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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Ann Intern Med. Author manuscript; available in PMC 2013 July 15.
Published in final edited form as:
PMCID: PMC3664029

Economic savings versus health losses: The cost-effectiveness of generic antiretroviral therapy in the United States



US HIV treatment guidelines recommend branded once-daily, one-pill efavirenz/emtricitabine/tenofovir as preferred first-line antiretroviral treatment (ART). With the anticipated approval of generic efavirenz in 2012 in the US, the cost of a once-daily, three-pill alternative (generic efavirenz, generic lamivudine, tenofovir) will decrease, but adherence and virologic suppression may be reduced.


To assess the clinical impact, costs, and cost-effectiveness of the generic-based three-pill regimen compared to the branded, co-formulated regimen. To project the potential national savings in the first year of a switch to generic-based ART.


Mathematical simulation of HIV disease.

Data Sources

Published data from US clinical trials and observational cohorts.

Target Population

HIV-infected patients eligible to start on or switch to an efavirenz-based generic ART regimen.

Time Horizon

Lifetime, One-year


US health system


No ART (for comparison), Three-pill Generic ART, and Branded ART

Outcome Measures

Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICER, $/quality-adjusted life expectancy [QALY]).

Results of Base-Case Analysis

Compared to No ART, Generic ART has an ICER of $21,100/QALY. Compared to Generic ART, Branded ART increases lifetime costs by $42,500, and per-person survival gains by 0.37 QALYs, for an ICER of $114,800/QALY. Estimated first-year savings, if all eligible US patients start on or switch to Generic ART, are $920 million.

Results of Sensitivity Analysis

Most plausible assumptions about Generic ART efficacy and costs lead to Branded ART ICERs >$100,000/QALY.


The efficacy and price reduction associated with generics are unknown; estimates are intended to be conservative.


Compared to a slightly less effective generic-based regimen, the cost-effectiveness of first-line Branded ART exceeds $100,000/QALY. Generic-based ART in the US could yield substantial budgetary savings to HIV programs.


For the first time since the 1996 US Food and Drug Administration (FDA) approval of combination antiretroviral therapy (ART), there is now potential for a potent, largely generic, first-line regimen. In January 2012, generic versions of lamivudine became available in the US, and later in 2012, generic versions of efavirenz are expected. The once-daily, three-pill regimen of generic efavirenz, generic lamivudine, and branded tenofovir could substantially reduce costs of first-line ART.

Even if the potency, tolerability, and safety of generic lamivudine and efavirenz meet the required FDA standards of their proprietary equivalents, there remain two potential disadvantages. The first is increased pill burden; the currently recommended branded tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) is co-formulated as a single, once-daily pill. If pill burden hinders adherence, thereby reducing viral suppression, a three-pill generic alternative may lead to worse outcomes (1, 2). Second, substituting lamivudine for emtricitabine may reduce potency and increase the frequency of M184V mutations upon first-line failure, thereby compromising the effectiveness of subsequent regimens (3, 4). A once-daily two-pill option (tenovir/emtricitabine, efavirenz) offers a potential intermediate alternative, with some cost savings (by using generic efavirenz), lower pill burden, and avoidance of lamivudine. Given these trade-offs, we sought to assess the clinical impact, cost, and cost-effectiveness of the generic-based ART compared to branded co-formulated alternatives.


Analytic Overview

We evaluate three strategies for HIV-infected persons eligible to initiate an efavirenz-based regimen: 1) No ART (for comparison); 2) Three-pill Generic ART, consisting of efavirenz (generic), lamivudine (generic), and tenofovir (patented Viread®, Gilead Sciences); or 3) Branded ART, consisting of the one-pill co-formulated efavirenz/emtricitabine/tenofovir (Atripla®, Gilead/Bristol-Myers Squibb). For ease of identification, we refer to the “Generic ART strategy”, even though it contains one branded component. In the base case, Generic ART differs from Branded ART in three ways. First-line viral suppression efficacy is lower owing to both increased pill burden (poorer adherence) and decreased potency (substitution of lamivudine for emtricitabine). Second, viral suppression efficacy in second-line therapy is lower due to reported increased frequency of M184V mutations associated with failure of first-line viral suppression on lamivudine (vs. emtricitabine). Finally, first-line drug costs are lower. We vary all of these parameters in sensitivity analyses.

