Cost-effectiveness of Cabotegravir Long-Acting for HIV Pre-exposure Prophylaxis in the United States.

OBJECTIVE: Cabotegravir long-acting (CAB-LA) administered every 2 months was approved in the USA as pre-exposure prophylaxis (PrEP) for individuals at risk of acquiring human immunodeficiency virus (HIV)-1 infection based on the HIV Prevention Trials Network (HPTN) 083 and HPTN 084 clinical trials, which demonstrated superior reduction in HIV-1 acquisition compared with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in men who have sex with men (MSM), transgender women (TGW), and cisgender women. A decision-analytic model was developed to assess the lifetime cost-effectiveness of initiating CAB-LA versus generic oral FTC/TDF for HIV PrEP in the USA from a healthcare sector perspective. METHODS: PrEP-eligible adults entered the Markov model receiving CAB-LA or FTC/TDF and could continue initial PrEP, transition to a second PrEP option, or discontinue PrEP over time. Efficacy was taken from the HPTN 083 and HPTN 084 clinical trials. Individuals who acquired HIV-1 infection incurred lifetime HIV-related costs, could transmit HIV onwards, and could develop PrEP-related resistance mutations. Input parameter values were obtained from public and published sources. Model outcomes were discounted at 3%. RESULTS: The model estimated that the CAB-LA pathway prevented 4.5 more primary and secondary HIV-1 infections per 100 PrEP users than the oral PrEP pathway, which yielded 0.2 fewer quality-adjusted life-years (QALYs) lost per person. Additional per-person lifetime costs were $9476 (2022 US dollars), resulting in an incremental cost-effectiveness ratio of $46,843 per QALY gained. Results remained consistent in sensitivity and scenario analyses, including in underserved populations with low oral PrEP usage. CONCLUSIONS: Our analysis suggests that initiating CAB-LA for PrEP is cost-effective versus generic daily oral FTC/TDF for individuals at risk of acquiring HIV-1 infection.

Real-World Effectiveness of Dolutegravir/Lamivudine in People With HIV-1 in Test-and-Treat Settings or With High Baseline Viral Loads: TANDEM Study Subgroup Analyses.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) was first approved by the US Food and Drug Administration in 2019 for the treatment of antiretroviral therapy (ART)-naive people with HIV-1 based on results from the pivotal GEMINI-1/GEMINI-2 trials. Around that time, immediate initiation of treatment upon diagnosis was recommended in the US Department of Health and Human Services guidelines. Here we report results from 126 treatment-naive people with HIV-1 who initiated DTG/3TC as part of a test-and-treat strategy (n = 61) or with high baseline viral loads (HIV-1 RNA ≥ 100,000 copies/ml; n = 16) from the TANDEM study. METHODS: TANDEM was a US-based, retrospective chart review study that included a cohort of 126 individuals aged ≥ 18 years with no prior history of ART who initiated DTG/3TC before September 30, 2020, and had ≥ 6 months of follow-up. Test-and-treat was defined as ART initiation shortly after diagnosis without available viral load, CD4 + cell count, or HIV-1 resistance data. Outcomes included virologic suppression (HIV-1 RNA < 50 copies/ml; overall and by baseline viral load) and discontinuations. Analyses were descriptive. RESULTS: Among 61 individuals who initiated DTG/3TC in a test-and-treat setting (median [interquartile range (IQR)] treatment duration, 1.3 [0.9-1.7] years), 57 (93%) achieved virologic suppression, and 51 (84%) remained suppressed; 1 (< 1%) individual discontinued DTG/3TC due to persistent low-level viremia. The most common healthcare provider (HCP)-reported reason for initiating DTG/3TC was avoidance of long-term toxicities among individuals in the test-and-treat subgroup. Of 16 treatment-naive individuals with high baseline viral loads (median [IQR] treatment duration, 100,000-250,000 copies/ml: 1.2 [0.8-1.8] years; > 250,000 copies/ml: 1.0 [0.7-1.1] years), 14 (88%) achieved virologic suppression, 13 (81%) remained suppressed, and none discontinued DTG/3TC. Patient preference was the most common HCP-reported reason for initiating DTG/3TC in this subgroup. CONCLUSIONS: Results demonstrate real-world effectiveness of DTG/3TC, with few discontinuations, in people with HIV-1 in test-and-treat settings or with high baseline viral loads.

