Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis.

INTRODUCTION: To compare the economic benefit of upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy from improvements in health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from two trials of upadacitinib (SELECT-NEXT and SELECT-MONOTHERAPY) and one trial of tofacitinib (ORAL-Standard) that collected HRQOL measurements using the Short Form 36 (SF-36) Health Survey in patients with RA. Direct medical costs per patient per month (PPPM) for patients receiving upadacitinib 15 mg once daily and methotrexate were derived from observed SF-36 Physical (PCS) and Mental Component Summary (MCS) scores in the SELECT trials using a regression algorithm. Direct medical costs PPPM for patients receiving tofacitinib 5 mg twice daily were obtained from a published analysis of SF-36 PCS and MCS scores observed in the ORAL-Standard trial. Short-term (12-14 weeks) and long-term (48 weeks) estimates of direct medical costs PPPM were compared between upadacitinib and tofacitinib and between upadacitinib and methotrexate. RESULTS: Over 12 weeks, direct medical costs PPPM were $252 lower (95% CI $72, $446) for upadacitinib-treated patients versus tofacitinib-treated patients. Medical costs PPPM at weeks 24 and 48 and cumulative costs over the entire 48-week period (difference $1759; 95% CI $1162, $2449) were significantly lower for upadacitinib than for tofacitinib. Over 14 weeks, direct medical costs PPPM were $399 lower (95% CI $158, $620) for patients treated with upadacitinib monotherapy compared with those treated with methotrexate alone. Direct medical costs at week 48 and cumulative costs over the entire 48-week period (difference $2044; 95% CI $1221, $2846) were significantly lower for upadacitinib monotherapy compared with methotrexate alone. CONCLUSION: In the short and long term, upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy were associated with significantly lower direct medical costs for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02675426, NCT02706951, and NCT00853385.

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.

Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines.

BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens. METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain. INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. FUNDING: Bill & Melinda Gates Foundation.

Effectiveness, Safety, and Costs of Dolutegravir/Abacavir/Lamivudine Single-Tablet Regimen in a Real-Life Cohort of HIV-1 Adult Infected Patients.

Background: Real-life data on single-tablet regimen (STR) dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) is scarce, and concerns about DTG neuropsychiatric adverse events (NP-AEs) have recently arisen. Objective: To explore the effectiveness and safety, in particular NP-AEs, of DTG/ABC/3TC in a cohort of HIV-1 adult infected patients. Pill burden, adherence to this STR, and the impact of switching on costs were also evaluated. Methods: This was an observational, retrospective study. The study population included antiretroviral therapy (ART)-naive and treatment-experienced (TE) patients who started DTG/ABC/3TC between February 1, 2016, and October 31, 2016. Effectiveness and safety were analyzed at week 48 (W48) by intention-to-treat analysis. The Cox regression model was used to investigate predictors of DTG/ABC/3TC discontinuation. Results: A total of 253 patients were included (44 ART naïve, 209 TE). At W48, the proportion of patients with virological suppression was 72.7% (95% CI = 58.4-87.0) in ART-naive patients, 85.6% (95% CI = 80.3-90.9) in previously suppressed TE patients, and 86.4% (95% CI = 65.1-97.1) in previously not suppressed TE patients. The rate of protocol-defined virological failure was 4.3%. The incidence of AEs was higher in the subgroup of ART-naive patients (56.1% vs 39.0%), with a rate of interruptions for this reason of 13.6% and 7.6%, respectively. The incidence of NP-AEs was 20.6%, with 3.9% of patients requiring discontinuation. Patients who had switched from a raltegravir-containing regimen discontinued DTG/ABC/3TC because of AEs more frequently (relative risk = 2.83; 95% CI = 1.04-7.72; P = 0.041) in the multivariate analysis. After switching to DTG/ABC/3TC, the median pill burden was reduced from 3 to 1 and the proportion of patients with an adherence <90%, from 20.1% to 12.0%. The annual per-patient ART costs increased by €48 (0.6% increase). Conclusion and Relevance: DTG/ABC/3TC is an effective strategy as first-line and switching ART. Our data suggest a worse tolerance in ART-naive patients, although the rate of discontinuation resulting from NP-AEs was relatively low. In the short-term, the adherence was slightly improved without significant changes in costs.

