| Literature DB >> 24039438 |
Timothy Juday1, Todd Correll, Ayanna Anene, Michael S Broder, Jesse Ortendahl, Tanya Bentley.
Abstract
BACKGROUND: February 2013 US treatment guidelines recommend the once-daily tablet of efavirenz/emtricitabine/tenofovir (Atripla®) as a preferred regimen and the once-daily tablet of elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild™) as an alternative regimen for first-line treatment of human immunodeficiency virus (HIV). This study assessed the clinical and economic trade-offs involved in using Atripla compared with Stribild as first-line antiretroviral therapy in HIV-infected US adults.Entities:
Keywords: antiretroviral therapy; cost-effectiveness; human immunodeficiency virus
Year: 2013 PMID: 24039438 PMCID: PMC3770712 DOI: 10.2147/CEOR.S47486
Source DB: PubMed Journal: Clinicoecon Outcomes Res ISSN: 1178-6981
Figure 1Model schematic for health states of an antiretroviral therapy-naïve HIV-1-infected adult US population.
Abbreviations: AIDS, acquired immune deficiency syndrome; AKI, acute kidney injury; CKD, chronic kidney disease; HIV, human immunodeficiency virus.
Figure 2Model schematic for adverse eventsb in an antiretroviral therapy-naïve HIV-1-infected adult US population.
Notes: aRash, renal abnormalities, central nervous system symptoms, and other events causing discontinuation of treatment; bpatients who began to receive lipid-lowering therapy (because of elevated lipids) did not discontinue treatment and faced added costs of lipid-lowering therapy.
Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; HIV, human immunodeficiency virus.
Model baseline population of antiretroviral therapy-naïve HIV-1-infected adult patients
| Parameter | Estimate | Reference | |
|---|---|---|---|
| Baseline patient population | Stribild™ | Atripla® | |
| Age, mean (SD), years | 38 (10.4) | 38 (10.6) | |
| Percentage male, % | 88 | 90 | |
| Nonwhite, % | 39 | 36 | |
| Black/African American, % | 30 | 26 | |
| CD4 count (cells/mm3), % | |||
| ≤200 | 12 | 15 | |
| 201 to ≤350 | 32 | 27 | |
| 351 to ≤500 | 32 | 39 | |
| >500 | 23 | 20 | |
Abbreviations: HIV, human immunodeficiency virus; SD, standard deviation.
Model clinical efficacy estimates
| Parameter | Estimate (per 12-week cycle) | Reference |
|---|---|---|
| Mortality | ||
| All-cause | Age, gender-specific | |
| HIV | 0.9% | |
| AIDS | 3.5% | |
| Acute kidney injury | 26.6% | |
| Chronic kidney disease with dialysis | 1.9% | |
| Probability of AIDS, given nonsuppressive regimens | 1.8% | |
| CD4 <50 cells/mm3 (%, among patients with AIDS) | 55.2% | |
| Proportion achieving virologic response, mean (range per 12-week cycle) | ||
| First-line | ||
| Atripla® | 0.81 (0.28–0.72) | |
| Stribild™ | 0.85 (0.76–0.89) | |
| Second-line | 0.49 (0.41–0.57) | |
| Third-line | 0.51 (0.49–0.57) | |
| Change in CD4 count, mean (range per 12-week cycle) | ||
| First-line | ||
| Atripla | 263 (120–367) | |
| Stribild | 263 (140–426) | |
| Second-line | 105 (94–109) | |
| Third-line | 129 (79–147) | |
Notes:
Values are rounded;
excess mortality in addition to all-cause;
average annual mortality by race weighted using Stribild population distribution;
CD4 count ≤200 cells/mm3 among all patients with AIDS.
Abbreviations: AIDS, acquired immune deficiency syndrome; HIV, human immunodeficiency virus.
Model adverse eventa,b rates by treatment
| Parameter | Estimate | Reference |
|---|---|---|
| CNS symptoms | ||
| Atripla® | 1.8% | |
| Stribild™ | 0.6% | |
| Renal abnormalities | ||
| Atripla | 0% | |
| Stribild | ||
| No AKI | 0.22% | |
| AKI | 0.14% | |
| CKD with dialysis | 0.03% | Expert opinion |
| Rash | ||
| First-line | ||
| Atripla | 1.4% | |
| Stribild | 0% | |
| Second-line | 0.7% | |
| Third-line | 1.8% | |
| Elevated lipids | ||
| First-line | ||
| Atripla | 1.3% | |
| Stribild | 1.0% | |
| Second-line | 1.4% | |
| Third-line | 2.7% | |
| Other events | ||
| First-line | ||
| Atripla | 0.5% | |
| Stribild | 0.5% | |
| Second-line | 0.4% | |
| Third-line | 0.7% | |
Notes:
Values are reported as probability per 12-week model cycle and are rounded;
defined as events causing treatment discontinuation except for elevated lipids causing initiation of lipid-lowering therapy, for which treatment continues with an additional cost;
events occur only during the first cycle of each line of therapy;
patients with AKI may progress to CKD with dialysis only during the cycle following the acute AKI event.
Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; CNS, central nervous system.
Model costs by treatment, patient monitoring characteristic, and adverse event
| Parameter | Cost | Distribution | Reference |
|---|---|---|---|
| Product acquisition costs | |||
| First-line | |||
| Atripla® | 4,918 | Gamma | |
| Stribild™ | 6,559 | ||
| Second-line | 6,977 | ||
| Third-line | 9,092 | ||
| Patient monitoring costs | |||
| No virologic failure | 914 | Gamma | |
| Virologic failure | |||
| CD4 ≥50 cells/mm3, | 1,561 | ||
| CD4 <50 cells/mm3, | 1,620 | ||
| Patient receiving new line of therapy | 113 | ||
| Cost of treating adverse events | |||
| Rash | 226 | Gamma | |
| Elevated lipids | 186 | ||
| CNS symptoms | 226 | ||
| Renal abnormalities | |||
| No acute kidney injury | 914 | ||
| Acute kidney injury | 33,594 | ||
| Chronic kidney disease with dialysis | 48,665 | ||
| Other adverse events causing discontinuation | 226 | ||
Notes:
All costs are per 12-week cycle and are reported in 2012 US dollars;
distributions used in probabilistic sensitivity analysis;
second-line treatment defined as 50% receiving atazanavir with boosted ritonavir (atazanavir/r) and two NRTIs, 50% receiving darunavir with boosted ritonavir (darunavir/r) and two NRTIs;
third-line treatment defined as 50% receiving darunavir/r + etravirine, 50% receiving maraviroc + raltegravir + optimized background therapy;
all cost estimates were averages of high and low managed care rates;25
cost included baseline monitoring components, consisting of a 10-minute physician office visit, one blood draw, one chemistry panel, one complete blood count, one CD4 count, and one viral load assessment (ultrasensitive quantification);
cost included baseline patient monitoring plus a 15-minute physician office visit, one blood draw, and one viral load assessment;
cost included baseline patient monitoring plus a 25-minute physician office visit, one blood draw, and one viral load assessment;
cost included a 15-minute physician office visit.
Abbreviations: CNS, central nervous system; NRTIs, nucleoside reverse transcriptase inhibitors.
Model utility estimates by CD4 count and adverse event
| Parameter | Utility | Distribution | Reference |
|---|---|---|---|
| CD4 count (cells/mm3) | Beta | ||
| >500 | 0.946 | ||
| 351 to ≤500 | 0.933 | ||
| 201 to ≤350 | 0.931 | ||
| 50 to ≤200 | 0.853 | ||
| <50 | 0.781 | ||
| Adverse events (disutilities) | |||
| CNS symptoms | −0.043 | ||
| Lipid-lowering therapy | 0 | Expert opinion | |
| Rash | −0.034 | ||
| Renal abnormalities | Expert opinion | ||
| No acute kidney injury | 0 | Expert opinion | |
| Acute kidney injury | −0.06 | ||
| Chronic kidney disease with dialysis | −0.06 | ||
Notes:
Distributions used in probabilistic sensitivity analysis;
disutility is applied in the cycle in which the acute episode occurs;
disutility is applied during cycle of initial diagnosis and all subsequent cycles.
Abbreviation: CNS, central nervous system.
Summary results for Atripla versus Stribilda
| Cost
| Survival (years)
| QALY
| ICER (LY) | ICER (QALY) | ||||
|---|---|---|---|---|---|---|---|---|
| Lifetime | Δ | Lifetime | Δ | Lifetime | Δ | |||
| Atripla™ | $726,728 | 16.8436 | 14.9565 | |||||
| Stribild® | $733,615 | $6,886 | 16.8625 | 0.0188 | 14.9979 | 0.0414 | $365,750 | $166,287 |
Notes:
Incorporating 3% annual discount rate for cost, LY, and QALY outcomes. All costs are reported in 2012 US dollars. All values are per person and rounded.
Abbreviations: ICER, incremental cost-effectiveness ratio; LY, life year; QALY, quality-adjusted life year.
Figure 3One-way sensitivity analyses.a,b
Notes: aIncorporating 3% annual discount rate for cost, LY, and QALY outcomes. Results expressed in $/QALY for Stribild™ compared with Atripla®; ball parameters were varied by ±10%; cStribild™ had higher costs and lower QALYs than Atripla®.
Abbreviations: AE, adverse event; AIDS, acquired immune deficiency syndrome; AKI, acute kidney injury; CKD, chronic kidney disease; LY, life year; QALY, quality-adjusted life year.
Figure 4Probabilistic sensitivity analyses.a
Notes: aIncorporating 3% annual discount rate for cost, LY, and QALY outcomes. Results expressed in $/QALY for Stribild™ compared with Atripla®. Blue dots represent ICERs when all parameters were varied simultaneously for 5,000 model simulations. Larger red box represents base case. Blue dotted line represents 95% confidence ellipse.
Abbreviations: IC, incremental cost; ICER, incremental cost-effectiveness ratio; IE, incremental effectiveness; QALY, quality-adjusted life year.