Cost-effectiveness of the once-daily efavirenz/emtricitabine/tenofovir tablet compared with the once-daily elvitegravir/cobicistat/emtricitabine/tenofovir tablet as first-line antiretroviral therapy in HIV-infected adults in the US

Figures & data

Figure 1 Model 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 2 Model schematic for adverse events^b 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.

Table 1 Model baseline population of antiretroviral therapy-naïve HIV-1-infected adult patients

Parameter	Estimate		Reference
Baseline patient population	Stribild™	Atripla®	^Citation2
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/mm^3), %
≤200	12	15
201 to ≤350	32	27
351 to ≤500	32	39
>500	23	20

Abbreviations: HIV, human immunodeficiency virus; SD, standard deviation.

Table 2 Model clinical efficacy estimates

Parameter	Estimate (per 12-week cycle)a	Reference
Mortality
All-cause	Age, gender-specific	^Citation3
HIVb	0.9%	^Citation4
AIDSb	3.5%	^Citation4
Acute kidney injury	26.6%	^Citation5
Chronic kidney disease with dialysisc	1.9%	^Citation6
Probability of AIDS, given nonsuppressive regimens	1.8%	^Citation10
CD4 <50 cells/mm^3 (%, among patients with AIDS)d	55.2%	^Citation11
Proportion achieving virologic response, mean (range per 12-week cycle)
First-line
Atripla®	0.81 (0.28–0.72)	^Citation20,Citation21
Stribild™	0.85 (0.76–0.89)	^Citation20,Citation21
Second-line	0.49 (0.41–0.57)	^Citation22,Citation23
Third-line	0.51 (0.49–0.57)	^Citation10,Citation24,Citation25
Change in CD4 count, mean (range per 12-week cycle)
First-line
Atripla	263 (120–367)	^Citation2,Citation7,Citation8,Citation9,Citation21
Stribild	263 (140–426)	^Citation2,Citation7,Citation8,Citation9,Citation21
Second-line	105 (94–109)	^Citation7,Citation8,Citation9,Citation26,Citation27
Third-line	129 (79–147)	^Citation7,Citation8,Citation9,Citation10,Citation24,Citation25

Notes:

a Values are rounded;

b excess mortality in addition to all-cause;

c average annual mortality by race weighted using Stribild population distribution;

d CD4 count ≤200 cells/mm³ among all patients with AIDS.

Abbreviations: AIDS, acquired immune deficiency syndrome; HIV, human immunodeficiency virus.

Table 3 Model adverse eventa,b rates by treatment

Parameter	Estimatea	Reference
CNS symptomsc
Atripla®	1.8%	^Citation2
Stribild™	0.6%	^Citation2
Renal abnormalities
Atripla	0%	^Citation2
Stribild
No AKI	0.22%	^Citation2
AKI	0.14%	^Citation2
CKD with dialysisd	0.03%	Expert opinion
Rashc
First-line
Atripla	1.4%	^Citation2
Stribild	0%	^Citation2
Second-line	0.7%	^Citation22
Third-line	1.8%	^Citation22,Citation25,Citation28
Elevated lipids
First-line
Atripla	1.3%	^Citation29
Stribild	1.0%	^Citation29
Second-line	1.4%	^Citation26,Citation27
Third-line	2.7%	^Citation25,Citation26,Citation30,Citation31
Other eventsc
First-line
Atripla	0.5%	^Citation2
Stribild	0.5%	^Citation2
Second-line	0.4%	^Citation22
Third-line	0.7%	^Citation22,Citation28

Notes:

a Values are reported as probability per 12-week model cycle and are rounded;

b defined as events causing treatment discontinuation except for elevated lipids causing initiation of lipid-lowering therapy, for which treatment continues with an additional cost;

c events occur only during the first cycle of each line of therapy;

d 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.