DOLAMA study: Effectiveness, safety and pharmacoeconomic analysis of dual therapy with dolutegravir and lamivudine in virologically suppressed HIV-1 patients.

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.

De-simplifying single-tablet antiretroviral treatments: uptake, risks and cost savings.

OBJECTIVES: As more HIV-positive individuals receive antiretroviral therapy (ART), payers are seeking options for covering these increased and sustained drug costs. Strategic use of available generic antiretroviral (ARV) formulations may be feasible. De-simplifying a single-tablet co-formulation (STF) into two or more tablets using both brand and generic drugs has been proposed. We determine if voluntary de-simplification of one STF could be utilized as a cost-saving strategy. We report on the challenges, uptake, outcomes and cost savings of this initiative. METHODS: Patients stable on the most commonly used STF (Triumeq® ) were offered the option of remaining on Triumeq® or switching to generic abacavir/lamivudine and Tivicay® between 1 January 2015 and 1 January 2018; those starting ART consisting of abacavir/lamivudine/doulutegravir in the same period were offered the option of starting Triumeq® or generic abacavir/laminvudine and Tivicay® . No incentives were provided. We examined the acceptance/decline rates, patient satisfaction, health care outcomes and annual cost savings. RESULTS: Of 626 patients receiving Triumeq® , 321 were approached; 177 (55.1%) agreed to de-simplify. Of patients initiating ART, 62.7% chose the generic co-formulation. Patients switching to or starting on the generic co-formulation were more likely to be male, > 45 years old, Caucasian, men who have sex with men (MSM) and more HIV-experienced, and to have more comorbidities (all P < 0.05). Preference for STF was cited for declining de-simplification. No concern about generic ARVs was expressed. The rate of viral load > 500 HIV-1 RNA copies/mL after baseline was 2.7% in switched patients compared with 7.0% in those declining to switch. No de novo resistance occurred. A saving of Cdn$1 319 686 was achieved in the first year. CONCLUSIONS: Reliance on altruism, while respecting patient autonomy, achieved de-simplification in > 50% of patients approached, and generated immediate cost savings with no increased risk of adverse events, viral breakthrough or resistance.

Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research.

A new first-line antiretroviral therapy (ART) regimen containing dolutegravir is being rolled out in low-income and middle-income countries (LMICs). In studies from predominantly high-income settings, dolutegravir-based regimens had superior efficacy, tolerability, and durability compared with existing first-line regimens. However, several questions remain about the roll out of dolutegravir in LMICs, where most people with HIV are women of reproductive age, tuberculosis prevalence can be high, and access to viral load and HIV drug resistance testing is limited. Findings from cohort studies suggest that dolutegravir is safe when initiated in pregnancy, but more data are needed to determine the risk of adverse birth outcomes when dolutegravir-based regimens are initiated before conception. Increasing access to viral load testing to monitor the effectiveness of dolutegravir remains crucial, but the best strategy to manage patients with viraemia is unclear. Furthermore, evidence to support the effectiveness of dolutegravir when given with tuberculosis treatment is scarce, particularly in programmatic settings in LMICs. Lastly, whether nucleoside reverse transcriptase inhibitor resistance will affect the long-term efficacy of dolutegravir-based regimens in first-line, and potentially second-line, ART is unknown. Clinical trials, cohorts, and surveillance of HIV drug resistance will be necessary to answer these questions and to maximise the benefits of this new regimen.

The transition to dolutegravir and other new antiretrovirals in low-income and middle-income countries: what are the issues?