We use the Cost-effectiveness of Preventing AIDS Complications (CEPAC) US Model – a previously published mathematical simulation of HIV (59) – to project clinical outcomes (quality-adjusted life years [QALYs]) and economic outcomes (per-person lifetime costs) for the three strategies. These projections are then used to evaluate incremental cost-effectiveness ratios, which we report from a US health system perspective, discounted at 3%/annum (10). We also project the undiscounted savings in the first year among all patients who are on or starting on an efavirenz-based treatment and eligible to switch from Branded to Generic ART.

The CEPAC-US Model

CEPAC-US characterizes HIV disease progression as a sequence of monthly transitions between “health states.” These health states summarize current status, relevant history, quality of life, and resource use; they also determine the risk of future clinical events. Health states are stratified by CD4 count (5 strata), HIV RNA level (6 strata), ART regimen, and disease acuity (e.g. treatment-related toxicity or opportunistic infection [OI]). In the model, the level of HIV RNA determines the rate of CD4 decline, and the CD4 count determines the frequency of OIs and AIDS-related death. Patients face a risk HIV-related mortality (OIs and otherwise), or age- and sex-adjusted background mortality (11, 12).

We capitalize on the model's capacity to consider early-regimen mutations and virologic failure in determining the efficacy of subsequent regimens. Per current US guidelines (13), we assume all newly-presenting patients initiate therapy immediately. Effective ART functions to suppress HIV RNA and increase CD4 count at rates reported (1421). Quarterly clinic visits, CD4 and HIV RNA monitoring confirm the possibility of “early suppression” followed by “late failure,” two model-based parameters that define ART efficacy. Early suppression of a regimen is the fraction of patients virologically suppressed after 24 weeks. Suppressed patients subsequently have a probability of late failure, defined as a monthly probability of virologic rebound after initial suppression.

Once detected, virologic failure results in a switch to a subsequent regimen and another -- albeit diminishing -- opportunity for suppression. The model translates input variation in adherence and regimen selection into changes in ART efficacy, and thereby changes in clinical and cost outcomes.

Input Parameters


The entering cohort is modeled as similar to those newly diagnosed HIV-infected patients in the US in 2009 (22), among whom 84% were male. Recent US data suggest a mean CD4 count at presentation of 317/μl (Table 1) (22, 23).

Table 1
Base case inputs for a model of Generics vs. Branded ART in the US

ART Efficacy

In the No ART strategy, patients follow the natural history of HIV disease without access to ART. Branded ART results in 24-week virologic suppression of 85% – from a clinical trial using co-formulated, one-pill tenofovir/emtracitabine/efavirenz -- with a 0.21% monthly probably of late failure after 24 weeks (14). For this strategy, we use a second-line, protease-inhibitor-based regimen with a 24-week suppression efficacy of 73% (17, 18). Three-pill Generic ART leads to 24-week virologic suppression of 78%, from a clinical trial of efavirenz, lamivudine, and tenofovir (15). Using trial data, we derive the monthly probability of failure after 24 weeks as 0.45%, substantially higher than that of Branded ART. We also decrease the suppression rate of second-line ART by 5%, from 73% with Branded to 68% with Generic ART, an assumption that captures the increased risk of M184V mutations resulting from first-line lamivudine use (3, 4). Efficacies for subsequent ART regimens (Appendix Table 1) are otherwise identical between treatment strategies.

An intermediate option to Three-pill Generic ART is a two-pill alternative, using co-formulated tenofovir/emtricitabine (Truvada®, Gilead Sciences) and generic efavirenz. Recognizing the uncertainty surrounding the comparative efficacy of once-daily one-versus two- versus three-pill regimens, we examine all options together in generalized sensitivity analyses designed to illuminate the trade-offs among early efficacy, late failure, and costs. We begin with a Two-pill Generic ART 24-week suppressive efficacy of 84% and a monthly probability of failure thereafter of 0.43% (19); we maintain the full potency of the second-line regimen because of the inclusion of emtricitabine in the first-line regimen (Table 1). Other efficacy/cost combinations are also examined.


The annual cost for Branded ART is $15,300 (25), 77% of the published average wholesale price (AWP) for standard dosing (Table 1) (26). We assume a 75% price reduction from AWP for the generic components of the Three-pill Generic ART regimen ($9,200/year) and the Two-pill Generic ART regimen ($11,600/year) and explore reductions from 35% to 95%. Subsequent ART regimen, laboratory monitoring, and routine care costs are in Appendix Table 1. All costs are in 2009 USD.

Sensitivity Analyses

We use one-way and multi-way sensitivity analyses to understand the impact of uncertainty in early virologic suppression efficacies, probabilities of late failure, and the comparative cost-savings from Generic ART. We also examine alternative second-line ART efficacies associated with an increased presence of M184V mutations, and consider a cohort with higher/lower CD4 counts leading to varying durations on ART. Finally, we examine the impact of our results with risk-group adjustments to our estimates of non-HIV-related mortality.

