"It made me more confident that I have it under control": Patient and provider perspectives on moving to a two-drug ART regimen in the United States and Spain.

BACKGROUND: Two-drug regimens (2DR) to treat HIV infection have the potential to reduce long-term toxicity and increase therapeutic options for people living with HIV (PLHIV). Prior phase III trials, SWORD-1 and SWORD-2, as well as GEMINI-1 and GEMINI-2, have demonstrated that a dolutegravir-based 2DR is as effective as three- or four-drug regimens among virologically suppressed patients. Limited information exists, however, on patient and provider experiences with 2DR to inform roll-out and integration into routine clinical care. METHODS: We conducted 39 in-depth interviews with PLHIV currently on 2DR in the context of routine care and 8 of their clinical care providers in the United States (U.S.) and Spain. Participants included 33 male and 6 female PLHIV and 8 providers. Interview topics explored perceptions of and experiences with 2DR compared to prior anti-retroviral regimens (ARVs), side effects, patient satisfaction, and clinical performance. Interviews were audio-recorded, transcribed and analyzed using thematic content analysis. RESULTS: Participants viewed 2DR as a significant and positive advance, in terms of its ability to effectively treat HIV with reduced toxicity and essentially no reported side effects. Patients noted the central role providers played in the decision to switch to a 2DR regimen and, among U.S. participants, the importance of insurance coverage making this preferred option feasible. Patients and providers agreed that a 2DR regimen would be appropriate for any PLHIV regardless of whether they were treatment naïve or had significant experience with ARVs. CONCLUSIONS: Participants' experiences with a 2DR regimen were positive with no participants, reporting side effects and all reporting continued viral suppression. Providers valued the reduced toxicity offered by 2DR and served as the primary gateway to a transition to 2DR for patients in both settings. This study provides a foundation for further research on the transition to 2DR regimens in other populations and contexts including low- and middle-income settings.

Markov Mixed Effects Modeling Using Electronic Adherence Monitoring Records Identifies Influential Covariates to HIV Preexposure Prophylaxis.

Adherence is a major factor in the effectiveness of preexposure prophylaxis (PrEP) for HIV prevention. Modeling patterns of adherence helps to identify influential covariates of different types of adherence as well as to enable clinical trial simulation so that appropriate interventions can be developed. We developed a Markov mixed-effects model to understand the covariates influencing adherence patterns to daily oral PrEP. Electronic adherence records (date and time of medication bottle cap opening) from the Partners PrEP ancillary adherence study with a total of 1147 subjects were used. This study included once-daily dosing regimens of placebo, oral tenofovir disoproxil fumarate (TDF), and TDF in combination with emtricitabine (FTC), administered to HIV-uninfected members of serodiscordant couples. One-coin and first- to third-order Markov models were fit to the data using NONMEM® 7.2. Model selection criteria included objective function value (OFV), Akaike information criterion (AIC), visual predictive checks, and posterior predictive checks. Covariates were included based on forward addition (α = 0.05) and backward elimination (α = 0.001). Markov models better described the data than 1-coin models. A third-order Markov model gave the lowest OFV and AIC, but the simpler first-order model was used for covariate model building because no additional benefit on prediction of target measures was observed for higher-order models. Female sex and older age had a positive impact on adherence, whereas Sundays, sexual abstinence, and sex with a partner other than the study partner had a negative impact on adherence. Our findings suggest adherence interventions should consider the role of these factors.

Management of Hypertensive Patients With Multiple Drug Intolerances: A Single-Center Experience of a Novel Treatment Algorithm.

Multiple drug intolerance to antihypertensive medications (MDI-HTN) is an overlooked cause of nonadherence. In this study, 55 patients with MDI-HTN were managed with a novel treatment algorithm utilizing sequentially initiated monotherapies or combinations of maximally tolerated doses of fractional tablet doses, liquid formulations, transdermal preparations, and off-label tablet medications. A total of 10% of referred patients had MDI-HTN, resulting in insufficient pharmacotherapy and baseline office blood pressure (OBP) of 178±24/94±15 mm Hg. At baseline, patients were intolerant to 7.6±3.6 antihypertensives; they were receiving 1.4±1.1 medications. After 6 months on the novel MDI-HTN treatment algorithm, both OBP and home blood pressure (HBP) were significantly reduced, with patients receiving 2.0±1.2 medications. At 12 months, OBP was reduced from baseline by 17±5/9±3 mm Hg (P<.01, P<.05) and HBP was reduced by 11±5/12±3 mm Hg (P<.01 for both) while patients were receiving 1.9±1.1 medications. Application of a stratified medicine approach allowed patients to tolerate increased numbers of medications and achieved significant long-term lowering of blood pressure.

Patient-reported outcomes among patients with type 2 diabetes mellitus treated with dapagliflozin in a triple-therapy regimen for 52 weeks.

Patients with type 2 diabetes (T2DM) and inadequate glycaemic control on combination metformin (MET) and sulphonylurea (SU) were enrolled in a 24-week, double-blind, randomized, placebo-controlled study with a 28-week extension. The five-dimension EuroQol questionnaire (EQ-5D), SHIELD Weight Questionnaire-9 (WQ-9), Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were used to evaluate health status and health-related quality of life (HRQoL) at baseline and week 52. Patients with dapagliflozin 10 mg + MET + SU (n = 108) were compared with patients treated with placebo + MET + SU (n = 108), using a repeated-measures mixed model. EQ-5D visual analogue scale scores, IWQOL-Lite and DTSQ scores improved in the dapagliflozin and placebo groups from baseline to week 52; however, there was no significant difference between groups (p > 0.20). EQ-5D index scores remained the same from baseline to week 52 for dapagliflozin and placebo (p = 0.54). A numerically greater proportion of the dapagliflozin group reported improvement in all nine SHIELD WQ-9 items compared with placebo, and the difference was statistically significant for physical health (p = 0.017). Over 52 weeks of therapy, patients maintained their health status and HRQoL when dapagliflozin was added to the treatment.