: There are currently approximately 16 million people taking NNRTI-based first-line treatment in low-income and middle-income countries. Most of these patients are using the combination of tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV). The integrase inhibitor dolutegravir (DTG) has shown an improved safety profile compared with EFV in randomized studies. DTG also has a high barrier to development of drug resistance. New co-formulated tablets with TDF/3TC/DTG are being introduced into LMICs, for a median price of $75 per person-year. The prodrug of TDF, tenofovir alafenamide (TAF) is cheaper to manufacture than TDF. A combined pill with TAF/3TC/DTG is also being launched in LMICs, at a similar low price. However, the clinical development programmes for DTG and TAF did not include extensive analysis of several key populations: pregnant women, people with HIV-tuberculosis (TB) coinfection taking rifampicin-based treatment, and treatment-naive or pretreated patients with NRTI drug resistance. An observational study in Botswana has shown an increased risk of neural tube defects when dolutegravir is used in early pregnancy. In LMICs, only 50% of patients have access to regular viral load testing, and genotypic resistance testing is rarely performed. There is currently no clinical data to support switching patients from TDF/3TC/EFV directly to TDF/3TC/DTG if their viral load is either detectable or unknown. New clinical trials and observational studies will be needed to better understand the consequences of this switch of treatment in LMICs. Clinical trials of new antiretrovirals in key populations should be conducted earlier in their development. This will ensure that new treatments can be introduced into LMICs soon after their launch in high-income countries.

The cost-effectiveness and budgetary impact of a dolutegravir-based regimen as first-line treatment of HIV infection in India.

INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended for first-line HIV treatment in the US and Europe. Efavirenz (EFV)-based regimens remain the standard of care (SOC) in India. We examined the clinical and economic impact of DTG-based first-line ART in the setting of India's recent guidelines change to treating all patients with HIV infection regardless of CD4 count. METHODS: We used a microsimulation of HIV disease, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model, to project outcomes in ART-naive patients under two strategies: (1) SOC: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC); and (2) DTG: DTG + TDF/3TC. Regimen-specific inputs, including virologic suppression at 48 weeks (SOC: 82% vs. DTG: 90%) and annual costs ($98 vs. $102), were informed by clinical trial data and other sources and varied widely in sensitivity analysis. We compared incremental cost-effectiveness ratios (ICERs), measured in $/year of life saved (YLS), to India's per capita gross domestic product ($1600 in 2015). We compared the budget impact and HIV transmission effects of the two strategies for the estimated 444,000 and 916,000 patients likely to initiate ART in India over the next 2 and 5 years. RESULTS: Compared to SOC, DTG improved 5-year survival from 76.7% to 83.0%, increased life expectancy from 22.0 to 24.8 years (14.0 to 15.5 years, discounted), averted 13,000 transmitted HIV infections over 5 years, increased discounted lifetime care costs from $3040 to $3240, and resulted in a lifetime ICER of $130/YLS, less than 10% of India's per capita GDP in 2015. DTG maintained an ICER below 50% of India's per capita GDP as long as the annual three-drug regimen cost was ≤$180/year. Over a 2- or 5-year horizon, total undiscounted outlays for HIV-related care were virtually the same for both strategies. CONCLUSIONS: A generic DTG-based regimen is likely to be cost-effective and should be recommended for initial therapy of HIV infection in India.

Patient perspectives on de-simplifying their single-tablet co-formulated antiretroviral therapy for societal cost savings.

OBJECTIVES: The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV-infected patients are substantial, so cost-saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de-simplifying (i.e. switching) more expensive single-tablet formulations (STFs) to less expensive generic-based multi-tablet components. We determined physician and patient perceptions and acceptance of STF de-simplification within the context of a publicly funded ARV budget. METHODS: Programme costs were calculated for patients on ARVs followed at the Southern Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving Triumeq® and determined the savings if patients de-simplified to eligible generic co-formulations. We surveyed all prescribing physicians and a convenience sample of patients taking Triumeq® to see if, for budgetary purposes, they felt that de-simplification would be acceptable. RESULTS: Of 1780 patients receiving ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on Triumeq®. The total annual cost of ARVs was $26 222 760. The cost for Triumeq® was $8 292 600. If every patient on Triumeq® switched to generic abacavir/lamivudine and Tivicay® (dolutegravir), total costs would decrease by $4 325 040. All physicians (n = 13) felt that de-simplifying could be safely achieved. Forty-eight per cent of 221 patients surveyed were agreeable to de-simplifying for altruistic reasons, 27% said no, and 25% said maybe. CONCLUSIONS: De-simplifying Triumeq® generates large cost savings. Additional savings could be achieved by de-simplifying other STFs. Both physicians and patients agreed that selective de-simplification was acceptable; however, it may not be acceptable to every patient. Monitoring the medical and cost impacts of de-simplification strategies seems warranted.

