Mitochondrial creatine sensitivity is lost in the D2.mdx model of Duchenne muscular dystrophy and rescued by the mitochondrial-enhancing compound Olesoxime.

Duchenne muscular dystrophy (DMD) is associated with distinct mitochondrial stress responses. Here, we aimed to determine whether the prospective mitochondrial-enhancing compound Olesoxime, prevents early-stage mitochondrial stress in limb and respiratory muscle from D2.mdx mice using a proof-of-concept short-term regimen spanning 10-28 days of age. As mitochondrial-cytoplasmic energy transfer occurs via ATP- or phosphocreatine-dependent phosphate shuttling, we assessed bioenergetics with or without creatine in vitro. We observed that disruptions in Complex I-supported respiration and mH2O2 emission in D2.mdx quadriceps and diaphragm were amplified by creatine demonstrating mitochondrial creatine insensitivity manifests ubiquitously and early in this model. Olesoxime selectively rescued or maintained creatine sensitivity in both muscles, independent of the abundance of respiration-related mitochondrial proteins or mitochondrial creatine kinase cysteine oxidation in quadriceps. Mitochondrial calcium retention capacity and glutathione were altered in a muscle-specific manner in D2.mdx but were generally unchanged by Olesoxime. Treatment reduced serum creatine kinase (muscle damage) and preserved cage hang-time, microCT-based volumes of lean compartments including whole body, hindlimb and bone, recovery of diaphragm force after fatigue, and cross-sectional area of diaphragm type IIX fiber, but reduced type I fibers in quadriceps. Grip strength, voluntary wheel-running and fibrosis were unaltered by Olesoxime. In summary, locomotor and respiratory muscle mitochondrial creatine sensitivities are lost during early stages in D2.mdx mice but are preserved by short-term treatment with Olesoxime in association with specific indices of muscle quality suggesting early myopathy in this model is at least partially attributed to mitochondrial stress.

The Magnetic Levator Prosthesis for Temporary Management of Severe Blepharoptosis: Initial Safety and Efficacy.

PURPOSE: We further optimized and evaluated the safety of the magnetic levator prosthesis (MLP) for temporary management of severe blepharoptosis, and compared efficacy and comfort against the ptosis crutch. METHODS: The interpalpebral fissure (IPF) of participants (n = 12) with ptosis was measured during attempted eyelid opening, volitional closing, and spontaneous closing with no device, ptosis crutch, or the MLP. A 10-point scale documented comfort. Additionally, a 20 minute and then 1 week trial of the MLP was offered. Safety measures were skin erythema rating, change in visual acuity, and change in corneal staining. RESULTS: The MLP and crutch opened the eye (IPF 11.2 and 9.3 mm), but the MLP allowed better volitional closure (IPF 1.0 vs. 4.9 mm, P = 0.009), but was no better in allowing spontaneous blink (IPF 7.5 vs. 7.7 mm, P = 0.722). Both devices were equally comfortable (both median 8/10 comfort, P = 0.46). With extended use, opening with the MLP showed IPF 9.24 mm at 20 minutes and 9.46 mm at 1 week, and volitional closure was IPF 0.95 and 0.52 mm, respectively. Closure on spontaneous blink improved with extended wear to IPF 5.14 and 5.18 mm, respectively (P = 0.002). Two participants exhibited moderate skin erythema and one had increased corneal staining without change in acuity. CONCLUSIONS: The MLP is safe and feasible for temporary correction of severe ptosis. TRANSLATIONAL RELEVANCE: First group data in patients showing successful reanimation of the eyelid with magnetic force.

Food insecurity and antiretroviral adherence among HIV positive adults who drink alcohol.

