"I feel empowered": women's perspectives on and experiences with long-acting injectable antiretroviral therapy in the USA and Spain.

Long-acting injectable antiretroviral therapy has been shown to be non-inferior to daily oral antiretroviral therapy in clinical trials and may soon become part of clinical care. While most trial participants to date have been men, approximately one quarter of ongoing Phase 3 trial participants are women offering an important opportunity to understand how long-acting antiretroviral therapy is perceived and experienced by women. We conducted in-depth interviews with 80 people living with HIV participating in Phase 2 and 3 clinical trials of long-acting antiretroviral therapy in the USA and Spain. Fifteen percent (12/80) of trial participants interviewed were women. Interviews were audio-recorded, transcribed and coded using content analysis, focused on gender-specific themes. Women shared many of the positive perceptions expressed by men but also had unique perspectives, including finding that long-acting antiretroviral therapy addressed the challenge of remembering pills amidst busy day-to-day realities including multiple roles and responsibilities, is less time consuming and creates less stress compared to oral antiretroviral therapy, and is emotionally freeing and empowering. The gendered nature of women's lives shaped why and how they were satisfied with long-acting antiretroviral therapy. Findings can inform interventions and support systems to facilitate uptake of and adherence to long-acting antiretroviral therapy in women.

The prevalence and burden of systemic lupus erythematosus in a medicare population: retrospective analysis of medicare claims.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder which can affect multiple organs of the body, requiring ongoing disease management and healthcare resource utilization. The economic impact of SLE has not been evaluated in a Medicare population to date. This study was conducted to assess the prevalence of SLE and its burden in terms of healthcare resource utilization and costs in a US Medicare population. METHODS: This was a retrospective observational study using Medicare medical claims data (5% random sample) for the period spanning 2003 to 2007. SLE patients were identified by having ≥2 medical claims with a primary or secondary diagnosis of ICD-9 code 710.0X. The earliest quarter of SLE diagnosis was defined as the index quarter. Prevalence of SLE, the proportion of SLE cases on disability benefits, and the contribution of SLE to new disability cases were evaluated. Healthcare resource utilization and direct medical costs (2008 US dollars) over 12 months were compared between a cohort of patients with SLE and a cohort without SLE matched on key demographics. Differences in outcomes between cohorts were assessed using McNemar's test for dichotomous variables and paired t-tests for continuous variables. RESULTS: A total of 13,348 patients with SLE were identified. The prevalence of SLE was approximately 3 per 1000 Medicare beneficiaries. After matching, the sample consisted of 6,707 SLE and 13,414 non-SLE patients. On average, the SLE cohort compared with the non-SLE cohort had 2.4 times more physician visits, 2.7 times more hospitalizations, 2.2 times more outpatient visits, and 2.1 times more emergency room visits. A medical cost surplus of approximately $10,229 per patient per year in the SLE cohort relative to the non-SLE cohort was driven largely by inpatient hospitalization costs (p < 0.001). CONCLUSIONS: SLE prevalence was 3 per 1,000 Medicare patients. Patients with SLE consumed significantly more health care resources with significantly greater costs compared with those without SLE. Added costs were largely attributable to inpatient hospitalizations. The Medicare population is an important target for efforts to improve SLE disease management and reduce costs.

Reliability, validity, and responsiveness of the Rhinitis Control Assessment Test in patients with rhinitis.

BACKGROUND: The Rhinitis Control Assessment Test (RCAT) is a brief, patient-completed tool to evaluate rhinitis symptom control. OBJECTIVE: We sought to test the reliability, validity, and responsiveness of RCAT and to estimate a cut-point score and minimal important difference (MID). METHODS: A total of 402 patients 12 years of age and older with allergic or nonallergic rhinitis were enrolled in a noninterventional study. Patients completed the RCAT (6 items; score range, 6-30) and had Total Nasal Symptom Scores (TNSSs) measured at baseline and 2 weeks later. Physicians completed a global assessment of rhinitis symptom control (Physician's Global Assessment) and disease severity. Internal consistency, test-retest reliability, convergent validity, known-groups validity, and responsiveness were evaluated. The MID was determined by using distribution- and anchor-based methods. Content validity of the RCAT was assessed in individual interviews with a separate group of 58 adult patients. RESULTS: Internal consistency and test-retest reliability of RCAT scores were 0.77 and 0.78, respectively. Convergent validity correlation between RCAT and TNSS scores was 0.57, and that between RCAT and Physician's Global Assessment scores was 0.34. Mean RCAT scores differed significantly (P < .001) across patient groups, differing in TNSS (F = 72.7), Physician's Global Assessment score (F = 28.6), and disease severity (F = 34.1) in the hypothesized direction. Results suggested a cut-point score of 21 or less can be used to identify patients who are experiencing rhinitis symptom control problems. The preliminary estimate of the MID was 3 points. Patients found RCAT items comprehensive, easy to understand, and relevant. CONCLUSION: The RCAT demonstrated adequate reliability, validity, and responsiveness and was deemed acceptable and appropriate by patients. This tool can facilitate the detection of rhinitis symptom control problems, and its brevity supports its usefulness in clinical care.