Potential Savings in the First Year

To determine the potential savings in the US during the first year, we multiply the number of persons eligible to start or switch to Generic ART by the per-person savings. “Incident cases” likely to be prescribed efavirenz are calculated as the product of: the anticipated new diagnoses in the US per year (8,294 in 2009) (22); the estimated fraction of HIV-infected people on ART (36%) (27); and the likelihood that an efavirenz-based regimen is selected as first-line (85%) (28). “Prevalent cases” switching from an efavirenz-based branded regimen to its generic-based alternative are calculated as the product of: CDC-based projections of the number of persons living with HIV in the US (1,200,000) (22); the estimated proportion on ART (36%) (27); and the estimated proportion of those on ART who receive an efavirenz-based regimen (34%, Gebo K, Personal communication) (27). We multiply the number of persons eligible for a generic start or switch by the potential per-person savings associated with Generic ART in the first year. These savings are the difference between the undiscounted annual costs of Branded ($15,300) and Generic ($9,200) ART, or $6,100 per person.


Base Case Results

In the base case, the discounted per-person quality-adjusted life expectancies from age 43 are 4.05 QALYs (undiscounted 4.58) for No ART, 12.08 QALYs (undiscounted 18.36) for Three-pill Generic ART, and 12.45 QALYs (undiscounted 19.32) for Branded ART (Table 2). Per-person discounted lifetime costs increase from $131,200 (No ART) to $300,300 for Generic ART to $342,800 for Branded ART. Compared to No ART, Three-pill Generic ART results in an ICER of $21,100/QALY. The ICER for Branded ART, compared to Generic ART, is $114,800/QALY (Table 2, Figure 1a).

Figure 1Figure 1
The clinical and economic outcomes of Branded and Generic ART. Per-person lifetime costs are on the horizontal axis and quality-adjusted life expectancy on the vertical axis. Gray solid lines indicate the anticipated incremental cost-effectiveness ratios ...
Table 2
Clinical outcomes, cost, and cost-effectiveness of Generic vs. Branded ART in the US

Two-pill Generic ART

Two-pill Generic ART results in greater survival than Three-pill Generic in the base case (12.25 vs. 12.08 QALYs). When Three- and Two-pill Generic ART, and Branded ART are compared incrementally, ICERs are $21,100/QALY for Three-pill Generic ART vs. No ART, $95,400/QALY for Two-pill Generic vs. Three-pill Generic ART, and $130,600/QALY for Branded vs. Two-Pill Generic ART (Table 2, bottom, Figure 1b).

Sensitivity Analyses

Three-pill Generic ART

The ICER for Branded ART compared to Three-pill Generic ART is sensitive to the comparative cost and efficacy of Generic ART (Figure 2a). At the base case Generic ART efficacy (78% 24-week suppression, 0.45%/month probability of late failure), Branded ART has an ICER>$100,000/QALY, provided that the discount from AWP for Generic ART is greater than 65% ([filled circle in circle], Figure 2a). If the probability of 24-week suppression remains lower for Three-pill Generic compared to Branded ART, but the monthly probability of late failure is the same for both 0.21%), then the ICERs of Branded compared to Three-pill Generic ART are substantially higher at every combination of Generic ART 24-week efficacy and price reduction (Figure 2b). Under such conditions, even modest price reductions (>40% AWP) for the generic regimen components result in ICERs for Branded ART compared to Generic ART >$100,000/QALY ([filled circle in circle], Figure 2b).

Figure 2Figure 2
Two-way sensitivity analyses demonstrating the changes in the incremental cost-effectiveness ratio (ICER) of Branded ART, compared to the Three-pill Generic ART (vertical axis), as a function of the generic drug price reduction (horizontal axis) and the ...

Two-pill Generic ART

Results for Two-pill Generic ART are similarly sensitive to regimen efficacy – most importantly to the probability of late failure – as well as to costs. When Two-pill Generic, Three-pill Generic, and Branded ART all have the same probability of late failure (0.21% at 24 weeks), then Two-pill Generic ART has an ICER <$100,000/QALY compared to Three-pill Generic ART at price reductions of 50% AWP ($62,600/QALY Table 3, top). If Branded and Two-pill Generic ART have similar probabilities of late failure (0.21%) -- lower than that of the Three-pill Generic ART (0.45%) -- then Two-pill Generic ART becomes much more attractive. At all price reductions examined, Two-pill Generic ART becomes the best choice, because it dominates (more effective and less costly) Three-pill Generic ART and because of the very high ICERs for Branded ART ($101,300–2,540,100/QALY, Table 3, middle).