Two-Drug Regimens Dolutegravir/Lamivudine and Dolutegravir/Rilpivirine Are Effective with Few Discontinuations in US Real-World Settings: Results from the TANDEM Study.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA. METHODS: TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3 months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described. RESULTS: Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued. CONCLUSION: Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials.

Validity of the FACT Hepatobiliary (FACT-Hep) questionnaire for assessing disease-related symptoms and health-related quality of life in patients with metastatic pancreatic cancer.

PURPOSE: Evaluate reliability and validity of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire and its derivative FACT Hepatobiliary Symptom Indexes (FHSI-18 and FHSI-8) in people with metastatic pancreatic cancer. METHODS: Self-reported questionnaire data from a randomized controlled Phase II study evaluating the efficacy and safety of conatumumab (AMG 655), ganitumab (AMG 479) or placebo combined with gemcitabine were evaluated. The following were assessed: internal consistency, using Cronbach's α; discriminant validity, comparing baseline patient-reported outcomes (PRO) scores across Eastern Cooperative Oncology Group (ECOG) performance status (PS) levels; and ability to detect change, comparing change from baseline PRO score at each cycle across PS and tumour response groups. RESULTS: The analysis included 96 patients. All scale scores demonstrated good internal consistency (Cronbach's α > 0.7) and discriminant validity. Baseline scores were significantly poorer among patients with PS = 1 versus patients with PS = 0 (e.g. difference in FACT-Hep total score -17.27; p < 0.001). Ability to detect change was established for Cycles 2/3 versus baseline; PRO scores reduced in the PS-worsened group versus the PS-stable group (e.g. difference in FACT-Hep total score -24.29; p < 0.001). All PRO scale scores showed significant decline for progressive disease versus stable disease (e.g. difference in FACT-Hep total score -12.58; p = 0.004). Changes on the FHSI-18 and FHSI-8 scales were similar in magnitude whether ECOG improved or worsened. CONCLUSIONS: FACT-Hep detects change and is a reliable and valid instrument for measuring health-related quality of life in patients with metastatic pancreatic cancer.

Comparing Real-World Healthcare Costs Associated with Single-Tablet Regimens for HIV-1: The 2-Drug Regimen Dolutegravir/Lamivudine vs. Standard 3- or 4-Drug Regimens.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) is a 2-drug regimen for HIV-1 treatment with long-term efficacy and good tolerability comparable to 3- or 4-drug regimens. This study evaluated DTG/3TC cost versus other standard single-tablet regimens during its first year of approval. METHODS: This retrospective study analyzed US claims data from adults with HIV-1. Eligibility criteria included ≥ 1 dispensing of DTG/3TC, DTG/abacavir (ABC)/3TC, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF, and darunavir (DRV)/COBI/FTC/TAF (index date was first dispensing) and ≥ 6 months of continuous eligibility before index date (baseline period). All-cause and HIV-related healthcare costs were evaluated during the observation period (index date until earliest of end of continuous eligibility or data availability). Adjusted cost differences and adjusted cost ratios were estimated using multivariable regression models controlling for differences in baseline characteristics between cohorts. RESULTS: Overall, 22,061 individuals with HIV-1 and dispensed treatment with DTG/3TC (n = 590), DTG/ABC/3TC (n = 4355), BIC/FTC/TAF (n = 9068), EVG/COBI/FTC/TAF (n = 7081), or DRV/COBI/FTC/TAF (n = 967) were included. Most claims data were from men (mean age ~ 46 years). Mean unadjusted all-cause total healthcare costs per patient per month were significantly lower for DTG/3TC versus BIC/FTC/TAF and DRV/COBI/FTC/TAF, and mean unadjusted HIV-related healthcare costs per patient per month were significantly lower for DTG/3TC versus DRV/COBI/FTC/TAF. Cost differences were primarily driven by significantly lower pharmacy costs for DTG/3TC versus other regimens (P < 0.001), while medical costs were similar across cohorts. Results were similar among treatment-naive and treatment-experienced individuals. After adjusting for baseline covariates, significant adjusted cost differences were generally consistent with unadjusted findings. Adjusted cost ratios generally favored DTG/3TC for all-cause healthcare and HIV-related costs, with all pharmacy cost ratios favoring DTG/3TC (P < 0.001). CONCLUSION: Dolutegravir/lamivudine had the lowest healthcare costs of BIC/FTC/TAF, EVG/COBI/FTC/TAF, and DRV/COBI/FTC/TAF, and the lowest pharmacy costs of all regimens, in unadjusted and adjusted analyses and by treatment experience, supporting the economic benefits of DTG/3TC as an initial or switch regimen for HIV-1.