Food insecurity is associated with HIV treatment non-adherence and poor health outcomes for people living with HIV/AIDS. Given the poor nutritional status common to people who drink alcohol, food insecurity may be particularly problematic for HIV positive individuals who drink alcohol. To examine food insecurity among HIV positive men and women who drink alcohol and its association with antiretroviral therapy (ART) adherence, health outcomes and health service utilization. Adults living with HIV (N = 183) in Atlanta, Georgia who reported alcohol use in the previous week and were receiving ART participated in a 12-month cohort. Participants were recruited from infectious disease clinics and social services to complete computerized interviews, monthly-unannounced pill counts to monitor ART adherence, and daily cell-phone delivered interactive-text assessments for alcohol use. Forty-three percent of participants experienced food insecurity during at least one month of the study period. Food insecurity was independently associated with suboptimal ART adherence and less suppressed HIV viral load over. Individuals who experienced food insecurity also had histories of more medical and psychiatric hospitalizations, and greater mental health problems. Food insecurity is prevalent among alcohol using people receiving ART and food insecurity is associated with treatment non-adherence, poor health outcomes, and increased medical and psychiatric hospitalizations.

Viral suppression and antiretroviral medication adherence among alcohol using HIV-positive adults.

BACKGROUND: Substance use is a known predictor of poor adherence to antiretroviral therapies (ART) in people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Less studied is the association between substance use and treatment outcomes, namely, suppression of HIV replication. METHODS: Adults living with HIV (N = 183) who reported alcohol use in the previous week and receiving ART were observed over a 12-month period. Participants completed computer interviews, monthly unannounced pill counts to monitor ART adherence, and daily cell-phone delivered interactive-text assessments for alcohol use. HIV viral load was collected at baseline and 12-month follow-up from medical records. Analyses compared participants who had undetectable HIV viral loads at baseline and follow-up (sustained viral suppression) to those with unsustained viral suppression. Analyses also compared participants who were adherent to their medications (>85 % pills taken) over the year of observation to those who were nonadherent. RESULTS: Fifty-two percent of participants had unsustained viral suppression; 47 % were ART nonadherent. Overall results failed to demonstrate alcohol use as a correlate of sustained viral suppression or treatment adherence. However, alcohol use was associated with nonadherence among participants who did not have sustained viral suppression; nonadherence in unsustained viral suppression patients was related to drinking on fewer days of assessment, missing medications when drinking, and drinking socially. CONCLUSIONS: Poor HIV treatment outcomes and nonadherence were prevalent among adults treated for HIV infection who drink alcohol. Drinking in relation to missed medications and drinking in social settings are targets for interventions among alcohol drinkers at greatest risk for poor treatment outcomes.

Randomized clinical trial of HIV treatment adherence counseling interventions for people living with HIV and limited health literacy.

BACKGROUND: Limited health literacy is a known barrier to medication adherence among people living with HIV. Adherence improvement interventions are urgently needed for this vulnerable population. PURPOSE: This study tested the efficacy of a pictograph-guided adherence skills-building counseling intervention for limited literacy adults living with HIV. METHODS: Men and women living with HIV and receiving antiretroviral therapy (N = 446) who scored <90% correct on a test of functional health literacy were partitioned into marginal and lower literacy groups and randomly allocated to 1 of 3 adherence-counseling conditions: (1) pictograph-guided adherence counseling, (2) standard adherence counseling, or (3) general health improvement counseling. Participants were followed for 9 months postintervention with unannounced pill count adherence and blood plasma viral load as primary end points. RESULTS: Preliminary analyses demonstrated the integrity of the trial and >90% of participants were retained. Generalized estimating equations showed significant interactions between counseling conditions and levels of participant health literacy across outcomes. Participants with marginal health literacy in the pictograph-guided and standard-counseling conditions demonstrated greater adherence and undetectable HIV viral loads compared with general health counseling. In contrast and contrary to hypotheses, participants with lower health literacy skills in the general health improvement counseling demonstrated greater adherence compared with the 2 adherence counseling conditions. CONCLUSIONS: Patients with marginal literacy skills benefit from adherence counseling regardless of pictographic tailoring, and patients with lower literacy skills may require more intensive or provider-directed interventions.