Pill burden in hypertensive patients treated with single-pill combination therapy--an observational study.

INTRODUCTION: Hypertension is a condition which in many cases is treated with more than one drug. Additionally, patients with hypertension often suffer from other concomitant diseases, such as diabetes mellitus or dyslipidemia, which adds to the number of pills that patients need to take (pill burden). The aim of this study was to investigate the impact of this pill burden on patients with hypertension in clinical practice in Germany. METHODS: This prospective, open-label, observational study enrolled adult patients for whom their physician considered treatment with a single-pill combination of amlodipine, valsartan, and hydrochlorothiazide as indicated. At the start of the observation period, physicians and patients filled in a respective questionnaire. RESULTS: The questionnaires of 7,101 patients and 905 physicians were analyzed. The survey among the patients showed that the majority of patients felt burdened by the high number of pills to be taken. This was also seen as a potential reason for medication errors. Approximately half of the patients would be willing to make an out-of-pocket payment for reducing the number of pills to half. The results of the physician questionnaire indicate that the physicians were well aware of the set of problems that is generally associated with the high pill burden and that there is a clear willingness to use combination products in order to reduce the pill burden. CONCLUSION: A high number of pills is considered a burden by the patients. This burden increases with the number of pills taken per day.

A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer's disease.

OBJECTIVE: This study examined the effects of modafinil on apathetic symptomatology, performance of activities of daily living (ADLs), and caregiver burden in individuals with Alzheimer's disease (AD). METHOD: 23 participants with a diagnosis of mild-to-moderate probable AD according to National Institute of Neurologic and Communicative Disorder and Stroke-Alzheimer's Disease and Related Disorders criteria were randomized into the experimental (modafinil 200 mg daily) or control (placebo) groups. All participants were also receiving stable doses of a cholinesterase inhibitor medication. Participants completed assessments at baseline and after 8 weeks of treatment. Outcome measures included family report measures of apathy, ADL performance, and caregiver burden, as well as direct assessment of ADL performance. The study was conducted at a private psychiatric hospital in Rhode Island from September 2005 until September 2007. RESULTS: Both the experimental and control groups showed reductions in apathy on the Frontal Systems Behavior Scale between baseline and final assessments (F1,20 = 18.017, P < .001, η2 = 0.474), and there was no significant additional reduction in apathy with modafinil (F1,20 = 0.008, P = .932, η2 = 0.000). Groups did not show significant changes in caregiver report of ADL performance over time (F1,19 = 0.268, P = .611). The correlation between change in apathy and change in caregiver burden was not significant (r = 0.355, P = .053), but there was a trend toward improved levels of apathy being related to decreased levels of caregiver burden. CONCLUSIONS: The addition of modafinil to the standard of care treatment (cholinesterase inhibitor medication) did not result in significant additional reductions in apathy or improvements in ADL functioning. The reduction in reported apathy observed in both groups between baseline and final assessments was likely due to placebo effect. However, reductions in perceived apathetic symptomatology were correlated with reductions in reported caregiver distress and burden. Larger studies with more statistical power are needed to confirm the absence of significant effects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01172145.

Assessment of treatment algorithms including amantadine, metformin, and zonisamide for the prevention of weight gain with olanzapine: a randomized controlled open-label study.

OBJECTIVE: This 22-week, open-label study, conducted between November 2006 and September 2008 in a community setting, was designed to determine if weight gain during olanzapine treatment can be prevented or mitigated with adjunctive treatment algorithms that include amantadine, metformin, and zonisamide. METHOD: Outpatients with schizophrenia or schizoaffective disorder (DSM-IV-TR criteria) were randomly assigned to olanzapine alone (n = 50), olanzapine plus algorithm A (olanzapine + A [amantadine 200 mg/d with possible switches to metformin 1,000-1,500 mg/d and then to zonisamide 100-400 mg/d; n = 76]), or olanzapine plus algorithm B (olanzapine + B [metformin 1,000-1,500 mg/d with possible switches to amantadine 200 mg/d and then to zonisamide 100-400 mg/d; n = 73]). Brief weight management education was provided at baseline. The primary outcome measure was comparison of mean weight gain between olanzapine and pooled olanzapine + A and olanzapine + B results. RESULTS: Least squares mean ± SE weight gain was 2.76 ± 0.75 kg for olanzapine, 2.40 ± 0.65 kg for olanzapine + A, and 0.65 ± 0.63 kg for olanzapine + B. Mean weight gain during olanzapine treatment did not differ significantly from pooled results for olanzapine + A and olanzapine + B (P = .065). Participants treated with olanzapine + B experienced significantly less mean weight gain than olanzapine-treated participants (P = .036). CONCLUSIONS: Pooled treatment algorithm results were not significantly different from olanzapine monotherapy in mitigating weight gain. However, participants who received treatment with metformin with possible progression to amantadine and then zonisamide had significantly less mean weight gain than participants treated with olanzapine alone. Progression of some participants through the algorithm indicated that a single therapy solution may not be adequate for every patient. Patients treated with olanzapine should receive regular weight monitoring. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00401973.