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.

Cost-effectiveness and budget impact of dolutegravir/lamivudine for treatment of human immunodeficiency virus (HIV-1) infection in the United States.

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

Virologic Outcomes Among People Living With Human Immunodeficiency Virus With High Pretherapy Viral Load Burden Initiating on Common Core Agents.

BACKGROUND: People living with human immunodeficiency virus (PLWH) initiating antiretroviral therapy (ART) with viral loads (VLs) ≥100 000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. METHODS: ART-naive PLWH with VLs ≥100 000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) between 12 August 2013 and 31 July 2017 were identified from the OPERA database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART; (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks; (iii) 2 consecutive VLs ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks; or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modeling estimated the association between regimen and virologic failure. RESULTS: There were 2038 ART-naive patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%), or RAL (2%). Median follow-up was 18.1 (interquartile range, 12.4-28.9) months. EVG and DTG initiators were similar at baseline, but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL, and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% confidence interval) was 1.46 (1.05-2.03) for EVG, 2.24 (1.50-3.34) for DRV, and 4.13 (1.85-9.24) for RAL. CONCLUSIONS: ART-naive PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL, and DRV initiators.Antiretroviral therapy-naïve people living with HIV (PLWH) initiating therapy with viral loads ≥100,000 copies/mL varied markedly at baseline. In adjusted models, PLWH initiating dolutegravir-based regimens were less likely to experience virologic failure as compared to elvitegravir, raltegravir and darunavir initiators.

Estimating HIV Management and Comorbidity Costs Among Aging HIV Patients in the United States: A Systematic Review.

BACKGROUND: As life expectancy of patients infected with human immunodeficiency virus (HIV) approaches that of the general population, the composition of HIV management costs is likely to change. OBJECTIVES: To (a) review treatment and disease management costs in HIV, including costs of adverse events (AEs) related to antiretroviral therapy (ART) and long-term toxicities, and (b) explore the evolving cost drivers. METHODS: A targeted literature review between January 2012 and November 2017 was conducted using PubMed and major conferences. Articles reporting U.S. costs of HIV management, acquired immunodeficiency syndrome (AIDS)-defining events, end of life care, and ART-associated comorbidities such as cardiovascular disease (CVD), chronic kidney disease (CKD), and osteoporosis were included. All costs were inflated to 2017 U.S. dollars. A Markov model-based analysis was conducted to estimate the effect of increased life expectancy on costs associated with HIV treatment and management. RESULTS: 22 studies describing HIV costs in the United States were identified, comprising 16 cost-effectiveness analysis studies, 5 retrospective analyses of health care utilization, and 1 cost analysis in a resource-limited setting. Management costs per patient per month, including routine care costs (on/off ART), non-HIV medication, opportunistic infection prophylaxis, inpatient utilization, outpatient utilization, and emergency department utilization were reported as CD4+ cell-based health state costs ranging from $1,192 for patients with CD4 > 500 cells/mm3 to $2,873 for patients with CD4 < 50 cells/mm3. Event costs for AEs ranged from $0 for headache, pain, vomiting, and lipodystrophy to $31,545 for myocardial infarction. The mean monthly per-patient costs for CVD management, CKD management, and osteoporosis were $5,898, $6,108, and $4,365, respectively. Improvements in life expectancy, approaching that of the general population in 2018, are projected to increase ART-related and AE costs by 35.4% and comorbidity costs by 175.8% compared with estimated costs with HIV life expectancy observed in 1996. CONCLUSIONS: This study identified and summarized holistic cost estimates appropriate for use within U.S. HIV cost-effectiveness analyses and demonstrates an increasing contribution of comorbidity outcomes, primarily associated with aging in addition to long-term treatment with ART, not typically evaluated in contemporary HIV cost-effectiveness analyses. DISCLOSURES: This analysis was sponsored by ViiV Healthcare, which had no role in the analyses and interpretation of study results. Ward, Sugrue, Hayward, and McEwan are employees of HEOR Ltd, which received funding from ViiV Healthcare to conduct this study. Anderson is an employee of GlaxoSmithKline and holds shares in the company. Punekar and Oglesby are employees of ViiV Healthcare and hold shares in GlaxoSmithKline. Lopes was employed by ViiV Healthcare at the time of the study and holds shares in GlaxoSmithKline.

