival was 75.7% (95% CI, 71.8%-79.8%) for HIV-negative LT recipients and 70.0% (95% CI, 60.6%-80.8%) for HIV-positive LT recipients at 15 years posttransplant. Diagnosis of HIV was not a statistically significant predictor of patient survival (hazard ratio, 1.36; 95% CI, 0.83-2.24; P = .22). In KT, HIV-positive patients with at least 1 episode of acute rejection had a graft survival of 52.8% (95% CI, 38.4%-72.5%; P < .001) at 15 years posttransplant, compared with 91.8% in those without AR. Conclusions and Relevance: In this single-center cohort study, KT and LT in HIV-positive patients had comparable long-term outcomes with those in matched HIV-negative patients. The high incidence of acute rejection was associated with reduced graft survival. The findings support providing transplant to HIV-positive patients, which may be an appropriate use of transplant resources and provides equitable access for HIV-positive patients.

Using a mixed-methods approach to identify health concerns in an African American community.

OBJECTIVES: We used qualitative and quantitative data collection methods to identify the health concerns of African American residents in an urban community and analyzed the extent to which there were consistencies across methods in the concerns identified. METHODS: We completed 9 focus groups with 51 residents, 27 key informant interviews, and 201 community health surveys with a random sample of community residents to identify the health issues participants considered of greatest importance. We then compared the issues identified through these methods. RESULTS: Focus group participants and key informants gave priority to cancer and cardiovascular diseases, but most respondents in the community health survey indicated that sexually transmitted diseases, substance abuse, and obesity were conditions in need of intervention. How respondents ranked their concerns varied in the qualitative versus the quantitative methods. CONCLUSIONS: Using qualitative and quantitative approaches simultaneously is useful in determining community health concerns. Although quantitative approaches yield concrete evidence of community needs, qualitative approaches provide a context for how these issues can be addressed. Researchers should develop creative ways to address multiple issues that arise when using a mixed-methods approach.

Participation rates and representativeness of African Americans recruited to a health promotion program.

When using community-based participatory methods to develop health promotion programs for specific communities, it is important to determine if participation differs based on sociodemographics and the extent to which program participants are demographically representative of the target community, especially when non-random recruitment methods are used. We evaluated rates of participating in a health promotion program among African American residents in an urban community and determined if program participants were representative of community residents in terms of sociodemographic factors. While participation in the program was modest, participation did not differ based on psychological factors or body mass index. However, individuals who were unemployed were significantly more likely to participate in the program compared with those who were employed. Our sample included a greater proportion of individuals who only had a high school education compared with community residents but was similar to community residents in terms of gender, marital status and employment.

Effects of integrated risk counseling for cancer and cardiovascular disease in African Americans.

OBJECTIVE: We evaluated a risk counseling intervention designed to enhance understanding about risk factors for cancer and cardiovascular disease, to improve self-efficacy for diet and physical activity, and to increase intentions to eat healthier and be physically active. METHODS: We conducted a quasi-experimental study developed by academic investigators and community stakeholders to evaluate the effects of integrated risk counseling in a community-based sample of African American adults (n = 101). The intervention provided education about the overlap in risk factors for cancer and cardiovascular disease and included components from motivational interviewing. RESULTS: Changes in behavioral intentions were not statistically significant (p > .05). Participants reported significantly greater levels of self-efficacy for diet (t = 2.25, p = .03) and physical activity (t = 2.55, p = .01), and significantly increased perceived risks of developing colon cancer (chi2 = 3.86, p = .05) and having a heart attack (chi2 = 4.50, p = .03). CONCLUSIONS: Integrated risk counseling may have some benefits among African Americans.

Immunologic Predictors of Liver Transplantation Outcomes in HIV-HCV Co-Infected Persons.

Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210-429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7-4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02-0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01-4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.

Intervention completion rates among African Americans in a randomized effectiveness trial for diet and physical activity changes.

BACKGROUND: The intervention completion rate is an important metric in behavioral and intervention research; trials with limited intervention completion rates may have reduced internal validity. We examined intervention completion rates among 530 African Americans who had been randomized to an integrated (INT) or disease-specific (DSE) risk education protocol as part of a comparative effectiveness trial from September 2009 to August 2012. METHODS: The interventions were developed by an academic-community partnership using community-based participatory research. Intervention completion rates were determined based on attendance at all four intervention sessions. Intervention completers were participants who completed all four sessions and noncompleters were those who did not complete any session or only completed one to three sessions following randomization. RESULTS: Seventy-three percent of participants were intervention completers and 27% were noncompleters. There were no differences in intervention completion based on randomization to INT (72%) or DSE (75%), sociodemographic factors, or body mass index (BMI) in the total sample. Different factors were associated significantly with intervention completion within study groups. Among participants randomized to INT, the odds of intervention completion were greater with higher levels of intrinsic motivation, less exposure to information about diet and cardiovascular disease, and greater BMI. Among participants randomized to DSE, the odds of completing the intervention were associated significantly with older age and greater dietary self-efficacy. CONCLUSIONS: Many African Americans are likely to complete risk education interventions. IMPACT: Psychologic characteristics should be considered when determining intervention completion rates following randomization in behavioral and intervention trials.