Table 3
Three-way sensitivity analysis on Two-pill vs. Three-pill Generic ART, probability of late failure after 24 weeks, and price reduction.

Other Sensitivity Analyses

In other sensitivity analyses we observe variability in outcomes, but no material impact on the qualitative cost-effectiveness findings when we change the efficacy of second-line ART (to capture changes related to potential lamivudine-related resistance, Branded ART ICERs $109,300–120,600/QALY); when we consider a healthier presenting cohort (mean CD4 count = 650/μl, Branded ART ICER $143,200/QALY); or when we adjusted background mortality rates by risk group (Branded ART ICER $117,400/QALY, (Appendix Tables 25).

Potential Savings in the First Year

The per-person undiscounted savings for Three-pill and Two-pill Generic ART compared to Branded ART are $6,100/year and $3,700/year. We estimate that there are 2,500 persons newly-diagnosed and initiating ART (“incident cases”) and 147,300 HIV-infected persons (“prevalent cases”) currently taking an efavirenz-based regimen who could switch to Generic ART in the US (27). Combining the benefits from both incident and prevalent cases, the potential estimated savings in the first year associated with use of Three-pill Generic ART in the base case are $920 million; the anticipated savings are substantially less for Two-pill Generic ART ($560 million). Anticipated savings in the first year from Three-pill Generic ART range from $200 million to $1.29 billion at price reductions from AWP from 35 to 95% (Appendix Figure 1).


We project that a population-wide switch from first-line Branded to Generic ART in the US will result in lifetime average savings of $42,500 per eligible patient with only a modest survival loss of 0.37 QALYs. Viewed on a population-wide basis, the aggregate savings in the first year alone would amount to nearly $1 billion. Accounting for potential decrements in the short- and long-term efficacy of generic-based regimens, we find that the incremental cost-effectiveness of a first-line branded regimen becomes unattractive by a standard (>$100,000/QALY) recently used in the US (2931).

The market for antiretrovirals in the US – largely financed with governmental support – was estimated at nearly $9 billion in 2011 (32). Much is at stake as major components of effective HIV therapy become generically available this year. The significance of this analysis lies not only in its relevance to the current discussion of generic efavirenz, but also in the development of a framework by which future generations of generic antiretrovirals – and the trade-off between drug efficacy and costs savings – may be evaluated.

Generics will save money but may reduce health benefits, a trade-off that may be emotionally unattractive. Fewer than 2% of published cost-effectiveness analyses report on this combination of both lower health benefits but also lower costs (33). Some may reject such interventions as substandard, and therefore eliminate their consideration on ethical grounds. However, economic evaluation of “decremental cost-effectiveness” can identify opportunities to improve efficiency in health care delivery by reallocating resources to higher-value, lifesaving alternatives. This is particularly true as an increasing number of proven effective, yet costly interventions further stretch the resources of the US health care system. For example, fewer than half the state AIDS Drug Assistance Programs (ADAPs) in the US include protease-inhibitor-based Hepatitis C virus (HCV) regimens ($90,100/treatment course) in their formularies, despite these drugs having ICERs <$100,000/QALY (as reported in mono-infected patients)33,34.(34, 35) For every fifteen people switched to a generic-based HIV regimen (potential annual savings ~$6,100/person), one person with HIV/HCV co-infection could be treated for – and potentially cured of – chronic hepatitis C (34). With 300,000 people in the US eligible for these new HCV therapies, this would represent a major treatment opportunity (35). President Obama's 2010 National HIV/AIDS Strategy (NHAS) (36) is explicitly financed by “re-purposed” rather than new funds (37). In an era where dedication to the national HIV mission requires “re-directed” financing, the potential $1 billion savings from generic-based regimens might be an efficient source available for national reinvestment (38).

Our assumptions with regard to generic drug efficacy and pricing are conservative. Despite the absence of clinical trial evidence suggesting any differential, we assumed that daily lamivudine would be less effective and promote more resistance, compared to emtricitabine, when used as either a first- or second-line regimen. We also assumed an adherence advantage for a daily single-pill regimen, despite mixed data on how pill burden affects virologic suppression (1, 39). Our 75% price reduction is justified by evidence that generic prices fall by as much as 80–85% of published branded prices when five or more manufacturers enter a market 39,40.(40, 41) More than seven suppliers currently provide FDA-approved generic efavirenz outside the US, under PEPFAR auspices (42).

