Cost–Effectiveness of CYP2B6 Genotyping to Optimize Efavirenz Dosing in HIV Clinical Practice

Figures & data

Figure 1. Schema for evaluation of CYP2B6 genotyping before initiation of efavirenz-based initial HIV therapy.

All antiretroviral therapy regimens also include emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg).

Conclusive: Genotype result can be interpreted in order to assign a dosing strategy; EFV: Efavirenz; Inconclusive: Genotype result cannot be interpreted (e.g., genotyping fails on the sample).

Figure 2. Clinical and economic outcomes of standard care, CYP2B6 genotyping for efavirenz dosing, and universal lower dose.

The solid line shows the decrease in total discounted lifetime cost (horizontal axis) with the universal lower dose strategy (triangle) and the genotyping strategy (rectangle) compared with the standard care strategy (circle), assuming equal efficacy among strategies. The difference in quality-adjusted life expectancy among strategies (vertical axis) is minimal. When the efficacy of the lower dose is assumed to be lower compared with 600 mg, the dashed (6% lower) and dotted (11% lower) lines show the lower lifetime cost and quality-adjusted life expectancies for the universal lower dose and genotyping strategies. The cost–effectiveness ratios for these strategies are represented by the slopes of the lines.

Table 1. Selected model inputs for an analysis of genotyping to inform efavirenz dosing in HIV.

Variable	Base case	Range	Ref.
Cohort characteristics at ART initiation:
– CD4 count, mean cells/μl (SD)	317 (283)	135–517	[39]
– Age (years)	43	34–50	[39]
– Male (%)	84		[39]
– HIV RNA distribution post-acute infection (%):			Derived from [3]
• >100,000 copies/ml	25.1
• 30,001–100,000 copies/ml	42.0
• 10,001–30,000 copies/ml	20.9
• 3001–10,000 copies/ml	5.6
• <3000 copies/ml	6.4
Baseline ART adherence:
– Adherence <50%	3.1		[35,40]
– 50% ≤adherence <95%	50.7
– Adherence ≥95%	46.2
First-line ART efficacy:
– HIV RNA suppressed at 6 months, overall (%)	91	See Table 2	[37]
– Adherence <5%; >95%	0; 96		Derived from [41]
– Virologic failure rate after 6 months, per 100 PY
– Adherence <65%; >95%	93.3; 1.6		Derived from [41]
– Loss to follow-up^† rate on ART, per 100 PY	7.5		[42]
– Adherence <50%; >95%	84.5; 0.1		Derived from [41]
– Return to care rate, per 100 PY	16.9		[42]
First-line ART monthly cost (US$)^‡:			[38]
– Branded EFV 600mg/FTC/TDF	1,850
– Branded EFV 400mg/FTC/TDF	1,630
– Branded EFV200mg/FTC/TDF	1,410
– Generic EFV 600mg with branded FTC/TDF	1,400
– Generic EFV 400mg with branded FTC/TDF	1,330
– Generic EFV 200mg with branded FTC/TDF	1,260
– Substitute 1st-line ART regimen^§	2,190
Subsequent ART regimen monthly costs (US$)	2520 -3570		[38]
Genotyping test cost (US$)	349	10–500^¶	Assumption based on [43]
Efavirenz treatment-limiting adverse event:
– Duration (days)	30	30–100^¶	[44]
– Evaluation cost for clinical visits and lab test (US$)	202	100^¶-400^¶	Calculated from [45]
– Quality of life multiplier	0.9	0.8–1.0	Assumption
– Discontinue care after experiencing adverse event (% of those experiencing event, time to return to care)	0	50–100% for 6–24 months	Assumption

^†Loss to follow-up is defined as an interruption in care of at least 12 months.

^‡Branded costs are 77% of average wholesale price reflecting discounts to institutional purchasers, and generic costs are 25% of average wholesale price.

^§Weighted average cost of substitute options, including integrase inhibitor-based regimens (75%), nonnucleoside reverse transcriptase inhibitor-based regimens (15%), and protease inhibitor-based regimens (10%).

^¶Sensitivity analysis based on assumption.

ART: Antiretroviral therapy; EFV: Efavirenz; FTC: Emtricitabine (200 mg); PY: Person-years; SD: Standard deviation; TDF: Tenofovir disoproxil fumarate (300 mg).

Table 2. Efficacy and toxicity of efavirenz-based regimen.

Variable	Base case (%)	Range (%)	Ref.
Patients without risk genotype
Proportion of all patients	39.7	39.7–90.0^†	Derived from [7,39]
Efficacy: EFV(600 mg) FTC/TDF regimen	91		[37]
Efficacy: EFV(400 mg) FTC/TDF regimen	91		[37]
Toxicity: EFV(600 mg) FTC/TDF regimen	3		Assumption based on [3,48]
– Toxicity: EFV(400 mg) FTC/TDF regimen	2	0–4
Patients with risk genotype requiring EFV 400 mg
Proportion of all patients	47.1	47.1–8.0^†	Derived from [7,39]
Efficacy: EFV(600 mg) FTC/TDF regimen	91		[37]
Efficacy: EFV(400 mg) FTC/TDF regimen	91	75^†-91	[37]
Toxicity: EFV(600 mg) FTC/TDF regimen	6	3–9	Assumption based on [3,48]
Toxicity: EFV(400 mg) FTC/TDF regimen	3
Patients with risk genotype requiring EFV 200 mg
– Proportion of all patients	13.2	13.2–2.0^†	Derived from [7,39]
Efficacy: EFV(600 mg) FTC/TDF regimen	91		[37]
Efficacy: EFV(400 mg) FTC/TDF regimen	91	75^†–91	[37]
Toxicity: EFV(600 mg) FTC/TDF regimen	9	6–12	Assumption based on [3,48]
Toxicity: EFV(400 mg) FTC/TDF regimen	6	3–9

^†Sensitivity analysis based on assumption.

EFV: Efavirenz; FTC: Emtricitabine (200 Mg); TDF, Tenofovir disoproxil fumarate (300 mg).

Table 3. Results of an analysis of CYP2B6 genotyping before initiation of efavirenz-based initial HIV therapy comparing standard care (without genotyping) to genotyping: incremental cost–effectiveness ratios of genotyping (US$/QALY).

Strategy	Total lifetime QALYs	Incremental QALYs	No generic efavirenz availability			Generic efavirenz availability
			Total lifetime cost (US$)	Incremental cost (US$)	$/QALY	Total lifetime cost (US$)	Incremental cost (US$)	$/QALY
Efavirenz lower dose efficacy equal to full dose (91% suppressed at 24 weeks)
Genotyping	13.4688		386,000			349,000
Standard care	13.4686	(0.0002)	404,500	18,500	Dominated	356,600	7600	Dominated
Efavirenz lower dose efficacy less than full dose (85% suppressed at 24 weeks)
Genotyping	13.4474		388,600			355,300
Standard care	13.4686	0.0212	404,500	15,900	747,500	356,600	1300	60,700
Efavirenz lower dose efficacy less than full dose (80% suppressed at 24 weeks)
Genotyping	13.4316		391,800			356,700
Standard care	13.4686	0.0370	404,500	12,700	342,800	356,600	(200)^†	Cost-saving
Efavirenz lower dose efficacy less than full dose (75% suppressed at 24 weeks)
Genotyping	13.4210		394,900			360,400
Standard care	13.4686	0.0476	404,500	9600	201,700	356,600	(3800)	Cost-saving

^†Due to rounding, this number does not reflect the difference between total lifetime costs as shown in the table.

Dominated: strategy is more expensive and less effective than another strategy; QALY: Quality-adjusted life year.

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