Table 4 Model costs by treatment, patient monitoring characteristic, and adverse event

Parameter	Costa	Distributionb	Reference
Product acquisition costs
First-line
Atripla®	4,918	Gamma	^Citation1, ^Citation13
Stribild™	6,559
Second-linec	6,977
Third-lined	9,092
Patient monitoring costse
No virologic failuref	914	Gamma	^Citation32
Virologic failure
CD4 ≥50 cells/mm^3,g	1,561
CD4 <50 cells/mm^3,h	1,620
Patient receiving new line of therapyi	113
Cost of treating adverse events
Rash	226	Gamma	^Citation32
Elevated lipids	186		^Citation13, ^Citation32
CNS symptoms	226		^Citation32
Renal abnormalities
No acute kidney injury	914		^Citation32
Acute kidney injury	33,594		^Citation14, ^Citation32
Chronic kidney disease with dialysis	48,665		^Citation15
Other adverse events causing discontinuation	226		^Citation32

Notes:

a All costs are per 12-week cycle and are reported in 2012 US dollars;

b distributions used in probabilistic sensitivity analysis;

c 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;

d third-line treatment defined as 50% receiving darunavir/r + etravirine, 50% receiving maraviroc + raltegravir + optimized background therapy;

e all cost estimates were averages of high and low managed care rates;²⁵

f 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);

g cost included baseline patient monitoring plus a 15-minute physician office visit, one blood draw, and one viral load assessment;

h cost included baseline patient monitoring plus a 25-minute physician office visit, one blood draw, and one viral load assessment;

i cost included a 15-minute physician office visit.

Abbreviations: CNS, central nervous system; NRTIs, nucleoside reverse transcriptase inhibitors.

Table 5 Model utility estimates by CD4 count and adverse event

Parameter	Utility	Distributiona	Reference
CD4 count (cells/mm^3)		Beta
>500	0.946		^Citation16
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		^Citation33
Lipid-lowering therapy	0		Expert opinion
Rash	−0.034		^Citation33
Renal abnormalities			Expert opinion
No acute kidney injury	0		Expert opinion
Acute kidney injuryb	−0.06		^Citation34
Chronic kidney disease with dialysisc	−0.06		^Citation34

Notes:

a Distributions used in probabilistic sensitivity analysis;

b disutility is applied in the cycle in which the acute episode occurs;

c disutility is applied during cycle of initial diagnosis and all subsequent cycles.

Abbreviation: CNS, central nervous system.

Table 6 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:

a 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 3 One-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 4 Probabilistic 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.

SaxPEDeJesusEMillsAGS-US-236-0102 Study TeamCo-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeksLancet201237998352439244822748591

 PubMed Web of Science ®Google Scholar

National Center for Health StatisticsTable 2. Lifetable for males, 2007–2008Atlanta, GACenters for Disease Control and Prevention2012 Available from: ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/NVSR/59_09/Table02.xlsAccessed March 29, 2013

 Google Scholar

Centers for Disease Control and PreventionHIV Surveillance Report, volume 22, 2010 Available from: http://www.cdc.gov/hiv/topics/surveillance/resources/reports/Accessed January 11, 2013

 Google Scholar

WyattCMAronsRRKlotmanPEKlotmanMEAcute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortalityAIDS200620456156516470120

 PubMed Web of Science ®Google Scholar

ChoiAIRodriguezRABacchettiPBertenthalDVolberdingPAO’HareAMThe impact of HIV on chronic kidney disease outcomesKidney Int200772111380138717805235

 PubMed Web of Science ®Google Scholar

GulickRMLalezariJGoodrichJMOTIVATE Study TeamsMaraviroc for previously treated patients with R5 HIV-1 infectionN Engl J Med2008359141429124118832244

 PubMed Web of Science ®Google Scholar

BakerJVPengGRapkinJTerry Beirn Community Programs for Clinical Research on AIDS (CPCRA)CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infectionAIDS200822784184818427202

 PubMed Web of Science ®Google Scholar

Gilead Sciences IncElvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen (EVG/COBI/FTC/TDF, QUAD STR) for treatment of HIV-1 infection in adultsAntiviral Drugs Advisory Committee Meeting Briefing DocumentMay 11, 2012 Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM303397.pdfAccessed June 27, 2013

 Google Scholar

RockstrohJKLennoxJLDejesusESTARTMRK InvestigatorsLong-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRKClin Infect Dis201153880781621921224

 PubMed Web of Science ®Google Scholar

BánhegyiDKatlamaCda CunhaCAWeek 96 efficacy, virology and safety of darunavir/r versus lopinavir/r in treatment-experienced patients in TITANCurr HIV Res201210217118122339125

 PubMed Web of Science ®Google Scholar

JohnsonMGrinsztejnBRodriguezC96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failuresAIDS200620571171816514301