Cabotegravir + Rilpivirine Long-Acting: Overview of Injection Guidance, Injection Site Reactions, and Best Practices for Intramuscular Injection Administration.

Background: Cabotegravir (CAB) + rilpivirine (RPV) dosed monthly or every 2 months is a complete long-acting (LA) regimen for the maintenance of human immunodeficiency virus type 1 virologic suppression. Across the phase 3/3b trials, the most frequently reported adverse events were injection site reactions (ISRs). Methods: We present pooled ISR characteristics and outcomes for participants receiving CAB + RPV LA through week 96 of the FLAIR and ATLAS-2M studies, and survey results from healthcare providers (HCPs) giving injections (eg, injectors) in the ATLAS, FLAIR, and ATLAS-2M studies to determine optimal injection techniques. Surveys were anonymous, self-administered online questionnaires that queried provider demographics, injection experience, and techniques to minimize pre-/postinjection discomfort. Data were summarized using descriptive statistics. Results: Overall, 8453 ISRs were reported by 801 participants receiving ≥1 injection of CAB LA/RPV LA. Most ISRs were mild to moderate in severity (grade 1-2, 99%), with a median duration of 3 days (interquartile range, 2-4 days), and rarely led to withdrawal (2%). Surveys were completed by 181 HCPs across 113 sites. Pushing the intramuscular injection at slow speed (66%), bringing the medication to room temperature (58%), and relaxing the gluteus muscle before injecting (53%) were ranked as effective preinjection/injection procedure practices for minimizing pain. Most injectors (60%) indicated that a prone position provided optimal patient comfort, and 41% had no preference on injection medication order. Conclusions: Taken together, the data demonstrate favorable tolerability with CAB + RPV LA injections over the long term and simple techniques routinely used by injectors to help optimize the administration of CAB + RPV LA injections.

Fluticasone furoate nasal spray reduces symptoms of uncomplicated acute rhinosinusitis: a randomised placebo-controlled study.

BACKGROUND: Uncomplicated acute rhinosinusitis (ARS) is usually a self-limiting inflammatory condition often treated with antibiotics. AIMS: To assess the safety and efficacy of fluticasone furoate nasal spray (FFNS) compared with placebo for symptomatic relief of uncomplicated ARS. METHODS: A randomised, double-blind, placebo-controlled, parallel-group, multicentre, 2-week treatment study of FFNS 110 µg once and twice daily was undertaken in adults/adolescents. RESULTS: A statistically significant reduction was seen in the daily major symptoms score, a composite score of three individual symptoms (nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip on a 0-3 scale) by both FFNS doses compared with placebo (least square mean differences vs. placebo of -0.386 (p=0.008) and -0.357 (p=0.014) for once daily and twice daily FFNS, respectively). The differences in median times to symptom improvement were not statistically significant between each dose of FFNS (7 days) and placebo (8 days). There were no treatment differences in antibiotic use for possible fulminant bacterial rhinosinusitis (3% in each group). The safety profile of FFNS was similar to placebo. CONCLUSIONS: FFNS reduces symptoms of uncomplicated ARS compared with placebo and is well tolerated, providing support for withholding antibiotics in selected patients.

Patient and Physician Preferences for Regimen Attributes for the Treatment of HIV in the United States and Canada.

A long-acting injectable (LAI) antiretroviral therapy (ART) regimen is now available as a treatment option for virologically suppressed adults with HIV-1. This study assessed preference for a LAI regimen using an online survey of virally suppressed people living with HIV (PLWH) and physicians treating HIV in the US and Canada. Preference was elicited in a discrete choice experiment (DCE) with three choice options (switch to a LAI regimen, switch to another daily oral ART regimen, or stay on their current daily oral ART regimen) and four treatment attributes. A total of 553 PLWH and 450 physicians completed the survey. From the DCE results, 59% of PLWH were predicted to prefer a LAI over an alternative oral ART or staying on their current oral treatment, and 55-66% of physicians were predicted to recommend LAI for PLWH, depending on the treatment challenge scenario presented. PLWH indicated LAI would remove daily reminders of HIV (75%) and reduce feelings of being stigmatized (68%). A majority of PLWH and physicians preferred a LAI over oral ART to overcome treatment challenges such as daily pill burden and adherence. These benefits of LAI ART along with preferences of PLWH and physicians can help to inform ART choice.

