Table 1.

Model inputs for an analysis of the cost-effectiveness of HCV therapies in HIV/HCV co-infected patients

Variable	Base Case Value	Range Evaluated in Sensitivity Analyses	Source(s)
Cohort characteristics
Average age, years (S.D.)*	45 (6)	35–55	[44–48]
Proportion male	0.66	0–1.0	[44–47]
Average age at HCV infection (years)*	26 (20–30)	16–36	[52]
Prevalence of IL28B CC genotype	0.32	0.26–0.39	[14]
Mean CD4 count, cells/µl (S.D.)*	520 (100)	350–700	[49–51]
Proportion with CD4 > 500 at baseline on ART	0.756	0.5–1.0	[49–51, 71]
Standardized mortality ratio (SMR)a			[72, 73]
Men	4.69	1.00–6.01
Women	7.80	1.00–14.14
IL28B test characteristics
Sensitivity	0.99	0.95–1.00	[74–76]
Specificity	0.99	0.96–1.00	[74–76]
HCV disease progression
Median years to cirrhosis from age of infection (10%–90%)*	25 (23–27)	10–40	[53]
Median years first liver-event after developing cirrhosis (10%–90%)*	10.8 (9.2–14.3)	5.6–19.3	[25, 77]
Liver-related mortality with cirrhosis (deaths/100 PYs)	2.73	1.38–4.08	[25, 26]
HIV disease progression
Rate of CD4 decline (cells/µl/month)b	3.03–6.38	1.51–9.56	[78]
Incidence of AIDS events (events/100 PYs)c	0.12–0.55	0.06–0.83	[79–86]
HCV therapy efficacy
PEG/RBV therapy
CC genotype at rs12979860
Probability of RVR	0.80	0.74–0.91	[16, 57]
Probability of SVR given RVR	0.91	0.77–0.94	[16, 57]
Probability of withdrawal (toxicity or non-adherence)	0.23	0.19–0.29	[57]
Probability of withdrawal due to toxicity	0.10	0.08–0.13	[87]
Total probability of SVR	0.55	0.40–0.69	[16, 54–57]
Non-CC allele (TT or TC)
Probability of RVR	0.42	0.33–0.52	[16, 57]
Probability of SVR given RVR	0.64	0.57–0.73	[16, 57]
Probability of withdrawal (toxicity or non-adherence)	0.23	0.19–0.29	[57]
Probability of withdrawal due to toxicity	0.10	0.08–0.13	[87]
Total probability of SVR	0.20	0.13–0.30	[16, 54–57]
PEG/RBV/TVR
Probability of having treatment failure (HCV viremia >1,000/ml)	0.18	0.02–0.21	[88]
Probability of withdrawal (toxicity or non-adherence)	0.18	0.06–0.23	[3]
Probability of withdrawal due to toxicity	0.08	0.03–0.10	[88, 89]
Total probability of SVR	0.74	0.65–0.86	[3]
IFN-free therapy
Probability of withdrawal	0.03	0.02–0.04	[6, 7]
Probability of withdrawal for toxicity	0.006	0.004–0.009	See text
Total probability of SVR	0.90	0.80–0.95	[6, 7]
Probability of death due to toxicity for all strategies	0	0–0.029	[57, 88, 90]
HIV therapy efficacy
ART efficacy (proportion HIV RNA < 400 copies/ml at 24 weeks)d	0.15–0.86	0.13–0.99	[91–95]
ART efficacy (proportion HIV RNA < 50 copies/ml at 24 weeks)d	0.15–0.65	0.12–0.75	[91–95]
CD4 rise on suppressive ART (cells/µl/month)d	26–90	13–135	[91–95]
HIV loss to follow-up (rate/100 PYs)e	24.17	12.09–36.26	[96]
Costs
Costs of screening tests and ART
IL28B assay test	$80	$40-$120	[31]
ART costsd	$1,600-$4,800	$800-$7,700	[33, 34, 38]
Healthcare costs
Without HCV (HIV only)f	$300- $20,600	$150-$30,900	[31, 32, 35–37]
With HCVf	$370-$23,300	$190-$35,000	[19, 31, 39]
HCV therapy costs/month
TVR	$15,200	$7,600-$23,000	[33]
PEGg	$2,100	$1,100-$3,200	[33]
RBVh	$1,400	$700-$2,100	[33]
Filgrastimi	$1,900	$900-$2,700	[33]
Clobetasol propionatej	$160	$80-$320	[33]
Total costs of dual therapyl	$43,000	$21,500-$64,500	[31, 33]
Total costs of triple therapyk	$87,300	$43,700-$131,000	[31, 33]
Total costs of IFN-free therapy	$131,000	$98,200-$196,500	See text
Cost of treatment ending toxicity for triple and IFN-free therapy	$360	$180-$540	[30, 31, 33, 97, 98]
Cost of treatment ending toxicity for dual therapy	$420	$210-$630	[30, 31, 33, 57, 97]
Provider visit costsm	$120	$60–180
Quality of life
HCV-related quality of life
No fibrosis to moderate fibrosis	0.89	0.75–0.95	[20, 22, 43]
Cirrhosis	0.62	0.55–0.75	[20, 22, 43]
Decompensated cirrhosis	0.48	0.40–0.60	[20, 22, 43]
On IFN (applied to appropriate HCV-attributable QoL)	0.90	0.84–0.96	[42]
On IFN-free therapy (applied to appropriate HCV-attributable QoL)n	0.95	0.90–0.99	See text
Major toxicity decrement (monthly)o	0.16	0.09–0.25	[99]
HIV-related quality of life (CD4 cells/µl)
>500	0.87	0.78–0.96	[41]
351–500	0.86	0.77–0.95	[41]
251–350	0.86	0.77–0.95	[41]
101–250	0.85	0.76–0.94	[41]
51–100	0.85	0.76–0.94	[41]
≤50	0.83	0.74–0.92	[41]
With acute AIDS-related eventp	0.69–0.78	0.69–0.78	[40]