We note several limitations in this analysis. First, the $100,000/QALY threshold for cost-effectiveness, while frequently cited, may be debated (30, 43, 44). Higher willingness-to-pay thresholds could result in branded regimens falling within an acceptable range. While we conduct this analysis from the US health system perspective, we acknowledge that the savings realized from a policy switch to generic-based regimens will accrue differently from one payer to the next (e.g. state ADAPs vs. state Medicaid programs vs. the US Veterans Administration); these savings may not be reinvested in HIV care, or even in health care. The savings may also be greater than we project. If efforts to improve HIV case identification, linkage to and retention in care are successful-- thus increasing the outlay for HIV medications -- the anticipated savings from generics could exceed our $920 million estimate (45).

Compared to a slightly less effective regimen containing generics, we find that the incremental cost-effectiveness for the branded one-pill first-line ART regimen exceeds $100,000/QALY. Starting or switching to generic-based regimens would initially yield annual savings approaching $1 billion for programs that fund HIV treatment in the United States.


The authors thank Kelly Gebo, MD, MPH and the HIV Research Network for helpful data.

INSTITUTIONAL REVIEW BOARD APPROVAL: This study was exempt from the Institutional Review Board by the Partners Human Research Committee Protocol # 200P001927.

Role of the Funding Source This work was supported by the National Institutes of Allergy and Infectious Disease (R37 AI42006 and R01 AI093269). The funding source did not have any role in the study's design, conduct, reporting, and decision to submit the manuscript.


Appendix Table 1

Base case ART efficacy inputs and costs for later ART regimens in an analysis for first-line Generics vs. Branded ART in the US

VariableBase case valueRangeReference
Efficacy of ART (% patients with HIV RNA suppression at 24 weeks, CD4 increase at 48 weeks,
monthly probability of late failure after 24-weeks)
All regimen efficacy of 3rd-6th line
 Third-line61%; 121 cells/μl, 1.71%(17, 18)
 Fourth-line65%; 102 cells/μl, 1.71%(16)
 Fifth-line40%; 119 cells/μl. 2.19%(20, 21)
 Sixth-line15%; 45 cells/μl, 2.19%(20)
Costs (2009 USD)
Antiretroviral therapy, annual(25)
CD4 test, annual820(46)
HIV RNA test, annual1,500(46)
Routine care by CD4 count, annual(4749)

Appendix Table 2

Sensitivity analysis on the 2nd-line ART efficacy for the Three-pill Generic ART

2009 USD
life expectancy
2nd Line ART Efficacy = 73%
No ART131,2004.05
Three-pill Generic ART301,30012.1121,100
Branded ART342,80012.45120,600
2nd Line ART Efficacy = 72%
No ART131,2004.05
Three-pill Generic ART300,80012.0921,100
Branded ART342,80012.45117,300
2nd Line ART Efficacy = 67%
No ART131,2004.05
Three-pill Generic ART299,80012.0721,000
Branded ART342,80012.45112,400
2nd Line ART Efficacy = 63%
No ART131,2004.05
Three-pill Generic ART299,30012.0521,000
Branded ART342,80012.45109,300

ART: Antiretroviral therapy; USD: United States dollar; QALY: Quality-adjusted life year

Appendix Table 3

Sensitivity analysis demonstrating the impact on clinical outcomes, cost, and cost-effectiveness for alternative mean CD4 cell counts of the presenting cohort

2009 USD
life expectancy
Mean CD4 = 350/μl
No ART131,3004.30
Three-pill Generic ART303,80012.3721,400
Branded ART346,90012.73118,500
Mean CD4 = 400/μl
No ART131,4004.70
Three-pill Generic ART308,60012.7722,000
Branded ART352,80013.13121,700
Mean CD4 = 450/μl
No ART131,3005.11
Three-pill Generic ART312,90013.1322,600
Branded ART358,00013.49125,200
Mean CD4 = 500/μl
No ART131,0005.51
Three-pill Generic ART316,50013.4423,400
Branded ART362,70013.80128,200
Mean CD4 = 550/μl
No ART130,7005.92
Three-pill Generic ART319,70013.7124,300
Branded ART366,40014.06133,700
Mean CD4 = 600/μl
No ART130,2006.33
Three-pill Generic ART322,20013.9325,300
Branded ART369,40014.27139,800
Mean CD4 = 650/μl
No ART129,6006.73
Three-pill Generic ART324,20014.1226,400
Branded ART371,90014.45143,200