Retrospective analysis of comorbidities and treatment burden among patients with HIV infection in a US Medicaid population.

Objective: Comorbidities and comedications are important factors influencing optimal therapy because people are living longer with HIV infection. This study describes the long-term comorbidity profile and treatment burden among people with HIV-1 infection.Methods: This retrospective study included Medicaid claims data from patients with ≥1 antiretroviral (ARV) claim between 2016 and 2017 (most recent claim defined the index date), ≥1 HIV diagnosis within 1 year before index, age ≥18 years at first HIV diagnosis and <65 years at index, ≥12 months of continuous eligibility before index, and no history of HIV-2 infection. Comorbidities, concomitant medication use, and pill burden were assessed in the 4 years before index. Analyses were stratified by patient age and treatment experience.Results: Among 3456 patients, the mean (standard deviation [SD]) age was 47.1 (10.4) years; the majority were black (55%) and men (63%). In general, the prevalence of comorbidities increased from the fourth year to the first year before index and included cardiovascular disease (28-40%), hypertension (24-37%), hyperlipidemia (12-17%), and asthma/chronic obstructive pulmonary disease (13-19%). Concomitant medication use corresponding to these comorbidities slightly increased over time. In the year before index, mean (SD) daily pill burden was 2.1 (1.4) for ARVs and 5.9 (5.9) for non-ARVs. Older age and prior treatment experience were associated with higher rates of comorbidities and greater pill burden.Conclusions: In people with HIV infection, comorbidities and concomitant medication use increased with age, supporting considerations for streamlined ARV regimens highlighted in treatment guidelines.

Benchmarking HIV Quality Measures Across US Payer Types.

Despite advances in antiretroviral therapy (ART), human immunodeficiency virus (HIV) remains a significant issue in the United States. Early diagnosis, continuous treatment access/adherence, and long-term care engagement help patients benefit fully from ART; however, a shortfall in care engagement remains, potentially leading to poorer health outcomes. This analysis benchmarks rates of health care quality and process measures to identify areas for improvement. This retrospective, claims-based, real-world cohort study assessed the percentage of prevalent (existing) and incident (newly diagnosed) patients with HIV with commercial or public health insurance meeting 4 National Quality Forum (NQF)-endorsed, 1 Pharmacy Quality Alliance (PQA), and 3 Centers for Disease Control and Prevention (CDC) measures over a 4-year period. Most prevalent patients consistently met the NQF-endorsed prescribed ART and gaps in visits measures. Longer-term visit frequency measure rates were well below the 90% Joint United Nations Programme on HIV/AIDS target. Proportion of prevalent patients meeting each NQF-endorsed measure was maintained/increased with increasing age in 2015-2016. Substantially fewer incident patients than prevalent patients met NQF-endorsed measures across all measurement periods, particularly for visit frequency (32%-51%). PQA ART adherence was low (36%-73%). CDC receipt of care rates were high (83%-92%), whereas retention in care rates were low (67%-72%) among prevalent patients. For incident patients, linkage to care rates were consistently low (21%-44%). This study benchmarks current US HIV care engagement and highlights the need for improvement in early care engagement, ART adherence and long-term retention of care among patients with HIV.