SD: standard deviation; IL28B: interleukin-28B; ART: anti-retroviral therapy; PYs: person-years; PEG: peginterferon; RBV: ribavirin; TVR: telaprevir; SVR: sustained virologic response; RVR: rapid virologic response; IFN: interferon; OI: opportunistic infection; MSM: men who have sex with men; IDU: injection drug user

Note: all costs are in 2011 U.S. dollars.

^*These parameters are entered into the model as distributions rather than point estimates, allowing for first-order Monte Carlo variance. Numbers in parentheses next to the base case value represent either the standard deviation (if normally distributed) or the tenth and ninetieth percentile values (if non-normally distributed) of the distribution. The ranges provided in the sensitivity analysis column provide the range of central measure (mean or median) that we tested in sensitivity analyses.

^aThe SMR captures elevated non-HIV and non-HCV mortality among those who are HIV/HCV co-infected. It reflects competing risks of death from substance use and other co-morbidities. To determine the SMR for the entire cohort, we first identified risk-group specific SMRs (MSM, IDU, heterosexual risk) by sex, and then took the weighted average of these estimates, using the proportion of each risk-factor among HIV/HCV co-infected patients.

^bDepending on HIV RNA.

^cDepending on CD4, OI history and event type.

^dDepending on ART regimen.

^eBeginning in month 18 (we assumed no HIV-related loss to follow-up during HCV treatment).

^fDepending on age, sex, duration of HIV infection, and CD4 count.

^g13% of patients received a reduced weekly dose of 135 mcg in response to non-treatment ending neutropenia [100].

^hAssumed to be 1,200 mg/day for a 75 kg person; 36% of patients on triple therapy and 17% of patients on dual therapy receive a reduced dose RBV = 600 mg/day in response to non-treatment ending anemia [100].

ⁱ13% of patients developed non-treatment ending neutropenia (absolute neutrophil count < 750/ml) and received filgrastim 300 mcg/two times weekly [100].

^j28% of patients on triple therapy during the first 3 months of therapy receive 150 g per month for treating mild rash [100].

^kIncludes an additional cost of a nursing visit for patients who have adverse events.

^lDepending on treatment month.

^mTreatment visit costs are higher in the first month compared to other months.

ⁿThe multiplier is applied for 3 months instead of 12 months for IFN-free therapy, resulting in 0.5 quality-adjusted life months saved compared to being on PEG/RBV therapy.

^oThis utility “toll” was subtracted from a patient’s health state utility during the month of a major toxicity event.

^pDepending on type of OI event.