Cost-effectiveness of dolutegravir/abacavir/lamivudine in HIV-1 treatment-Naive (TN) patients in France.

BACKGROUND: To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naive (TN) HIV adult patients. METHODS: The ARAMIS microsimulation Markov model, evaluates costs and effects of DTG vs. first-line ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse transcriptase inhibitors (efavirenz and rilpivirine). Efficacy and safety data were derived from phase III studies and network meta-analysis. Treatment algorithms were based on French guidelines and experts opinion. Costs included routine HIV and opportunistic infection care, and death. RESULTS: The model showed the fixed-dose combination DTG/ABC/3TC was more effective than all other recommended regimens: patients stayed longer on first-line, and lived longer and healthier. With the exception of EFV, DTG/ABC/3TC was more efficacious and less costly compared to all strategies. The cost per QALY gained (ICER) for DTG compared to EFV was €6,939. DTG/ABC/3TC was more efficacious and less costly compared to INIs and PIs in all deterministic sensitivity analyses. CONCLUSION: DTG/ABC/3TC was cost-effective in the management of HIV TN patients in France. These results are mainly explained by its lower price compared to other INIs and PIs, DTG's superior efficacy and high barrier to resistance.

Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study.

BACKGROUND: There is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high. METHODS: The HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year. FINDINGS: A transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost. INTERPRETATION: A future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance. FUNDING: Bill & Melinda Gates Foundation, World Health Organization.

The Cost-effectiveness and Budget Impact of 2-Drug Dolutegravir-Lamivudine Regimens for the Treatment of HIV Infection in the United States.

BACKGROUND: Recommended human immunodeficiency virus (HIV) treatment regimens in the United States contain 3 antiretroviral agents, costing >$30 000/person/year. Pilot studies are evaluating the efficacy of dual therapy with dolutegravir (DTG) and lamivudine (3TC). We examined the potential cost-effectiveness and budget impact of DTG + 3TC regimens in the United States. METHODS: Using a mathematical model, we projected the clinical and economic outcomes of antiretroviral therapy (ART)-naive patients under 4 strategies: (1) no ART (for modeling comparison); (2) 2-drug: initial regimen of DTG + 3TC; (3) induction-maintenance: 48-week induction regimen of 3 drugs (DTG/abacavir [ABC]/3TC), followed by DTG + 3TC maintenance if virologically suppressed; and (4) standard of care: 3-drug regimen of DTG/ABC/3TC. Strategy-dependent model inputs, varied widely in sensitivity analyses, included 48-week virologic suppression (88%-93%), subsequent virologic failure (0.1%-0.6%/month), and Medicaid-discounted ART costs ($15 200-$39 600/year). A strategy was considered cost-effective if its incremental cost-effectiveness ratio (ICER) was <$100 000/quality-adjusted life-year (QALY). RESULTS: The 3 ART strategies had the same 5-year survival rates (90%). The ICER was $22 500/QALY for induction-maintenance and >$500 000/QALY for standard of care. Two-drug was the preferred strategy only when DTG + 3TC 48-week virologic suppression rate exceeded 90%. With 50% uptake of either induction-maintenance or 2-drug for ART-naive patients, cost savings totaled $550 million and $800 million, respectively, within 5 years; savings reached >$3 billion if 25% of currently suppressed patients were switched to DTG + 3TC maintenance. CONCLUSIONS: Should DTG + 3TC demonstrate high rates of virologic suppression, this regimen will be cost-effective and would save >$500 million in ART costs in the United States over 5 years.