Perspectives of healthcare providers on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings from a Hybrid III Implementation-effectiveness study (CUSTOMIZE).

INTRODUCTION: CUSTOMIZE evaluated the implementation of long-acting (LA) cabotegravir + rilpivirine, a novel healthcare provider-administered injectable antiretroviral therapy regimen, in diverse US healthcare settings. Findings from staff-study participants (SSPs) through 12 months of implementation are reported. METHODS: CUSTOMIZE was a phase IIIb, 12-month, single-arm, hybrid III implementation-effectiveness study conducted from July 2019 to October 2020 at eight US clinics of five clinic types: private practice (n = 2), federally qualified health centre (n = 2), university (n = 2), AIDS Healthcare Foundation (n = 2) and health maintenance organization (n = 1). Eligible patient participants received monthly cabotegravir + rilpivirine LA injections after a 1-month oral lead-in. At baseline, month 4 and month 12, SSPs (n = 3 each per clinic), including physicians, nurses or injectors, and administrators, completed quantitative surveys and semi-structured interviews to assess implementation outcomes (acceptability, appropriateness and feasibility of intervention measures), programme sustainability and SSP perceptions of, attitudes towards, and expectations for cabotegravir + rilpivirine LA. Month 12 data collection occurred during the COVID-19 pandemic. RESULTS: In surveys, SSPs reported high mean total scores for acceptability, appropriateness and feasibility of cabotegravir + rilpivirine LA implementation at baseline (4.43, 4.52 and 4.38 of 5, respectively) and month 12 (4.45, 4.61 and 4.46 of 5, respectively), regardless of clinic type. At month 12, SSPs were positive about the implementation sustainability (mean Program Sustainability Assessment Tool score, 5.83 out of 7). At baseline, SSPs' top concern was patients' ability to maintain monthly appointments (81%); at month 12, 39% had this concern. The proportion of SSPs reporting patient injection pain or soreness as a barrier was consistent at month 12 versus baseline (48% vs. 46%). Most (78%) SSPs reported optimal implementation of cabotegravir + rilpivirine LA in their clinics was achieved in 1-3 months. In interviews, SSP-reported strategies for successful implementation included teamwork, using a web-based treatment planner and having a designated person to track appointment scheduling. In month 12 interviews, SSP-reported structural changes needed for implementation included changing clinic hours and purchasing refrigerators. CONCLUSIONS: In CUSTOMIZE, cabotegravir + rilpivirine LA was successfully implemented across a range of US healthcare settings. Barriers were mitigated with minor process adjustments.

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy.

OBJECTIVES: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). DESIGN: A Phase 2b, multicenter, open-label, rollover study. METHODS: LATTE participants with plasma HIV-1 RNA less than 50 copies/ml who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50 copies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200 copies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. RESULTS: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50 copies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% (n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. CONCLUSION: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.

Perspectives of people living with HIV-1 on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings: results from the CUSTOMIZE hybrid III implementation-effectiveness study.

INTRODUCTION: The CUSTOMIZE hybrid III implementation-effectiveness study evaluated implementation of once-monthly long-acting (LA) cabotegravir + rilpivirine in diverse US healthcare settings. Here, we report patient participant perspectives after 12 months in CUSTOMIZE. METHODS: CUSTOMIZE was a phase IIIb, 12-month study conducted from July 2019 to October 2020 at eight diverse US HIV clinics that enrolled virologically suppressed people living with HIV-1 (PLHIV) on a stable oral regimen to receive monthly cabotegravir + rilpivirine LA injections after a 1-month oral lead-in. Participants were administered quantitative surveys before injections at months 1 (baseline), 4 and 12. A randomly selected subset of participants was interviewed at baseline and month 12. Data collection at month 12 was completed by October 2020 (during the COVID-19 pandemic). RESULTS: At baseline, 109 and 34 participants completed surveys and interviews, respectively; 87% were male; 35% were Black or African American. All participants who remained in the study at month 12 (n = 102) maintained HIV-1 RNA <50 copies/ml; two participants withdrew due to injection-related reasons. Mean total scores measuring acceptability and appropriateness of cabotegravir + rilpivirine LA were high at baseline (4.5-4.6 out of 5) and month 12 (4.7-4.9). At month 12, 74% of participants reported nothing interfered with receiving LA injections; injection pain or soreness was the most common concern (15%). Time spent in the clinic and coming to the clinic for monthly injections was very or extremely acceptable after 12 months for most participants (93% and 87%, respectively), with 64% reporting having spent ≤30 minutes in the clinic for injection visits. At month 12, 92% of participants preferred LA injections to daily oral tablets (3%); 97% plan to continue LA treatment going forward. In month 12 interviews, 24 (77%) of 31 participants reported the COVID-19 pandemic did not impact their ability to receive treatment. CONCLUSIONS: Once-monthly cabotegravir + rilpivirine LA was highly acceptable among PLHIV who were virologically suppressed on a stable antiretroviral regimen and interested in trying LA therapy, with few participants reporting challenges receiving LA injections. Implementation data from CUSTOMIZE suggest that monthly LA injections provide a convenient and appealing treatment option for PLHIV.