Intentional non-adherence to medications among HIV positive alcohol drinkers: prospective study of interactive toxicity beliefs.

BACKGROUND: Antiretroviral therapy (ART) adherence is key to successful treatment of HIV infection and alcohol is a known barrier to adherence. Beyond intoxication, ART adherence is impacted by beliefs that mixing alcohol and medications is toxic. PURPOSE: To examine prospective relationships of factors contributing to intentional medication non-adherence when drinking. METHODS: People who both receive ART and drink alcohol (N = 178) were enrolled in a 12-month prospective cohort study that monitored beliefs about the hazards of mixing ART with alcohol (interactive toxicity beliefs), alcohol consumption using electronic daily diaries, ART adherence assessed by both unannounced pill counts and self-report, and chart-abstracted HIV viral load. RESULTS: Participants who reported skipping or stopping their ART when drinking (N = 90, 51 %) demonstrated significantly poorer ART adherence, were less likely to be viral suppressed, and more likely to have CD4 counts under 200/cc(3). Day-level analyses showed that participants who endorsed interactive toxicity beliefs were significantly more likely to miss medications on drinking days. CONCLUSIONS: Confirming earlier cross-sectional studies, the current findings from a prospective cohort show that a substantial number of people intentionally skip or stop their medications when drinking. Interventions are needed to correct alcohol-related interactive toxicity misinformation and promote adherence among alcohol drinkers.

Alcohol and adherence to antiretroviral medications: interactive toxicity beliefs among people living with HIV.

When taken without interruption, antiretroviral therapies (ART) effectively treat HIV infection. Alcohol is a well-known direct and indirect influence on ART adherence. Believing that drinking is harmful while taking ART (interactive toxicity beliefs) is also associated with poor adherence. The current study included 333 people living with HIV who were taking ART and actively using alcohol. Participants were recruited from health care providers and social services in a major southern U.S. city. Results showed that 52% of persons found non-adherent to ART stated that they stopped taking their medications when they were drinking. Multivariate analyses showed that interrupting treatment when drinking was related to current non-adherence, over and above several common correlates of non-adherence including frequency of alcohol use itself. These results confirm and extend past research, indicating an urgent need for medication adherence interventions designed for people living with HIV who drink.

Falling through the cracks: unmet health service needs among people living with HIV in Atlanta, Georgia.

Despite growing numbers of people living with HIV (PLWH), the landscape of related services is shrinking. This study investigated health and social service needs of men (N = 489) and women (N = 165) living with HIV in Atlanta, GA. Participants completed confidential measures asking about the health and social services they needed and accessed. Results showed an array of health and social service needs among PLWH; failure to access services was prevalent. Hunger was among the most common basic needs, reported by greater than 60% of men and women. For men, unmet service needs were associated with fewer years since testing positive for HIV, higher CD4+ T cell values, experiencing more stressors and depression, and greater quantity of alcohol use. For women, failure to access services was associated with experiencing depression and not receiving HIV medications. Providing basic services to PLWH remains a public health priority and a moral imperative.

Brief behavioral self-regulation counseling for HIV treatment adherence delivered by cell phone: an initial test of concept trial.

Affordable and effective antiretroviral therapy (ART) adherence interventions are needed for many patients to promote positive treatment outcomes and prevent viral resistance. We conducted a two-arm randomized trial (n = 40 men and women receiving and less than 95% adherent to ART) to test a single office session followed by four biweekly cell phone counseling sessions that were grounded in behavioral self-management model of medication adherence using data from phone-based unannounced pill counts to provide feedback-guided adherence strategies. The control condition received usual care and matched office and cell phone/pill count contacts. Participants were baseline assessed and followed with biweekly unannounced pill counts and 4-month from baseline computerized interviews (39/40 retained). Results showed that the self-regulation counseling delivered by cell phone demonstrated significant improvements in adherence compared to the control condition; adherence improved from 87% of pills taken at baseline to 94% adherence 4 months after baseline, p < 0.01. The observed effect sizes ranged from moderate (d = 0.45) to large (d = 0.80). Gains in adherence were paralleled with increased self-efficacy (p < 0.05) and use of behavioral strategies for ART adherence (p < 0.05). We conclude that the outcomes from this test of concept trial warrant further research on cell phone-delivered self-regulation counseling in a larger and more rigorous trial.

