Syndemic factors associated with adherence to antiretroviral therapy among HIV-positive adult heterosexual men

Background Suboptimal adherence to HIV antiretroviral therapy (ART) and concomitant lack of viral control can have severe consequences for health and onward transmission among persons living with HIV. Little is known about the barriers and facilitators of optimal ART adherence among heterosexual HIV-positive men. Methods Structural equation modeling (SEM) was performed to test a theory-derived model of ART adherence using data from a cross-sectional sample of 317 HIV-positive self-identified heterosexual men residing in New York City. We assessed a conceptual model in which mental health (depression, anxiety) and substance use dependence mediated the effects of socio-structural factors (HIV-related stigma, social support) on ART adherence, and subsequently, undetectable viral load. Results Structural equation modeling analyses indicated that men who reported higher levels of HIV-related stigma tended to experience higher levels of general anxiety, which in turn was associated with reduced probability of optimal ART adherence. Moreover, men who reported higher levels of social support tended to exhibit less dependence on illicit substance use, which in turn was associated with increased probability of optimal ART adherence. African-American men reported lower ART adherence compared to other racial/ethnic groups. Conclusions Our findings support the hypothesis that substance use dependence and mental health problems, particularly anxiety, may be primary drivers of suboptimal ART adherence among heterosexual men, and that socio-structural factors such as HIV-related stigma and social support are potential modifiable antecedents of these drivers

Associations between Home- and School-Based Violent Experiences and the Development of Sexual Behavior in Young Adolescent Girls in the Rural Southern Region of Malawi

Studies show that adolescent girls who experience violence grow up with fear and develop survival mechanisms that increase their susceptibility to sexually transmitted infections including HIV. However, the relationship between violence and the development of sexual behavior in young adolescent girls is under-investigated. We examined the Malawi Schooling and Adolescent Study data to explore the associations between home- and school-based violence and sexual behaviors in 416 young adolescent girls in rural Southern Malawi. Bivariate Logistic Regression analysis was applied to determine associations. Of 353 (84.9%) girls who had sex with a male partner, 123 (34.8%) experienced home-based violence, and 53 (15%) experienced school-based violence. The odds of girls who experienced home-based violence (OR = 2.46, 95% CI = 1.21, 5.01) and those who first experienced home-based violence between 13 and 14 years (OR = 2.78, 95% CI = 1.35, 5.74) were higher among girls who had multiple sexual partners than those with a single sexual partner. With school-based violence, sexual initiation, having multiple sexual partners, and not using protection were positively associated with experiencing teasing, sexual comments, punching, and touching in private areas in transit to school and by a teacher. These results suggest that home- and school-based violence should be essential components of research and biobehavioral interventions targeting the sexual behaviors of young adolescent girls

Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (\u3c0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models. Results The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P \u3c 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. Conclusion In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months. Copyright © 2013 by the American College of Rheumatology

Feasibility and safety of a 6-month exercise program to increase bone and muscle strength in children with juvenile idiopathic arthritis

Background: Arthritis in childhood can be associated with muscle weakness around affected joints, low bone mass and low bone strength. Exercise is recognized as an important part of management of children with juvenile idiopathic arthritis (JIA) but the exercise prescription to best promote bone and muscle health is unknown. We therefore aimed to: 1. assess feasibility and safety of a 6-month home- and group-based exercise program for children with JIA; 2. estimate the effect of program participation on bone mass and strength, muscle function and clinical outcomes and 3. determine if any positive changes in bone and muscle outcomes are maintained 6 months later. Methods: We recruited 24 children with JIA who were part of the Linking Exercise, Physical Activity and Pathophysiology in Childhood Arthritis (LEAP) study to participate in a 6-month home-based exercise program involving jumping and handgrip exercises, resistance training and one group exercise session per month. We assessed lumbar spine bone mass (dual energy X-ray absorptiometry), distal tibia and radius bone microarchitecture and strength (high-resolution peripheral quantitative computed tomography), muscle function (jumping mechanography, dynamometry) and clinical outcomes (joint assessment, function, health-related quality of life) at baseline, 6- and 12-months. Adherence was assessed using weekly activity logs. Results: Thirteen children completed the 6-month intervention. Participants reported 9 adverse events and post-exercise pain was rare (0.4%). Fatigue improved, but there were no other sustained improvements in muscle, bone or clinical outcomes. Adherence to the exercise program was low (47%) and decreased over time. Conclusion: Children with JIA safely participated in a home-based exercise program designed to enhance muscle and bone strength. Fatigue improved, which may in turn facilitate physical activity participation. Prescribed exercise posed adherence challenges and efforts are needed to address facilitators and barriers to participation in and adherence to exercise programs among children with JIA. Trial registration: Data of the children with JIA are from the LEAP study (Canadian Institutes of Health Research (CIHR; GRANT# 107535). http://www.leapjia.com/

Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial

BACKGROUND: New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs. We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma. METHODS: In this open-label, multicentre, phase 2 trial done in Canada, Spain, and the USA, patients (age ≥18 years) with multiple myeloma who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs, were randomly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study, to decide the dose for further assessment in part 2. Patients received 8 mg/kg every 4 weeks, or 16 mg/kg per week for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3-6), and then every 4 weeks thereafter (cycle 7 and higher). The allocation schedule was computer-generated and randomisation, with permuted blocks, was done centrally with an interactive web response system. In part 1 stage 2 and part 2, patients received 16 mg/kg dosed as in part 1 stage 1. The primary endpoint was overall response rate (partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the analysis. The trial is registered with ClinicalTrials.gov, number NCT01985126. FINDINGS: The study is ongoing. In part 1 stage 1 of the study, 18 patients were randomly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group. Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2. Patients received a median of five previous lines of therapy (range 2-14). 85 (80%) patients had previously received autologous stem cell transplantation, 101 (95%) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used, and 103 (97%) were refractory to the last line of therapy. Overall responses were noted in 31 patients (29.2%, 95% CI 20.8-38.9)-three (2.8%, 0.6-8.0) had a stringent CR, ten (9.4%, 4.6-16.7) had a very good PR, and 18 (17.0%, 10.4-25.5) had a PR. The median time to first response was 1.0 month (range 0.9-5.6). Median duration of response was 7.4 months (95% CI 5.5-not estimable) and progression-free survival was 3.7 months (95% CI 2.8-4.6). The 12-month overall survival was 64.8% (95% CI 51.2-75.5) and, at a subsequent cutoff, median overall survival was 17.5 months (95% CI 13.7-not estimable). Daratumumab was well tolerated; fatigue (42 [40%] patients) and anaemia (35 [33%]) of any grade were the most common adverse events. No drug-related adverse events led to treatment discontinuation. INTERPRETATION: Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma, with a favourable safety profile in this population of patients. FUNDING: Janssen Research & Development

The Magnetic Couples Study: Protocol for a Mixed Methods Prospective Cohort Study of HIV-serodifferent Heterosexual Couples’ Perspectives and Use of Pre-Exposure Prophylaxis (PrEP)

Introduction HIV transmission within serodifferent heterosexual couples plays a key role in sustaining the global HIV pandemic. In the USA, transmission within established mixed-status couples accounts for up to half of all new HIV infections among heterosexuals. Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective prevention method, although underutilised among serodifferent couples. Moreover, there is a dearth of research on US HIV-serodifferent couples’ perspectives and use of PrEP, alone or in combination with other prevention methods. In this paper, we describe the study protocol for the Magnetic Couples Study, designed to fill critical knowledge gaps regarding HIV-serodifferent heterosexual couples’ perspectives, experiences and utilisation of PrEP. Methods and analysisThe Magnetic Couples Study is a mixed methods prospective cohort study designed to describe temporal patterns and identify determinants at multiple levels (individual, couple, HCF) of PrEP outcomes along the care continuum (PrEP awareness, linkage, uptake, retention and medication adherence) among HIV-serodifferent heterosexual couples residing in New York City. The study will also examine clinical management of PrEP, side effects and changes in sexual-related and substance use–related behaviour. A prospective cohort of 230 mixed-status couples already on oral PrEP was recruited, with quarterly assessments over 18 months; in addition, a cross-sectional sample of 150 mixed-status couples not currently on PrEP was recruited. In-depth semistructured qualitative interviews were conducted with a subsample of 25 couples. Actor-partner interdependence modelling using multilevel analysis will be employed for the analysis of longitudinal dyadic data. Framework analysis will be used to analyse qualitative data. A parallel convergent design will be used for mixed methods integration. Ethics and dissemination The study was approved by the University of Rochester Institutional Review Board (RSRB00052766). Study findings will be disseminated to community members and providers and to researchers and policy makers

Providers' Perceptions of Couples' HIV Testing and Counseling (CHTC): Perspectives From a U.S. HIV Epicenter

Current epidemiology demonstrates the significance of couple-based HIV transmission among vulnerable U.S. populations and its contribution to health disparity in HIV prevalence. Couples' HIV testing and counseling (CHTC) can be used to address couple-based HIV risk in the United States. Though a globally recognized service, the literature lacks U.S.-based health-care providers' (HCPs) perspectives of CHTC. To address this research gap, a qualitative descriptive design was used to ascertain HCPs' perceptions about CHTC. Semistructured in-depth interviews were conducted with 22 HCPs who were experienced with engaging patients or clients across the HIV care continuum. Overall, HCPs supported CHTC for different U.S. populations. Content analysis revealed that HCPs perceived CHTC to be an evolution from current HIV testing approaches and a mechanism to screen people who may not otherwise. CHTC was perceived to have biomedical and socio-behavioral merit that warranted consideration for implementation within health service settings and among populations with heightened vulnerability to HIV acquisition. This strategy was perceived to be a mechanism for introducing pre-exposure prophylaxis and conception health into one's practice. CHTC also signaled patients reorienting perceptions of personal health as being linked to the health of another individual. Providers recognized that couples have evolved to be increasingly nonheteronormative and thought that CHTC should be offered to all couples. However, participants also noted that HCPs in the United States need to be comfortable with promoting sexual health among various populations for implementation of CHTC to be successful

The Uses of Self and Space: Health Providers' Approaches to Engaging Patients into the HIV Care Continuum

In the context of HIV prevention, the provider–patient relationship has been found to profoundly impact HIV screening, patient initiation into HIV care, and adherence to medication following an HIV diagnosis. Given the importance of the provider–patient relationship, insight into provider approaches to cultivate such relationships is essential. Such insight could highlight considerations for provider engagement with patients that can address the current challenges in HIV prevention and treatment. This qualitative descriptive study sought to describe current health providers' approaches to engage patients into the HIV care continuum (HCC). Findings from the content and thematic analysis indicated that health providers ( N  = 22) used various approaches to engage patients/clients into HIV screening, and subsequent HIV care. Approaches were represented by an interpersonal process and a thematic analysis revealed the nuances in the approaches that manifested in the following themes: uses of self, normalizing disease, and engaging couples. This study demonstrated the importance for health providers to be aware of the specific context of patient's vulnerability to HIV infection and barriers to care. Self-awareness and the capability to self-reflect on one's personal practice also helped to ensure engagement of those vulnerable to infection or infected with HIV into the HCC