Asthma that is not well-controlled is associated with increased healthcare utilization and decreased quality of life.

BACKGROUND: Relationships of asthma control to other asthma outcomes have been incompletely documented. OBJECTIVE: This study examined the relationship between asthma control and health-related quality of life (HRQL) and subsequent healthcare resource utilization. METHODS: A 1-year online prospective longitudinal survey was conducted in 497 adults and 170 children with asthma treated in the past year. Control was measured by Asthma Control Test™ (ACT) and Childhood ACT™ (C-ACT)™ scores dichotomized into "well-controlled" (scores >19) or "not well-controlled" (scores ≤19), and HRQL was measured using the PedsQL™ 3.0 Asthma Module (children) and the SF-12 Health Survey (adults). Multivariate models were used for analysis. RESULTS: HRQL scores were significantly lower for adults (mean decrease 3.4) and children (mean decrease 12.8) whose asthma was not well-controlled compared to patients with well-controlled asthma. Adults with asthma that was not well-controlled at baseline had a threefold greater risk of an asthma-related doctor visit and a 10-fold greater risk of an emergency department (ED) visit for asthma in the subsequent 9 months (odds ratio (OR) = 3.3 and OR = 11.3, respectively). Children with asthma that was not well-controlled had a nearly fivefold increased risk for subsequent asthma-related doctors' and ED visits (OR = 4.8 and OR = 4.9, respectively). CONCLUSION: Both adults and children with not well-controlled asthma had significantly lower quality of life and were more likely to require an office or ED visit for asthma compared to patients with higher ACT scores. Therefore, it is important to continually assess asthma control and adjust controller therapy accordingly.

Retrospective analysis of adherence to HIV treatment and healthcare utilization in a commercially insured population.

AIMS: Single-tablet regimens (STRs) can improve antiretroviral therapy (ART) adherence; however, the relationship between long-term adherence and patient healthcare resource utilization (HRU) is unclear. The objective of this study was to assess long-term ART adherence among people living with HIV (PLHIV) using STRs and multi-tablet regimens (MTRs) and compare HRU over time by adherence. MATERIALS AND METHODS: This retrospective study analyzed medical and pharmacy claims (Optum Clinformatics Data Mart Database). Included PLHIV were aged ≥18 years, had ≥1 medical claim with an HIV diagnosis, and had pharmacy claims for a complete STR or MTR. Adherence was analyzed as the proportion of days covered (PDC), stratified as ≥95%, very high; 90-95%, high; 80-90%, moderate; <80%, low. Cumulative all-cause and HIV-related HRU were calculated across 4 years. Among PLHIV with ≥4-year follow-up, HRU was assessed by adherence. RESULTS: Among 15,153 PLHIV included, 63% achieved PDC ≥90% during Year 1. Among the subgroup of PLHIV with ≥4-year follow-up (N = 3,818), the proportion maintaining PDC ≥90% fell from 67% in Year 1 to 54% by Year 4. The difference from Years 1 to 4 in the proportion of PLHIV with PDC ≥90% was 13% and 17% in the STR and MTR groups, respectively. Cumulative HRU across the 4-year follow-up was higher in PLHIV with low vs high adherence (27% with low adherence had ≥1 emergency room visit vs 17% for very high, p < .0001; 15% with low adherence had ≥1 inpatient stay vs 7% for very high, p < .0001). CONCLUSIONS: ART adherence showed room for improvement, particularly over the long term. PLHIV receiving STRs exhibited higher adherence vs those receiving MTRs; this difference increased over time. The proportion of PLHIV with higher HRU was significantly higher among those with lower adherence and became greater over time. Interventions and alternative therapies to improve adherence among PLHIV should be explored.

Qualitative Thematic Analysis of Social Media Data to Assess Perceptions of Route of Administration for Antiretroviral Treatment among People Living with HIV.