ART: Antiretroviral therapy

Appendix Table 4

Sensitivity analysis demonstrating the impact on clinical outcomes, cost, and cost-effectiveness when background mortality is adjusted by risk-group*

2009 USD
life expectancy
No ART130,7004.02 (4.54)
Three-pill Generic ART294,70011.79 (17.78)21,100
Branded ART336,20012.14 (18.69)117,400
No ART130,7004.02 (4.54)
Three-pill Generic ART294,70011.79 (17.78)21,100
Two-pill Generic ART310,30011.95 (18.13)95,000
Branded ART336,20012.14 (18.69)136,900

USD: United States Dollar; QALY: quality-adjusted life year; ART: antiretroviral therapy

*Risk-group adjustments account for differences in non-HIV-related (background) mortality between those at highest risk for HIV and the general population. We considered five sex/risk-groups in our adjustment: men who have sex with men, male and female injection drug users, and male and female high-risk heterosexuals. For each of these groups, we applied a published risk-group specific standardized mortality ratio (SMR) to age- and sex-adjusted non-HIV related mortality rates.(50) We then weighted these risk-group-specific mortality rates according to the distribution of risk-groups among HIV-infected individuals in the US,(51) as well as to the predicted changes in the distribution over time to get age-, sex-, and risk-adjusted non-HIV mortality rates.

Appendix Table 5

Three-way sensitivity analysis on Two-pill vs. Three-pill Generic ART, probability of virologic failure after 24 weeks and price reduction when background mortality is adjusted by risk group*

2009 USD
life expectancy
Probability of late virologic failure (Branded=0.21%, Two-pill Generic=0.21%, Three-
pill Generic=0.21%)
25% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART334,60011.97dominated
Two-pill Generic ART334,80012.1325,200
Branded ART336,20012.14124,700
50% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART307,80011.9722,300
Two-pill Generic ART317,80012.1363,100
Branded ART336,20012.141,680,400
75% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART281,00011.9718,900
Two-pill Generic ART300,60012.13122,700
Branded ART336,20012.143,391,200
Probability of late virologic failure (Branded=0.21%, Two-pill Generic=0.21%, Three-
pill Generic=0.45%)
25% generic drug price reduction
No ART130,7004.02
Two-pill Generic ART334,80012.1325,200
Branded ART336,20012.14124,700
Three-pill Generic ART337,00011.79DOMINATED
50% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART315,90011.79dominated
Two-pill Generic ART317,80012.1323,100
Branded ART336,20012.141,608,400
75% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART295,00011.79dominated
Two-pill Generic ART300,60012.1321,000
Branded ART336,20012.143,391,200
Probability of late virologic failure (Branded=0.21%, Two-pill Generic=0.45%, Three-
pill Generic=0.45%)
25% generic drug price reduction
No ART130,7004.02
Branded ART336,20012.1425,300
Three-pill Generic ART337,00011.79DOMINATED
Two-pill Generic ART337,60011.94DOMINATED
50% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART315,90011.7923,900
Two-pill Generic ART324,20011.9454,800
Branded ART336,20012.1460,300
75% generic drug price reduction
No ART130,7004.02
Three-pill Generic ART295,00011.7921,200
Two-pill Generic ART310,90011.94107,000
Branded ART336,20012.14127,800

Dominated: A strategy that is more expensive but confers less clinical benefit than some combination of other strategies; DOMINATED: A strategy that is more expensive and confers less clinical benefit than the next least expensive strategy; Antiretroviral therapy; ART; ART: Antiretroviral therapy; USD: United States dollar; QALY: Quality-adjusted life year

*Risk-group adjustments account for differences in non-HIV-related (background) mortality between those at highest risk for HIV and the general population. We considered five sex/risk-groups in our adjustment: men who have sex with men, male and female injection drug users, and male and female high-risk heterosexuals. For each of these groups, we applied a published risk-group specific standardized mortality ratio (SMR) to age- and sex-adjusted non-HIV related mortality rates (50). We then weighted these risk-group-specific mortality rates according to the distribution of risk-groups among HIV-infected individuals in the US (51), as well as to the predicted changes in the distribution over time to get age-, sex-, and risk-adjusted non-HIV mortality rates.