Integrated behavioral intervention to improve HIV/AIDS treatment adherence and reduce HIV transmission.

OBJECTIVES: We conducted a randomized clinical trial to test an integrated behavioral intervention designed to enhance using HIV treatment as prevention by improving medication adherence, reducing risks for other sexually transmitted infections, and minimizing risk compensation beliefs. METHODS: Individuals living with HIV/AIDS (n = 436) participated in a randomized clinical trial testing an intensive behavioral intervention aimed at reducing HIV transmission risks compared with an attention control condition. We used unannounced pill counts to monitor antiretroviral therapy adherence and computerized interviews to measure risk behaviors. RESULTS: The integrated transmission risk reduction intervention demonstrated increased antiretroviral therapy adherence and less unprotected intercourse with nonseroconcordant partners at 3- and 6-month follow-ups as well as fewer new sexually transmitted infections diagnosed over the 9-month follow-up period (adjusted odds ratio = 3.0; P < .05; 95% confidence interval = 1.01, 9.04). The integrated intervention also reduced behavioral risk compensation beliefs. CONCLUSIONS: A theory-based integrated behavioral intervention can improve HIV treatment adherence and reduce HIV transmission risks. HIV treatment as prevention should be bundled with behavioral interventions to maximize effectiveness.

HIV super-infection beliefs and sexual practices of people living with HIV/AIDS.

BACKGROUND: People living with HIV can be reinfected with a new viral strain resulting in potential treatment-resistant recombinant virus known as HIV super-infection. Individual's beliefs about the risks for HIV super-infection may have significant effects on the sexual behaviours of people living with HIV/AIDS. HIV super-infection beliefs and sexual behaviours among people living with HIV/AIDS were examined in the present study. METHODS: Three hundred and twenty men, 137 women, and 33 transgender persons completed confidential surveys in a community research setting. RESULTS: A majority of participants were aware of HIV super-infection and most believed it was harmful to their health. Hierarchical multiple regressions predicting protected anal/vaginal intercourse with same HIV status (seroconcordant) partners showed that older age and less alcohol use were associated with greater protected sex. In addition, HIV super-infection beliefs predicted protected sexual behaviour over and above participant age and alcohol use. CONCLUSIONS: Beliefs about HIV super-infection exert significant influence on sexual behaviours of people living with HIV/AIDS and should be targeted in HIV prevention messages for HIV infected persons.

Adherence to antiretroviral therapy and HIV transmission risks: implications for test-and-treat approaches to HIV prevention.

HIV transmission may be prevented by effectively suppressing viral replication with antiretroviral therapy (ART). However, adherence is essential to the success of ART, including for reducing HIV transmission risk behaviors. This study examined the association of nonadherence versus adherence with HIV transmission risks. Men (n = 226) living with HIV/AIDS and receiving ART completed confidential computerized interviews and telephone-based unannounced pill counts for ART adherence monitoring. Data were collected between January 2008 and June 2009. Results showed that nonadherence to ART was associated with greater number of sex partners and engaging in unprotected and protected anal intercourse. These associations were not moderated by substance use. The belief that having an undetectable viral load leads to lower infectiousness was associated with greater number of partners, including nonpositive partners, and less condom use. Men who had an undetectable viral load and believed that having an undetectable viral load reduces their infectiousness, were significantly more likely to have contracted a recent STI. Programs aimed at testing and treating people living with HIV/AIDS for prevention require attention to adherence and sexual behaviors.