BACKGROUND: HIV is a condition that requires lifelong treatment. Treatment options currently consist of oral antiretroviral therapies (ART) taken once or twice daily. Long-acting injectable HIV treatments are currently in development to be administered monthly or every other month. Preferences for route of administration could influence treatment adherence, which could affect treatment outcomes. The purpose of this study was to examine patient perceptions of oral and injectable routes of administration for ART. METHODS: Qualitative thematic analysis was conducted to examine 5122 online discussion threads by people living with HIV (PLHIV) in the POZ Community Forums from January 2013 to June 2018. Analysis focused on identifying perceptions of oral or injectable routes of administration for ART. Relevant threads were extracted and imported into the qualitative data analysis software package ATLAS.ti.8 so that text could be reviewed and coded. RESULTS: Analyses identified 684 relevant discussion threads including 2626 coded quotations from online posts by 568 PLHIV. The oral route of administration was discussed more frequently than injectable (2516 quotations for oral; 110 injectable). Positive statements on the oral route of administration commonly mentioned the small number of pills (276 quotations), dose frequency (245), ease of scheduling (153), and ease of use (146). PLHIV also noted disadvantages of the oral route of administration including negative emotional impact (166), difficulty with medication access (106), scheduling (131), and treatment adherence (121). Among the smaller number of PLHIV discussing injectable ART, common positive comments focused on dose frequency (34), emotional benefits of not taking a daily pill (7), potential benefits for adherence (6), overall convenience (6), and benefits for traveling (6). Some comments from PLHIV perceived the frequency of injections negatively (10), and others had negative perceptions of needles (8) or appointments required to receive injections (7). CONCLUSIONS: Qualitative analysis revealed that route of administration was frequently discussed among PLHIV on this online forum. While many expressed positive views about their daily oral medication regimen, others perceived inconveniences and challenges. Among PLHIV who were aware of a possible monthly injectable treatment, many viewed this new route of administration as a convenient alternative with potential to improve adherence.

Virologic Outcomes Among ART-Naïve Individuals Initiating Dolutegravir, Elvitegravir, Raltegravir or Darunavir: An Observational Study.

INTRODUCTION: Dolutegravir (DTG), Elvitegravir (EVG), Raltegravir (RAL) and Darunavir (DRV) are commonly prescribed core agents for antiretroviral therapy (ART), and a need exists to compare their clinical effectiveness, as defined by virologic failure risks in real-world settings. METHODS: This observational analysis of a US clinical cohort consisted of ART-naïve people living with HIV (PLWH) in the OPERA database initiating DTG-, EVG-, RAL- or DRV-based regimens between August 2013 and July 2016, with follow-up to July 2017. PLWH were observed from first core agent initiation until core agent discontinuation, clinical activity cessation, death, or study end. Key outcomes included viral suppression (HIV RNA < 50 copies/mL) and confirmed virologic failure (two consecutive viral loads > 200 copies/mL or a viral load > 200 copies/mL followed by discontinuation). Association between core agent and time to virologic failure was assessed with multivariate Cox proportional hazards models. RESULTS: Overall, 4049 ART-naïve PLWH initiated EVG (47.4%), DTG (34.7%), DRV (14.6%), or RAL (3.2%). DTG and EVG initiators had generally similar baseline demographics and clinical characteristics, including race, risk of infection, baseline viral load, and baseline CD4 levels. RAL and DRV initiators were older and generally sicker than DTG initiators. During follow-up, more DTG initiators achieved virologic suppression (78.7%) compared with EVG (73.6%; p < 0.05), RAL (51.9%; p < 0.0001) and DRV (48.6%; p < 0.0001) initiators. Compared to DTG, both RAL and DRV were associated with higher rates of virologic failure, with adjusted hazard ratios (95% confidence interval) of 4.70 (3.03, 7.30) and 2.38 (1.72, 3.29), respectively. No difference was observed between EVG and DTG with an adjusted hazard ratio of 1.24 (0.94, 1.64). CONCLUSION: In this large cohort representative of PLWH in care in the US, ART-naïve PLWH prescribed DTG had better virologic outcomes than RAL and DRV, but had virologic failure risks comparable to EVG, although RAL and DRV were preferentially prescribed to sicker individuals. FUNDING: ViiV Healthcare.

Real-World Experience with Dolutegravir-Based Two-Drug Regimens.