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.

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.

Clinical characteristics and treatment patterns among US patients with HIV.

OBJECTIVES: Describe the clinical characteristics and treatment patterns of patients with HIV-1 who have commercial or Medicare health insurance in the United States. STUDY DESIGN: Retrospective cohort study. METHODS: Administrative claims for adult commercial and Medicare health plan enrollees with evidence of HIV-1 and antiretroviral therapy (ART) between January 1, 2007, and March 31, 2017, were assessed. Current and previous complete ART regimens were identified using a claims-based algorithm. Results were stratified by treatment status and insurance type. RESULTS: Of 18,699 eligible patients, 5027 (27%) had no previous ART regimens; 15,275 (82%) had commercial insurance. Mean age was 47.5 years. Common comorbidities included hyperlipidemia, cardiovascular disease, hypertension, depression, and anxiety. The mean number of ART regimens was 1.43, with 31% of patients having 2 or more regimens. Mean (SD) daily pill burden was higher in patients with more than 1 ART regimen over time (5.7 [6.0] pills) or with Medicare insurance (9.2 [8.0] pills) than in patients with no previous ART (1.9 [4.4] pills) or with commercial insurance (3.7 [4.7] pills). Overall, 60% of patients achieved 90% or greater adherence to their ART regimen and 16% had a prescription filled for any contraindicated medication to an ART during their regimen. CONCLUSIONS: This descriptive study demonstrated that people living with HIV enrolled in Medicare have a significant amount of comorbidities and total pill burden. Although advancements in ART have significantly improved life expectancy and quality of life for people living with HIV, it is important to take into account individual complexities such as comorbidities and pill burden when selecting ART regimens.

Real-World Health Plan Data Analysis: Key Trends in Medication Adherence and Overall Costs in Patients with HIV.

BACKGROUND: Adherence to effective antiretroviral therapy (ART) is essential to achieve long-term viral suppression in patients with HIV-1. Single-tablet regimens (STRs) have improved adherence and decreased health care costs and hospitalizations, but previous study results suggest that the relationship between ART adherence and health care costs and utilization is complex. OBJECTIVE: To assess ART adherence trends in patients with HIV-1 to determine if differences in utilization, demographics, and overall costs exist among patients with varying levels of medication adherence. METHODS: This retrospective study analyzed medical and pharmacy claims data from an administrative claims database between January 1, 2007, and June 30, 2016, for Medicaid or commercially insured patients continuously enrolled for ≥ 6 months before and ≥ 15 months after the index date (date of first medical claim with an HIV diagnosis or pharmacy claim for HIV ART medication between July 1, 2007, and June 30, 2014). Qualifying patients were aged ≥ 18 years with a diagnosis of HIV-1 infection or at least 1 pharmacy claim for HIV ART at index and at least 2 pharmacy claims during the follow-up period. Patients were categorized on the basis of adherence as measured by proportion of days covered (PDC; ≥ 95%, highly adherent; < 95%, less adherent) and treatment with an STR or multiple-tablet regimen (MTR). Commercially insured patients were stratified by duration of follow-up data (< 3 or ≥ 3 years). There were not enough Medicaid patients for follow-up analysis. Outcomes of interest were ART adherence and annual medical and pharmacy utilization and costs. Descriptive statistics were generated, and health care resource utilization and costs were reported as annual averages. Chi-square and t-tests were used to examine differences between the cohorts. RESULTS: A total of 332 Medicaid patients and 1,698 patients insured commercially met inclusion criteria. Adherence to ART medication (mean PDC) during the first 15 months was lower in Medicaid patients (65%) versus commercial patients (79%; P < 0.0001). Patients treated with STRs comprised 47% and 37% of patients in the < 3-year and ≥ 3-year follow-up cohorts, respectively. More STR patients achieved ≥95% adherence than MTR patients (< 3-year follow-up, 53% vs. 39%; ≥ 3-year follow-up, 61% vs. 45%; P < 0.001). In both follow-up cohorts, less adherent patients had higher mean annual medical costs, and results were significant for patients with ≥ 3-year follow-up ($8,224 vs. $3,097; P = 0.0007). These results were largely driven by savings in mean annual inpatient costs among the highly adherent patients in both cohorts (< 3-year follow-up, -$2,525 [P = 0.0003]; ≥ 3-year follow-up, -$815 [P < 0.001]). CONCLUSIONS: Patients on STRs were more adherent than patients on MTRs regardless of length of follow-up. Better adherence was associated with significant inpatient cost savings. The relationship between adherence and total medical costs is nuanced depending on the duration of follow-up. DISCLOSURES: This study was funded by ViiV Healthcare, which participated in protocol development, the analysis plan, and interpretation of results but did not have final approval on the decision to publish. Kangethe, Polson, Lord, and Evangelatos are employees of Magellan Rx Management, which was contracted by ViiV Healthcare to conduct the research for this study. Oglesby is an employee of ViiV Healthcare and owns stock in GlaxoSmithKline. Data from this study were previously presented at AMCP Nexus; October 16-19, 2017; Dallas, TX.

