Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Limitations to Treatment Safety and Efficacy
Cost Considerations and Antiretroviral Therapy
Last Updated: November 26, 2018; Last Reviewed: October 25, 2018
Although antiretroviral therapy (ART) is expensive (see Table 17 below), the cost-effectiveness of ART has been demonstrated in analyses of older1 and newer regimens,2,3 as well as for treatment-experienced patients with drug-resistant HIV.4 Given the recommendations for immediate initiation of lifelong treatment and the increasing number of patients taking ART, the Panel now introduces cost-related issues pertaining to medication adherence and cost-containment strategies, as discussed below.
Costs as They Relate to Adherence from a Patient Perspective
Cost sharing: Cost sharing is where the patient is responsible for some of the medication cost burden (usually accomplished via copayments, coinsurance, or deductibles); these costs are often higher for branded medications than for generic medications. In one comprehensive review, increased patient cost sharing resulted in decreased medical adherence and more frequent drug discontinuation; for patients with chronic diseases, increased cost sharing was also associated with increased use of the medical system.5 Conversely, copayment reductions, such as those that might be used to incentivize prescribing of generic drugs, have been associated with improved adherence in patients with chronic diseases.6 Whereas cost sharing disproportionately affects low-income patients, resources (e.g., the Ryan White AIDS Drug Assistance Program [ADAP]) are available to assist eligible patients with copays and deductibles. Given the clear association between out-of-pocket costs for patients with chronic diseases and the ability of those patients to pay for and adhere to medications, clinicians should minimize patients’ out-of-pocket drug-related expenses whenever possible.
Prior authorizations: As a cost-containment strategy, some programs require that clinicians obtain prior authorizations or permission before prescribing newer or more costly treatments rather than older or less expensive drugs. Although there are data demonstrating that prior authorizations do reduce spending, several studies have also shown that prior authorizations result in fewer prescriptions filled and increased nonadherence.7-9 Prior authorizations in HIV care specifically have been reported to cost over $40 each in provider personnel time (a hidden cost) and have substantially reduced timely access to medications.10
Generic ART: The impact of the availability of generic antiretroviral (ARV) drugs on selection of ART in the United States is unknown. Because U.S. patent laws currently limit the coformulation of some generic alternatives to branded drugs, generic options may result in increased pill burden. To the extent that pill burden, rather than drug frequency, results in reduced adherence, generic ART could lead to decreased costs but at the potential expense of worsening virologic suppression rates and poorer clinical outcomes.11,12 Furthermore, prescribing the individual, less-expensive generic components of a branded coformulated product rather than the branded product itself could, under some insurance plans, lead to higher copays—an out-of-pocket cost increase that may reduce medication adherence.
Potential Cost Containment Strategies from a Societal Perspective
Given resource constraints, it is important to maximize the use of resources without sacrificing clinical outcomes. Evidence-based revisions to these guidelines recommend tailored laboratory monitoring for patients with long-term virologic suppression on ART as one possible way to provide overall cost savings. Data suggest that continued CD4 monitoring yields no clinical benefit for patients whose viral loads are suppressed and whose CD4 counts exceed 200 cells/mm3 after 48 weeks of therapy.13 A reduction in laboratory use from biannual to annual CD4 monitoring could save ~$10 million per year in the United States14 (see Laboratory Monitoring). Although this is a small proportion of the overall costs associated with HIV care, such a strategy could reduce patients’ personal expenses if they have deductibles for laboratory tests. The present and future availability of generic formulations of certain ARV drugs, despite the potential caveats of increased pill burden and reduced adherence, offers other money-saving possibilities on a much greater scale. One analysis suggests the possibility of saving approximately $900 million nationally in the first year of switching from a branded fixed-dose combination product to a three-pill regimen containing generic efavirenz.3
In summary, understanding HIV and ART related-costs in the United States is complicated because of the wide variability in medical coverage, accessibility, and expenses across regions, insurance plans, and pharmacies. In an effort to retain excellent clinical outcomes in an environment of cost-containment strategies, providers should remain informed of current insurance and payment structures, ART costs (see Table 16 below for estimates of drugs’ average wholesale prices), discounts among preferred pharmacies, and available generic ART options. Providers should work with patients and their case managers and social workers to understand their patients’ particular pharmacy benefit plans and potential financial barriers to filling their prescriptions. Additionally, providers should familiarize themselves with ARV affordability resources (such as ADAP and pharmaceutical company patient assistance programs for patients who qualify) and refer patients to such assistance if needed.