BACKGROUND: Dolutegravir-based 2-drug regimens (DTG 2DRs) are now accepted as alternatives to 3-drug regimens for HIV antiretroviral treatment (ART); however, literature on physician drivers for prescribing DTG 2DR is sparse. This study evaluated treatment patterns of DTG 2DR components in clinical practice in the US. METHODS: This was a retrospective chart review in adult patients in care in the US with HIV-1 who received DTG 2DR prior to July 31, 2017, with follow-up until January 30, 2018. Primary objectives of the study were to determine reasons for patients initiating DTG 2DR and to describe the demographics and clinical characteristics. All analyses were descriptive. RESULTS: Overall, 278 patients received DTG 2DR (male: 70%; mean age: 56 years). Most patients were treatment experienced (98%), with a mean 13.5 years of prior ART. DTG was most commonly paired with darunavir (55%) or rilpivirine (27%). The most common physician-reported reasons for initiating DTG 2DR were treatment simplification/streamlining (30%) and avoidance of potential long-term toxicities (20%). Before starting DTG 2DR, 42% of patients were virologically suppressed; of those, 95% maintained suppression while on DTG 2DR. Of the 50% of patients with detectable viral load before DTG 2DR, 79% achieved and maintained virologic suppression on DTG 2DR during follow-up. There were no virologic data for 8% of patients prior to starting DTG 2DR. Only 15 patients discontinued DTG 2DR, of whom 4 (27%) discontinued due to virologic failure. CONCLUSIONS: Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates.

Substantial decline in heavily treated therapy-experienced persons with HIV with limited antiretroviral treatment options.

OBJECTIVE: Historically, a high burden of resistance to antiretroviral therapy (ART) in heavily treatment-experienced (HTE) persons with HIV (PWH) resulted in limited treatment options (LTOs). We evaluated the prevalence, risk factors, and virologic control of HTE PWH with LTO throughout the modern ART era. DESIGN: We examined all ART-experienced PWH in care between 2000 and 2017 in the Centers for AIDS Research Network of Integrated Clinical Systems cohort. METHODS: We computed the annual prevalence of HTE PWH with LTO defined as having two or less available classes with two or less active drugs per class based on genotypic data and cumulative antiretroviral resistance. We used multivariable Cox proportional hazards models to examine risk of LTO by 3-year study entry periods adjusting for demographic and clinical characteristics. RESULTS: Among 27 133 ART-experienced PWH, 916 were classified as having LTO. The prevalence of PWH with LTO was 5.2-7.5% in 2000-2006, decreased to 1.8% in 2007, and remained less than 1% after 2012. Persons entering the study in 2009-2011 had an 80% lower risk of LTO compared with those entering in 2006-2008 (adjusted hazard ratio 0.20; 95% confidence interval: 0.09-0.42). We found a significant increase in undetectable HIV viral loads among PWH ever classified as having LTO from less than 30% in 2001 to more than 80% in 2011, comparable with persons who never had LTO. CONCLUSION: Results of this large multicenter study show a dramatic decline in the prevalence of PWH with LTO to less than 1% with the availability of more potent drugs and a marked increase in virologic suppression in the current ART era.

Comparison of corticosteroid nasal sprays in relation to concomitant use and cost of other prescription medications to treat allergic rhinitis symptoms: retrospective cohort analysis of pharmacy claims data.

BACKGROUND AND OBJECTIVE: Intranasal corticosteroids are considered to be highly effective in patients with perennial or seasonal allergic rhinitis. Multiple intranasal corticosteroid products are available; however, an intranasal corticosteroid that treats nasal and ocular seasonal allergic rhinitis symptoms may be more cost effective by reducing the need for concomitant drugs. The purpose of this study was to compare the utilization and costs of concomitant allergic rhinitis drugs among commonly used branded intranasal corticosteroid drugs. METHODS: Pharmacy claims data between 1 April 2006 and 31 January 2008 were obtained from the Wolters Kluwer SourceLx dataset. Patients with at least one pharmacy claim for a branded intranasal corticosteroid agent (fluticasone furoate, budesonide, mometasone or triamcinolone) during the index period of 1 April 2007 through 31 July 2007 were included. Study outcomes assessed were time to concomitant use of prescription allergic rhinitis drugs (other than intranasal corticosteroids) and costs of those medications and intranasal corticosteroid drugs during a 60-day post-index period. RESULTS: A total of 793 349 patients were included in the study. At index, a majority of the patients were using mometasone (62.9%), followed by triamcinolone (21.1%), budesonide (15.1%) and fluticasone furoate (1.0%). After controlling for other covariates, patients receiving fluticasone furoate had on average a 21% lower risk of concomitant prescription allergic rhinitis drug use (adjusted hazard ratio [HR] 0.79; 95% CI 0.75, 0.83) compared with the other three branded intranasal corticosteroid agents. Compared with fluticasone furoate, all other branded intranasal corticosteroid agents incurred statistically significant higher costs of concomitant allergic rhinitis drugs (6.3%, p = 0.002), resulting in increased costs to health plans of $US5-$US6 per patient over a 60-day period. Mean intranasal corticosteroid costs per patient during the 60-day follow-up period were lowest for budesonide ($US70.15), followed by fluticasone furoate ($US70.86), triamcinolone ($US73.23) and mometasone ($US75.48). CONCLUSION: In this cohort of intranasal corticosteroid users, fluticasone furoate was shown to reduce the need for concomitant prescription allergic rhinitis medications compared with other leading branded intranasal corticosteroid therapies, resulting in lower costs per patient and potentially leading to significant savings for health plans.