Estimating the long-term cost-effectiveness of exenatide in the United States: an adjunctive treatment for type 2 diabetes mellitus.

OBJECTIVES: This analysis provides an early estimate of the cost-effectiveness of adjunctive exenatide in treating type 2 diabetes mellitus in the United States. Data from pivotal phase III 30-week clinical trials and 52 weeks of their subsequent open-label extension studies (i.e., 82 weeks total) were used to project the effects of 30 years of adjunctive exenatide treatment. METHODS: This analysis utilized a published and validated Markov model incorporating Monte Carlo simulation with tracker variables to estimate the clinical and cost outcomes of adding exenatide to a background of metformin and/or sulfonylurea treatment, with the effects of 30 years of adjunctive exenatide treatment (projected from data from 82 weeks of exenatide treatment) compared with no additional treatment beyond metformin and/or a sulfonylurea. Sensitivity analyses were performed on key clinical assumptions, discount rates, and shorter time horizons. RESULTS: The base-case scenario (30 years of exenatide) yielded an incremental cost-effectiveness ratio (ICER) of $35,571. We found that shortening the time horizons and removing the lipid effects of exenatide had the greatest negative impact on ICERs when performing sensitivity analysis. CONCLUSIONS: Our analysis demonstrated that exenatide used for 20 or 30 years compared with no additional treatment beyond metformin and/or a sulfonylurea is cost-effective in the adjunctive treatment of type 2 diabetes with an ICER less than $50,000 per life-year gained. Sensitivity analyses suggest that, in addition to sustained reduction in HbA(1c), the added clinical effects of improved lipid values, systolic blood pressure, and reduced body mass index all positively contributed to the cost-effectiveness of exenatide.

The longitudinal link between visual acuity and health-related quality of life in patients with diabetic retinopathy.

BACKGROUND: This study characterized the degree of change in health-related quality of life (HRQL) associated with change in visual acuity among patients with diabetic retinopathy. METHODS: Data are from a randomized, placebo-controlled trial of ruboxistaurin for vision loss in patients with diabetic retinopathy. Visual acuity was quantified as letters on the ETDRS visual acuity chart. HRQL was assessed with the 25-Item Visual Function Questionnaire (VFQ-25) and the SF-36. Patients were categorized into groups based on visual acuity change from baseline to month 18. HRQL change of these groups was compared using general linear models. Regression analyses examined visual acuity change defined continuously. RESULTS: Patients (N = 535) were primarily Caucasian (81.9%) and male (64.1%); mean age = 59.3 years. Compared to patients whose visual acuity did not change, the group with > 10 letters vision loss had significantly greater decreases in all VFQ-25 subscales except ocular pain. SF-36 change scores did not correspond as closely to change in vision. Change in visual acuity defined continuously was significantly associated with change in all VFQ-25 scales except ocular pain (p < 0.0001). CONCLUSION: Change in visual acuity was associated with corresponding changes in HRQL among patients with diabetic retinopathy. Previous research has often defined vision loss as a loss of at least 15 letters on the ETDRS visual acuity chart. In the current study, however, a loss of at least 10 letters was associated with substantial declines in HRQL domains such as driving, dependency, role limitations, and mental health. These findings suggest that patients who experience vision loss of at least 10 letters may be appropriate targets of future research and clinical intervention.