Health and treatment implications of food insufficiency among people living with HIV/AIDS, Atlanta, Georgia.

HIV/AIDS is concentrated among the inner-city poor and poverty may directly interfere with HIV treatment. This study examined food insufficiency in relation to HIV-related health and treatment. A sample of 344 men and women living with HIV/AIDS in Atlanta, Georgia completed measures of food security, health, and HIV disease progression and treatment. HIV treatment adherence was monitored using unannounced pill counts. Results showed that half of people living with HIV/AIDS in this study lacked sufficient food, and food insufficiency was associated with multiple indicators of poor health, including higher HIV viral loads, lower CD4 cell counts, and poorer treatment adherence. Adjusted analyses showed that food insufficiency predicted HIV treatment non-adherence over and above years of education, employment status, income, housing, depression, social support, and non-alcohol substance use. Hunger and food insecurity are prevalent among people living with HIV/AIDS, and food insufficiency is closely related to multiple HIV-related health indicators, particularly medication adherence. Interventions that provide consistent and sustained meals to people living with HIV/AIDS are urgently needed.

Monthly unannounced pill counts for monitoring HIV treatment adherence: tests for self-monitoring and reactivity effects.

BACKGROUND: Unannounced home-based pill counts conducted in person or on the telephone are reliable and valid for monitoring medication adherence. However, expecting to have one's pills counted, organizing medications for pill counts, and increased attention from the person conducting the pill counts may have reactive effects and inadvertently improve adherence. The current study determined whether monthly unannounced pill counts conducted by telephone influence adherence over time. METHODS: Two prospective cohorts, one drawn from a social support condition in a behavioral intervention trial (n=186) and the other an observational study (n=187), were followed for 12 months and 8 months, respectively. Medication adherence was monitored using monthly unannounced pill counts conducted by telephone. In addition, blood plasma viral load was collected at the final pill count for the observational cohort. RESULTS: Analyses did not indicate increases in medication adherence over time for antiretroviral or psychiatric medications among men, women, people with detectable and undetectable viral loads, and various medication regimens. CONCLUSIONS: Unannounced pill counts conducted by telephone do not demonstrate reactivity effects and remain a viable, unobtrusive, objective method of monitoring medication adherence.

A simple single-item rating scale to measure medication adherence: further evidence for convergent validity.

BACKGROUND: Self-report measures of medication adherence are inexpensive and minimally intrusive. However, the validity of self-reported adherence is compromised by recall errors for missed doses and socially desirable responding. METHOD: Examined the convergent validity of 2 self-report adherence measures administered by computerized interview: (a) recall of missed doses and (b) a single-item visual analogue rating scale (VAS). Adherence was also monitored using unannounced phone-based pill counts that served as an objective benchmark. RESULTS: The VAS obtained adherence estimates that paralleled unannounced pill counts (UPCs). In contrast, self-reported recall (SR-recall) of missed medications consistently overestimated adherence. Correlations with participant characteristics also suggested that the computer-administered VAS was less influenced by response biases than SR-recall of missed medication doses. CONCLUSIONS: A single-item VAS offers an inexpensive and valid method of assessing medication adherence that may be useful in clinical as well as research settings.

Prevalence and clinical implications of interactive toxicity beliefs regarding mixing alcohol and antiretroviral therapies among people living with HIV/AIDS.

Alcohol use is a barrier to medication adherence. Beyond the cognitive effects of intoxication, people living with HIV/AIDS who believe that alcohol should not be mixed with their medications may temporarily stop taking medications when drinking. To examine the effects of alcohol-treatment beliefs on HIV treatment adherence. People living with HIV/AIDS who were receiving treatment (n = 145) were recruited from community and clinical services during the period between January 2006 and May 2008 to complete measures of substance use and alcohol-antiretroviral (ARV) interactive toxicity beliefs (e.g., alcohol breaks down HIV medications so they will not work). Medication adherence was monitored using unannounced telephone-based pill counts. Forty percent of participants were currently using alcohol and nearly one in four drinkers reported stopping their medications when drinking. Beliefs that mixing alcohol and medications is toxic were common among drinkers and nondrinkers, with most beliefs endorsed more frequently by non-drinkers. Hierarchical regression analysis showed that stopping ARVs when drinking was associated with treatment nonadherence over and above quantity/frequency of alcohol use and problem drinking. Beliefs that alcohol and ARVs should not be mixed and that treatments should be interrupted when drinking are common among people living with HIV/AIDS. Clinicians should educate patients about the necessity of continuing to take ARV medications without interruption even if they are drinking alcohol.