 PubMed Web of Science ®Google Scholar

AndersonDDeMasiRDeLaitschLSurlesTCoateBWeek 96 outcomes of patients with less treatment experience versus more treatment experience receiving etravirine in the DUET trialsCurr HIV Res201210325626122497697

 PubMed Web of Science ®Google Scholar

HodderSJayaweeraDMrusJRyanRWitekJGrace Study GroupEfficacy and safety outcomes among treatment-experienced women and men treated with etravirine in gender, race and clinical experienceAIDS Res Hum Retroviruses201228654455122206504

 PubMed Web of Science ®Google Scholar

ByakwagaHMurrayJMPetoumenosKEvolution of CD4+ T cell count in HIV-1-infected adults receiving antiretroviral therapy with sustained long-term virological suppressionAIDS Res Hum Retroviruses200925675677619500017

 PubMed Web of Science ®Google Scholar

LeMoing VThiébautRChêneGANRS CO8 (APROCO/COPILOTE) Study GroupLong-term evolution of CD4 count in patients with a plasma HIV RNA persistently <500 copies/mL during treatment with antiretroviral drugsHIV Med20078315616317461859

 PubMed Web of Science ®Google Scholar

MooreRDKerulyJCCD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppressionClin Infect Dis200744344144617205456

 PubMed Web of Science ®Google Scholar

ClotetBBellosNMolinaJMPOWER 1 and 2 study groupsEfficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trialsLancet200736995681169117817416261

 PubMed Web of Science ®Google Scholar

JohnsonMGrinsztejnBRodriguezCAtazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failuresAIDS200519768569415821394

 PubMed Web of Science ®Google Scholar

GirardPMCampbellTGrinsztejnBPooled week 96 results of the phase III DUET-1 and DUET-2 trials of etravirine: further analysis of adverse events and laboratory abnormalities of special interestHIV Med201213742743522413938

 PubMed Web of Science ®Google Scholar

Stribild [Prescribing information]Foster City, CAGilead Sciences Inc2012

 Google Scholar

AntoniouTSmithGSuDImmunologic effectiveness of maraviroc- and raltegravir-containing regimens (R+M+) versus raltegravir-based regimens that do not include maraviroc (R+M−)J Int Assoc Physicians AIDS Care (Chic)201211319219722247337

 PubMedGoogle Scholar

SteigbigelRTCooperDAKumarPNBENCHMRK Study TeamsRaltegravir with optimized background therapy for resistant HIV-1 infectionN Engl J Med2008359433935418650512

 PubMed Web of Science ®Google Scholar

Panel on Antiretroviral Guidelines for Adults and AdolescentsGuidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescentsDepartment of Health and Human Services Updated February 12, 2013. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Appendix B, Table 7, and Table 8Accessed March 29, 2013

 Google Scholar

PriceRxWolters Kluwer Health 2012 Available from: https://pricerx.medispan.com/NDCNumber.aspxAccessed September 7, 2012

 Google Scholar

MAG Mutual Healthcare SolutionsPhysicians’ Fee and Coding Guide 2012Atlanta, GAMAG Mutual Healthcare Solutions2011

 Google Scholar

CandrilliSBellTIrishWMorrisEGoldmanSCairoMSA comparison of inpatient length of stay and costs among patients with hematologic malignancies (excluding Hodgkin disease) associated with and without acute renal failureClin Lymphoma Myeloma200881445118501087

 PubMedGoogle Scholar

BergerAEdelsbergJIngleseGWBhattacharyyaSKOsterGCost comparison of peritoneal dialysis versus hemodialysis in end-stage renal diseaseAm J Manag Care200915850951819670954

 PubMed Web of Science ®Google Scholar

SimpsonKNLuoMPChumneyESunEBrunSAshrafTCost-effectiveness of lopinavir/ritonavir versus nelfinavir as the first-line highly active antiretroviral therapy regimen for HIV infectionHIV Clin Trials20045529430415562370

 PubMed Web of Science ®Google Scholar

RoskellNSShearerAGazzardBThe impact of patient, disease, and treatment-related factors on quality of life for HIV patients on HAARTAbstract MOPE0656 presented at the XVI International AIDS ConferenceAugust 13–18, 2006Toronto, Ontario, Canada

 Google Scholar

SullivanPWGhushchyanVPreference-based EQ-5D index scores for chronic conditions in the United StatesMed Decis Making200626441042016855129

 PubMed Web of Science ®Google Scholar