Table 17. Monthly Average Prices of Commonly Used Antiretroviral Drugs
Prescription drug pricing in the United States involves complex systems of negotiations, rebates, discounts, and reimbursement rates. Much of the information used to determine drug prices is confidential, and prices can vary depending on the purchaser, the type of public or private insurance coverage in use, and the number of generic competitors. In addition, price increases that exceed rates of inflation can trigger additional rebates for Medicaid and 340B Drug Discount Program entities. Table 17 includes three benchmark prices, rounded to the nearest dollar, for commonly used antiretroviral (ARV) drugsa as a general reference for health care providers when considering the cost of HIV treatment. Health care providers should contact patients’ pharmacies or payors regarding actual prices, comparative cost savings, and related formulary restrictions.
Wholesale acquisition cost (WAC) is the list price published by manufacturers for prescription drugs or biologics sold to wholesalers. The WAC price approximates what retail pharmacies pay wholesalers for single-source (e.g., brand-name) drugs. There is a range of WAC prices for generic ARVs, as these are multiple-source products with variable list prices. With increasing competition, actual transactional prices of generic drugs among wholesalers and pharmacies decrease substantially. Average wholesale price (AWP) has historically been used as the basis for setting public (e.g., Medicaid) and private (e.g., commercial insurer) reimbursement rates for pharmacies. Neither WAC nor AWP include variable price concessions along supply and payment chains, including discounts and rebates to wholesalers, pharmacies, federal purchasers (e.g., the Veterans’ Administration), pharmacy benefit managers, commercial insurers, Medicaid, 340B pharmacies, and AIDS Drug Assistance Programs. The availability of these discounts and rebates depends on product demand, market competition, and WAC price increases set by manufacturers.
Maximum prices are assigned to generic products with three or more therapeutically and pharmaceutically equivalent products, as determined by the Food and Drug Administration. This federally established price is the federal upper limit (FUL). Federal Medicaid will reimburse state Medicaid programs up to this limit for multiple-source drugs (plus the dispensing fee); commercial insurers set their own reimbursement upper limits with pharmacies. Whereas WACs and AWPs are generally set annually, FULs are adjusted monthly, particularly for multiple-source drugs with fluctuating pharmacy acquisition costs. In the table below, the FUL for a drug is described as “pending” if a generic drug currently lacks the competition required to trigger a FUL.
|ARV Drug (Generic and Brand Names)||Strength, Formulation||Tablets, Capsules, or mLs per Month||WAC (Monthly)b||AWP (Monthly)b||FUL (As of 9/1/2018)c|
|Nucleoside Reverse Transcriptase Inhibitors (NRTIs)|
|• Generic||300 mg tablet||60 tablets||$150 to $482||$579 to $603||$44|
|• Ziagen||300 mg tablet||60 tablets||$559||$670|
|• Emtriva||200 mg capsules||30 capsules||$537||$644||N/A|
|• Generic||300 mg tablet||30 tablets||$75 to $343||$429 to $430||$83|
|• Epivir||300 mg tablet||30 tablets||$416||$499|
|Tenofovir Disoproxil Fumarate|