The association between diabetes related medical costs and glycemic control: a retrospective analysis.

BACKGROUND: The objective of this research is to quantify the association between direct medical costs attributable to type 2 diabetes and level of glycemic control. METHODS: A longitudinal analysis using a large health plan administrative database was performed. The index date was defined as the first date of diabetes diagnosis and individuals had to have at least two HbA1c values post index date in order to be included in the analyses. A total of 10,780 individuals were included in the analyses. Individuals were stratified into groups of good (N = 6,069), fair (N = 3,586), and poor (N = 1,125) glycemic control based upon mean HbA1c values across the study period. Differences between HbA1c groups were analyzed using a generalized linear model (GLM), with differences between groups tested by utilizing z-statistics. The analyses allowed a wide range of factors to affect costs. RESULTS: 42.1% of those treated only with oral agents, 66.1% of those treated with oral agents and insulin, and 57.2% of those treated with insulin alone were found to have suboptimal control (defined as fair or poor) throughout the study period (average duration of follow-up was 2.95 years). Results show that direct medical costs attributable to type 2 diabetes were 16% lower for individuals with good glycemic control than for those with fair control ($1,505 vs. $1,801, p < 0.05), and 20% lower for those with good glycemic control than for those with poor control ($1,505 vs. $1,871, p < 0.05). Prescription drug costs were also significantly lower for individuals with good glycemic control compared to those with fair ($377 vs. $465, p < 0.05) or poor control ($377 vs. $423, p < 0.05). CONCLUSION: Almost half (44%) of all patients diagnosed with type 2 diabetes are at sub-optimal glycemic control. Evidence from this analysis indicates that the direct medical costs of treating type 2 diabetes are significantly higher for individuals who have fair or poor glycemic control than for those who have good glycemic control. Patients under fair control account for a greater proportion of the cost burden associated with antidiabetic prescription drugs.

Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes.

BACKGROUND: Patient-reported measures can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. Although exenatide and insulin glargine appear to have similar efficacy for treatment of type 2 diabetes, there are several differences between the two treatments that could influence outcomes from the patient's perspective. The purpose of the current study was to examine whether the two drugs were comparable as assessed by patient-reported outcomes using data from a clinical trial in which these injectable medications were added to pre-existing oral treatment regimens. METHODS: Patients were randomized to either twice daily exenatide or once daily insulin glargine during a 26-week international trial. At baseline and endpoint, five patient-reported outcome measures were administered: the Vitality Scale of the SF-36, The Diabetes Symptom Checklist - Revised (DSC-R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was analyzed within each treatment group. Group differences were examined with General linear models (GLMs), controlling for country and baseline scores. RESULTS: A total of 549 patients with type 2 diabetes were enrolled in the trial, and current analyses were conducted with data from the 455 per protocol patients (228 exenatide and 227 insulin glargine). The sample was primarily Caucasian (79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5 years. Paired t-tests found that both treatment groups demonstrated statistically significant baseline to endpoint change on several of the health outcomes instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs found no statistically significant differences between groups in change on the health outcomes instruments. CONCLUSION: This analysis found that both exenatide and insulin glargine were associated with significant improvements in patient-reported outcomes when added to oral medications among patients with type 2 diabetes. Despite an additional daily injection and a higher rate of gastrointestinal adverse events, treatment satisfaction in the exenatide group was comparable to that of the glargine group, possibly because of weight reduction observed in patients treated with exenatide.

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.