Appendix Figure 1

An external file that holds a picture, illustration, etc.
Object name is nihms-473789-f0001.jpg

Potential annual cost savings in the US with Three-pill or Two-pill Generic ART compared to Branded ART. The potential annual savings on a Two-pill (black bars) or Three-pill (gray bars) Generic ART are compared to Branded ART over a range of generic drug price reductions (%). The horizontal axis shows the range of price reductions, which span from 35% to 95% savings; the base case of 75% savings is indicated by the arrow. The vertical axis shows the amount of money projected to be saved (2009 USD in millions) over one-year horizon. Calculations in this analysis assume that all persons remain on their designated Generic or Branded ART regimen for the first year and do not switch to a subsequent line of therapy before the end of 12 months. (ART: Antiretroviral therapy)


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1. Bangsberg DR, Ragaland K, Monk A, Deeks SG. A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV+ homeless and marginally housed people. AIDS. 2010;24(18):2935–40. [PMC free article] [PubMed]
2. Thompson MA, Mugavero MJ, Amico KR, Cargill VA, Chang LW, Gross R, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: Evidence-based recommendations from an International Association of Physicians in AIDS Care PaneI. Ann Intern Med. 2012;156(11):817–33. [PubMed]
3. Schinazi RE. Assessment of the relative potency of emtricitabine and lamivudine. J Acquir Immune Defic Syndr. 2003;34(2):243–5. [PubMed]
4. Svicher V, Alteri C, Artese A, Forbici F, Santoro MM, Schols D, et al. Different evolution of genotypic resistance profiles to emtricitabine versus lamivudine in tenofovir-containing regimens. J Acquir Immune Defic Syndr. 2010;55(3):336–44. [PubMed]
5. Freedberg K, Losina E, Weinstein M, Paltiel A, Cohen C, Seage G, et al. The cost-effectiveness of combination antiretroviral therapy for HIV Disease. N Engl J Med. 2001;244(11):824–31. [PubMed]
6. Paltiel A, Weinstein M, Kimmel A, Seage G, Losina E, Zhang H, et al. Expanded screening for HIV in the United States - an analysis of cost-effectiveness. N Engl J Med. 2005;352(6):582–95. [PubMed]
7. Paltiel A, Freedberg K, Scott C, Schackman B, Losina E, Wang B, et al. HIV preexposure prophylaxis in the United States: Impact on lifetime infection risk, clinical outcomes, and cost-effectiveness. Clin Infect Dis. 2009;48(6):806–15. [PMC free article] [PubMed]
8. Walensky R, Paltiel A, Losina E, Morris B, Scott C, Rhode E, et al. Test and treat DC: Forecasting the impact of a comprehensive HIV strategy in Washington DC. Clin Infect Dis. 2010;51(4):392–400. [PMC free article] [PubMed]
9. Cost-Effectiveness of Preventing AIDS Complications.
10. Gold M, Siegel J, Russell L, Weinstein M. Cost Effectiveness in Health and Medicine. New York: Oxford University Press. 1996
11. Texas Vital Statistics: Life Tables. Texas Department of State Health Services; 2005.
12. Arias E. United States Life Tables, 2002: National Vital Statistics Reports. Centers for Disease Control and Prevention; 2004. [PubMed]
13. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents - A Working Group of the Office of AIDS Research Advisory Council (OARAC) 2012
14. Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, et al. Co-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-weeks. Lancet. 2012;279(9835):2439–48. [PubMed]
15. Gallant JE, Staszewkski S, Pozniak AL, DeJesus E, Suleiman JMAH, Miller MD, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients. JAMA. 2004;292(2):191–201. [PubMed]
16. Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecog D, et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: A phase II randomised controlled trial. Lancet. 2007;369(9569):1261–9. [PubMed]
17. Johnson M, Grinsztejn B, Rodriguez C, Coco J, DeJesus E, Lazzarin A, et al. Atazanavir plus ritonavir or saquinivir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS. 2005;19(7):685–94. [PubMed]
18. Johnson MA, Gathe JC, Podzamczer D, Molina JM, Naylor CT, Chiu YL, et al. A once-daily lopinavir/ritonavir-based regimen provides noninferior antiviral activity compared with a twice-daily regimen. J Acquir Immune Defic Syndr. 2006;43(2):153–60. [PubMed]
19. Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JVR, S. BD, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: A multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806. [PubMed]