Evaluation of sex differences of fosamprenavir (with and without ritonavir) in HIV-infected men and women.

PURPOSE: Recent studies focusing on HIV-1-infected women have suggested the existence of sex-related differences in natural history, antiretroviral pharmacokinetics, efficacy, and tolerability. This article analyzes three pivotal trials of the protease inhibitor (PI) fosamprenavir (FPV) with a view to providing a better understanding of potential sex differences in efficacy and safety. METHOD: A post hoc, descriptive analysis was performed on data from 700 subjects (26% women) in three trials of FPV to evaluate sex differences with regard to efficacy, rates of discontinuation, and treatment-related adverse events. RESULTS: No major sex differences were found. Men and women had similarly good antiviral responses, with greater than 60% of treatment-naïve subjects achieving virologic suppression (<400 copies/mL) at 48 weeks. PI-experienced women in CONTEXT receiving once-daily FPV/r experienced the highest rates of discontinuations due to virologic failure (29% in women vs. 8% in men). Women generally had slightly lower rates of liver enzyme elevations and fewer abnormalities of total cholesterol and triglycerides. CONCLUSION: The absence of major sex differences provides reassurance, but the small number of women in these trials limited the ability to draw conclusions. Future trials should be specifically powered to detect sex differences in safety and efficacy.

Long-term (120-Week) antiviral efficacy and tolerability of fosamprenavir/ritonavir once daily in therapy-naive patients with HIV-1 infection: an uncontrolled, open-label, single-arm follow-on study.

BACKGROUND: In the SOLO study (APV30002), once-daily antiretroviral treatment with the protease inhibitor fosamprenavir (FPV) 1,400 mg boosted by ritonavir (r) 200 mg plus abacavir/lamivudine (ABC/3TC) was found to be noninferior to nelfinavir plus ABC/3TC over 48 weeks in treatment-naive patients with HIV -1 infection. OBJECTIVE: This interim report presents antiviral efficacy and tolerability data from 211 patients who received FPV/r QD for at least 48 weeks in SOLO and continued this treatment in the follow-on study (APV30005) for up to 120 weeks. METHODS: APV30005 is an international, multicenter, uncontrolled, open-label, follow-on study conducted to provide continued access to FPV in patients with HIV-1 infection who had participated in previous FPV studies, including SOLO, and to obtain longer-term data on the antiviral response and tolerability of an FPV-containing regimen. Patients who had completed at least 48 weeks of FPV/r therapy in the SOLO study were eligible to enter the follow-on study and continue receiving FPV/r 1,400/200 QD, with study visits every 12 weeks. Their background regimens were chosen at the investigators' discretion and could be changed at any time. Antiviral response end points included plasma HIV-1 RNA levels <400 and <50 copies/mL, median plasma HIV-1 RNA levels, median and absolute changes from baseline in the CD4 cell count, and the frequency of HIV disease progression. Genotype and phenotype analyses were performed for patients meeting the criterion for virologic failure (defined as plasma HIV -1 RNA >1,000 copies/mL on 2 consecutive occasions on or after week 12). Tolerability was assessed in terms of adverse-event reports evaluated by the primary investigator and changes in laboratory values. Assessments were conducted at 12-week intervals during the follow-on study. Data from the baseline visit (day 1 of SOLO) were compared with data from the follow-on study through March 31, 2004, when all patients had completed at least 120 weeks of therapy with FPV/r QD. Because this was a rollover study, no significance testing was performed and all reported results are descriptive. RESULTS: The demographic and baseline characteristics of the patients who received FPV/r QD in this follow on study (N = 211) were similar to those of the 322 patients randomized to receive FPV/r QD in the SOLO study. Their median age was 36 years, 72% were male, 49% were white, and 39% were black. The median baseline plasma HIV 1 RNA level was 4.82 log(10) copies/ mL, and the median baseline CD4+ cell count was 168 cells/mm(3). The median duration of exposure to FPV/r QD from SOLO baseline through the cutoff date was 996 days (142 weeks), ranging from 372 to 1,226 days (53-175 weeks). At week 120, plasma HIV-1 RNA levels <400 and <50 copies/mL were achieved and maintained in 75% (159) and 66% (139) of patients, respectively, when missing data and discontinuations were counted as failures. The median CD4+ cell count at week 120 was 451 cells/mm(3), a median change from baseline of 292 cells/mm(3). In 14 patients with no baseline resistance who met the criterion for virologic failure, no viral protease resistance mutations were detected. Extended treatment was generally well tolerated. The most frequently reported drug-related grade 2-4 adverse events were diarrhea (22 [10%]), nausea (17 [8%]), drug hypersensitivity (14 [7%], all cases attributed to ABC, which was a study drug in SOLO), and increased triglycerides (14 [7%]). The nature of adverse events reported after 48 weeks of therapy was comparable to that reported before week 48. Adverse events occurred at a similar or lower frequency between weeks 48 and 120 compared with before week 48. Similarly, laboratory abnormalities seen by week 120 were comparable to those seen by week 48, although they were less frequent. CONCLUSIONS: Extended treatment (120 weeks) with FPV/r QD in these antiretroviral therapy-naive, HIV-1-infected patients was associated with sustained antiviral response and immunologic improvement. Adverse events had generally developed by 48 weeks of therapy and did not occur at a higher frequency through 120 weeks of treatment.