Association between health literacy and HIV treatment adherence: further evidence from objectively measured medication adherence.

BACKGROUND: People with lower-health literacy are vulnerable to health problems. Studies that have examined the association between literacy and medication adherence have relied on self-reported adherence, which is subject to memory errors, perhaps even more so in people with poor literacy. PURPOSE: To examine the association between health literacy and objectively assessed HIV treatment adherence. METHODS: Men and women (N = 145) receiving antiretroviral therapy completed a test of health literacy and measures of common adherence markers. Medication adherence was monitored by unannounced pill counts. RESULTS: Median adherence was 71%; participants with lower-health literacy also demonstrated poorer adherence compared to participants with higher literacy. Hierarchical regression showed literacy predicted adherence over and above all other factors. Sensitivity tests showed the same results for 80% and 90% adherence. CONCLUSIONS: The association between literacy and adherence appears robust and was confirmed using an objective measure of medication adherence.

Monitoring medication adherence by unannounced pill counts conducted by telephone: reliability and criterion-related validity.

BACKGROUND: Although demonstrated valid for monitoring medication adherence, unannounced pill counts conducted in patients' homes are costly and logistically challenging. Telephone-based unannounced pill counts offer a promising adaptation that resolves most of the limitations of home-based pill counting. PURPOSE: We tested the reliability and criterion-related validity of a telephone-based unannounced pill count assessment of antiretroviral adherence. METHOD: HIV-positive men and women (N = 89) in Atlanta, Georgia, completed a telephone-based unannounced pill count and provided contemporaneous blood specimens to obtain viral loads; 68 participants also received an immediate second pill count conducted during an unannounced home visit. RESULTS: A high degree of concordance was observed between the number of pills counted on the telephone and in the home (intraclass correlation [ICC] = .981, p < .001) and percent of pills taken (ICC = .987, p < .001). Adherence obtained by the telephone count and home count reached 92% agreement (Kappa coefficient = .94). Adherence determined by telephone-based pill counts also corresponded with patient viral load, providing evidence for criterion-related validity. CONCLUSION: Unannounced telephone-based pill counts offer a feasible objective method for monitoring medication adherence.

Serosorting sexual partners and risk for HIV among men who have sex with men.

OBJECTIVE: The purpose of the current study was to assess whether men who have sex with men (MSM) who limit their unprotected anal sexual partners to those who are of the same HIV status (serosort) differ in their risk for HIV transmission than MSM who do not serosort. METHODS: Cross-sectional surveys administered at a large Gay Pride festival in June 2006 (80% response rate) were collected from MSM. Univariate and multivariate logistic regressions were used to identify predictors of serosorting. Analyses were conducted in 2006. RESULTS: Participants were self-identified as HIV-negative MSM (N=628); about one third of them engaged in serosorting (n=229). Men who serosort were more likely to believe that it offered protection against HIV transmission, perceived themselves as being at no relatively higher risk for HIV transmission, and had more unprotected anal intercourse partners. Over half the sample reported their frequency of HIV testing as yearly or less frequently; this finding did not differ between serosorters and nonserosorters. CONCLUSIONS: Men who identify as HIV-negative and serosort are no more likely to know their HIV status than men who do not serosort and are at higher risk for exposure to HIV. Interventions targeting MSM must address the limitations of serosorting.