20. Nelson M, Arasteh K, Clotet B, Cooper DA, Henry K, Katlama C, et al. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials. J Acquir Immune Defic Syndr. 2005;40(4):404–12. [PubMed]
21. Gulick R, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008;359(14):1429–41. [PMC free article] [PubMed]
22. Diagnoses of HIV infection and AIDS among adolescents and young adults in the United States and 5 U.S. dependent areas, 2006–2009. HIV Surveillance Supplemental Report. Centers for Disease Control and Prevention; 2012.
23. Althoff KN, Gange SJ, Klein MB, Brooks JT, Hogg RS, Bosch RJ, et al. Late presentation for human immunodeficiency virus care in the United States and Canada. Clin Infect Dis. 2010;50:1512–20. [PMC free article] [PubMed]
24. Multicenter AIDS Cohort Study (MACS) Public Dataset: release PO4. National Technical Information Service; Springfield, VA: 1995.
25. Red Book. Thomson PDR; Montvale, NJ: 2009.
26. Levinson DR. In: Medicaid drug price comparisons: Average manufacturer price to published prices. DHHS, editor. Washington, DC: 2005.
27. New hope for stopping HIV: Testing and medical care save lives. CDC Vital Signs: Centers for Disease Control and Prevention; 2011.
28. McKinnell JA, Willig JH, Westfall AO, Nevin C, Allison JJ, Raper JL, et al. Antiretroviral prescribing patterns in treatment-naive patients in the United States. AIDS Patient Care STDs. 2010;24(2):79–84. [PMC free article] [PubMed]
29. Cutler D, Rosen A, Vijan S. The value of medical spending in the United States, 1960–2000. N Engl J Med. 2006;355:920–7. [PubMed]
30. Gopalappa C, Farnham PG, Hutchinson AB, Sansom SL. Cost-effectiveness of the National HIV/AIDS Strategy (NHAS) goal of increasing linkage to care for HIV-infected persons. J Acquir Immune Defic Syndr. 2012 [PubMed]
31. Hidden Costs, Value Lost: Uninsurance in America. Institute of Medicine of the National Academies; 2003.
32. Battling the virus: A huge, strange drug market. The Economist. 2012
33. Nelson AL, Cohen JT, Greenberg D, Kent DM. Much cheaper, almost as good: Decrementally cost-effective medical innovation. Ann Intern Med. 2009;151:662–7. [PubMed]
34. Linas BP, Wong AY, Schackman BR, Kim AY, Freedberg KA. Cost-effective screening for acute hepatitis C virus infection in HIV-infected men who have sex with men. Clin Infect Dis. 2012 [PMC free article] [PubMed]
35. HIV and Viral Hepatitis Co-Infection. National Alliance of State & Territorial AIDS Directors. 2011
36. ONAP, editor. National HIV/AIDS Strategy for the United States. Washington, DC: 2010.
37. Valdiserri R. Proposed National HIV/AIDS Strategy Implementation Fund. DHHS. 2011
38. The Henry J. Kaiser Family Foundation. 2012
39. Buscher A, Hartman C, Kallen MA, Giordano TP. Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naive HIV patients. Int J STD AIDS. 2012;23(5):351–55. [PMC free article] [PubMed]
40. Berndt ER, Mortimer R, Bhattacharjya A, Parece A, Tuttle E. Authorized generic drugs, price competition, and consumers' welfare. Health Aff. 2007;26(3):790–99. [PubMed]
41. 2012.
42. Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan. U.S. Food and Drug Administration; 2012.
43. Braithwaite RS, Meltzer DO, King JT, Leslie D, Roberts MS. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule. Med Care. 2008;46(4):349–56. [PubMed]
44. Ubel PA, Hirth RA, Chernew ME, Fendrick AM. What is the price of life and why doesn't it increase at the rate of inflation? Arch Intern Med. 2003;163(14):1637–41. [PubMed]
45. Gardner EM, McLees MP, Steiner JF, del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. 2011;52(6):793–800. [PMC free article] [PubMed]
46. Clinical Laboratory Fee Schedule. Centers for Medicare & Medicaid Services; 2009.
47. University HealthSystem Consortium 2006–2008 Cost Data. 2009
48. Gebo KA, Fleishman JA, Conviser R, Reilly ED, Korthuis PT, Moore RD, et al. Racial and gender disparaties in receipt of highly active antiretroviral therapy persist in a multistate sample of HIV patients in 2001. J Acquir Immune Defic Syndr. 2005;38(1):96–103. [PubMed]
49. Bamezai A, Melnick G, Nawathe A. The cost of an emergency department visit and its relationship to emergency department volume. Ann Emerg Med. 2005;45(4):483–89. [PubMed]
50. Seage G, Holte SE, Metzger D, Koblin BA, Gross M, Celum C, et al. Are US populations appropriate for trials of human immunodeficiency virus vaccine? Am J Epidemiol. 2001;153(7):619–26. [PubMed]
51. Prejean J, Song R, Hernandez A, Ziebell R, Green T, Walker F, et al. Estimated incidence in the United States, 2006–2009. PLoS One. 2011;6(8):e17502. [PMC free article] [PubMed]