Prospective Validation of the Lupus Impact Tracker: A Patient-Completed Tool for Clinical Practice to Evaluate the Impact of Systemic Lupus Erythematosus.

OBJECTIVE: To evaluate the reliability, validity, responsiveness, and utility of the Lupus Impact Tracker (LIT). METHODS: This was a prospective longitudinal study with 20 North American sites participating. Consenting patients completed the LIT, Medical Outcomes Study Short Form 36 (version 2), Patient Health Questionnaire 9 (PHQ-9), LupusQoL, and patient LIT feedback questionnaire. Rheumatologists completed the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and physician LIT feedback questionnaire. The reliability, convergent validity, construct validity, and responsiveness of the LIT were evaluated. RESULTS: Of the 325 SLE patients enrolled, 90% were female, 53% were white, and 33% were African American. Their mean age was 42 years. The mean ± SD baseline physician's global assessment and total SELENA-SLEDAI scores were 1.04 ± 0.8 and 4.28 ± 3.8, respectively, while 3-month scores were 0.94 ± 0.73 and 4.09 ± 3.79, respectively. Internal consistency reliability was high (>0.9) at both visits. LIT scores correlated highly with other measures of patient-reported outcomes, and construct validity was established against clinical measures. The LIT was highly responsive to patient-reported changes in SLE health status; however, LIT scores were not as responsive to changes in the SELENA-SLEDAI score. The majority of patients and physicians found LIT to be acceptable and feasible to administer in a clinical setting. CONCLUSION: The LIT is a reliable and valid instrument for assessing the impact of SLE on patients and captures unique and important information not included in physician assessments of disease. It may be useful in clinical practice to facilitate communication between the physician and the patient and enable efficient incorporation of the patient's perspective in disease management.

SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir /ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients.

OBJECTIVE: To compare the magnitude and durability of the antiviral response to fosamprenavir (FPV) plus ritonavir (RTV) once-daily (FPV/r QD) with nelfinavir twice-daily (NFV BID), each administered with abacavir and lamivudine twice-daily. METHODS: An international, phase III, randomized, open-label study in antiretroviral therapy-naive, HIV-infected adults. RESULTS: Patients with advanced HIV disease received FPV/r QD (n = 322) or NFV BID (n = 327). At week 48, 69% of patients in the FPV/r QD group and 68% in the NFV BID group had plasma HIV-1 RNA (vRNA) < 400 copies/ml, whereas 55% of patients in the FPV/r QD group and 53% in the NFV BID group had vRNA < 50 copies/ml (intent to treat, rebound/discontinuation = failure). More patients in the NFV BID group (17%) experienced virological failure than in the FPV/r QD group (7%). Efficacy of FPV/r QD was maintained in patients with CD4+ cell counts < 50 x 10 cells/l or vRNA >/= 100 000 copies/ml at entry. At week 48, median CD4+ cell counts were increased to 203 x 10 cells/l (FPV/r QD group) and 207 x 10 cells/l (NFV BID group). Both regimens were generally well tolerated. Diarrhea was more common on NFV BID than on FPV/r QD (16 versus 9%; P = 0.008). Fasting lipid profile results were generally favorable in both treatment arms. FPV/r QD maintained plasma amprenavir (APV) trough concentrations above the mean phenotypic drug-susceptibility (IC50) for wild-type virus for APV. CONCLUSION: As a first choice protease inhibitor with a low daily pill burden, FPV/r QD was well tolerated and provided potent, durable antiviral suppression.