Cost-Effectiveness of Dolutegravir in HIV-1 Treatment-Experienced (TE) Patients in France.

OBJECTIVES: To evaluate the cost-effectiveness of a new generation integrase inhibitor (INI), dolutegravir (DTG), in France, in treatment-experienced (TE) and INI-naïve HIV-infected adults with at least two classes resistance compared to raltegravir (RAL), by adapting previously published Anti-Retroviral Analysis by Monte Carlo Individual Simulation (ARAMIS) model. METHODS: ARAMIS is a microsimulation Markov model with a lifetime time horizon and a monthly cycle length. Health states are defined as with or without opportunistic infection and death. In the initial cohort, efficacy and safety data were derived from a phase III study comparing DTG to RAL. Antiretroviral treatment algorithms, accounting for patient history, were based on French guidelines and experts opinion. Costs are mainly including treatment costs, routine HIV and opportunistic infection care, and death. Utilities depend on CD4+ cell count and the occurrence of opportunistic infections. RESULTS: The ARAMIS model indicates in the TE population that DTG compared to RAL over a life time is associated with 0.35 additional quality-adjusted life years (QALY; 10.75 versus 10.41) and additional costs of €7,266 (€390,001 versus €382,735). DTG increased costs are mainly related to a 9.1-month increase in life expectancy for DTG compared with RAL, and consequently a longer time spent on ART. The incremental cost-effectiveness ratio (ICER) for DTG compared with RAL is €21,048 per QALY gained. About 83% and 14% of total lifetime costs are associated with antiretroviral therapy and routine HIV care respectively. Univariate deterministic sensitivity analyses demonstrate the robustness of the model. CONCLUSION: DTG is cost-effective in the management of TE INI naive patients in France, from a collective perspective. These results could be explained by the superior efficacy of DTG in this population and its higher genetic barrier to resistance compared to RAL. These data need to be confirmed with longer-term real life data.

Cost-effectiveness of novel regimens for the treatment of hepatitis C virus.

BACKGROUND: New regimens for hepatitis C virus (HCV) have shorter treatment durations and increased rates of sustained virologic response compared with existing therapies but are extremely expensive. OBJECTIVE: To evaluate the cost-effectiveness of these treatments under different assumptions about their price and efficacy. DESIGN: Discrete-event simulation. DATA SOURCES: Published literature. TARGET POPULATION: Treatment-naive patients infected with chronic HCV genotype 1, 2, or 3. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Usual care (boceprevir-ribavirin-pegylated interferon [PEG]) was compared with sofosbuvir-ribavirin-PEG and 3 PEG-free regimens: sofosbuvir-simeprevir, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir. For genotypes 2 and 3, usual care (ribavirin-PEG) was compared with sofosbuvir-ribavirin, sofosbuvir-daclatasvir, and sofosbuvir-ledipasvir-ribavirin (genotype 3 only). OUTCOME MEASURES: Discounted costs (in 2014 U.S. dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7000, $5500, $5500, and $875 per week, respectively, sofosbuvir-ledipasvir was cost-effective for genotype 1 and cost $12 825 more per QALY than usual care. For genotype 2, sofosbuvir-ribavirin and sofosbuvir-daclatasvir cost $110 000 and $691 000 per QALY, respectively. For genotype 3, sofosbuvir-ledipasvir-ribavirin cost $73 000 per QALY, sofosbuvir-ribavirin was more costly and less effective than usual care, and sofosbuvir-daclatasvir cost more than $396 000 per QALY at assumed prices. RESULTS OF SENSITIVITY ANALYSIS: Sofosbuvir-ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5500. For genotype 2, sofosbuvir-ribavirin-PEG would be cost-saving if sofosbuvir cost less than $2250 per week. For genotype 3, sofosbuvir-ledipasvir-ribavirin would be cost-saving if sofosbuvir cost less than $1500 per week. LIMITATION: Data are lacking on real-world effectiveness of new treatments and some prices. CONCLUSION: From a societal perspective, novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2. PRIMARY FUNDING SOURCE: CVS Health.