|• Generic||300 mg tablet||30 tablets||$58 to $922||$110 to $1,216||Pending|
|• Viread||300 mg tablet||30 tablets||$1,140||$1,368|
|• Generic||300 mg tablet||60 tablets||$36 to $54||$54 to $365||$13|
|NRTI Combination Products|
|• Generic||600 mg/300 mg tablets||30 tablets||$185 to $1,116||$1,395||$356|
|• Epzicom||600 mg/300 mg tablets||30 tablets||$1,292||$1,550|
|• Descovy||25 mg/200 mg tablet||30 tablets||$1,676||$2,011||N/A|
|Tenofovir Disoproxil Fumarate/Emtricitabine|
|• Truvada||300 mg/200 mg tablet||30 tablets||$1,676||$2,011||N/A|
|Tenofovir Disoproxil Fumarate/Lamivudine|
|• Cimduo||300 mg/300 mg tablet||30 tablets||$1,005||$1,207||N/A|
|• Generic||300 mg/150 mg tablet||60 tablets||$134 to $578||$878 to $932||$47|
|• Combivir||300 mg/150 mg tablet||60 tablets||$901||$1,082|
|• Generic||300 mg/300 mg/150 mg tablet||60 tablets||$1,391||$1,738||Pending|
|• Trizivir||300 mg/300 mg/150 mg tablet||60 tablets||$1,610||$1,932|
|Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)|
|• Generic||600 mg tablet||30 tablets||$894||$1,118||Pending|
|• Sustiva||600 mg tablet||30 tablets||$981||$1,177|
|• Pifeltro||100 mg tablet||30 tablets||$1,380||$1,656||N/A|
|• Intelence||200 mg tablet||60 tablets||$1,296||$1,523||N/A|
|• Generic||200 mg tablet||60 tablets||$10 to $45||$648 to $651||$37|
|• Viramune||200 mg tablet||60 tablets||$855||$1,026|
|• Generic XR||400 mg tablet||30 tablets||$246 to $565||$678 to $706||$231|
|• Viramune XR||400 mg tablet||30 tablets||$793||$951|
|• Edurant||25 mg tablet||30 tablets||$1043||$1,252||N/A|
|Protease Inhibitors (PIs)|
|• Generic||200 mg capsule||60 capsules||$878 to $1,264||$1,580 to $1,668||Pending
|• Reyataz||200 mg capsule||60 capsules||$1,463||$1,756|
|• Generic||300 mg capsule||30 capsules||$870 to $1,252||$1,565 to $1,652||Pending|
|• Reyataz||300 mg capsule||30 capsules||$1,449||$1,739|
|• Evotaz||300/150 mg tablet||30 tablets||$1,605||$1,927||N/A|
|• Prezista||600 mg tablet||60 tablets||$1,581||$1,897||N/A|
|• Prezista||800 mg tablet||30 tablets||$1,581||$1,897||N/A|
|• Prezista||100 mg/mL suspension||200 mL||$878||$1,054||N/A|
|• Prezcobix||800 mg/150 mg tablet||30 tablets||$1,806||$2,168||N/A|
|• Kaletra||200 mg/50 mg tablet||120 tablets||$1,024||$1,229||N/A|
|• Aptivus||250 mg capsule||120 capsules||$1,578||$1,894||N/A|
|Integrase Strand Transfer Inhibitors (INSTIs)|
|• Tivicay||50 mg tablet||30 tablets||$1,658||$1,989||N/A|
|• Tivicay||50 mg tablet||60 tablets||$3,315||$3,978||N/A|
|• Isentress||400 mg tablet||60 tablets||$1,500||$1,800||N/A|
|• Isentress HD||600 mg tablet||60 tablets||$1,500||$1,800||N/A|
|• Fuzeon||90 mg injection kit||60 doses (1 kit)||$3,586||$4,303||N/A|
|• Selzentry||150 mg tablet||60 tablets||$1,511||$1,813||N/A|
|• Selzentry||300 mg tablet||60 tablets||$1,511||$1,813||N/A|
|• Selzentry||300 mg tablet||120 tablets||$3,022||$3,626||N/A|
|CD4-Directed Post-Attachment Inhibitor|
|• Trogarzo||200 mg vials||8 vials||$9,080||$10,896||N/A|
|Coformulated Combination Products as Single Tablet Regimens|
|• Biktarvy||50 mg/25 mg/200 mg||30 tablets||$2,946||$3,535||N/A|
|• Symtuza||600 mg/150 mg/10 mg/200 mg||30 tablets||$3,482||$4,178||N/A|
|• Triumeq||50 mg/600 mg/300 mg tablet||30 tablets||$2,805||$3,366||N/A|
|• Juluca||50 mg/25 mg||30 tablets||$2,579||$3,095||N/A|
|Doravirine/Tenofovir Disoproxil Fumarate/Lamivudine|
|• Delstrigo||100 mg/300 mg/300 mg||30 tablets||$2,100||$2,520||N/A|
|Efavirenz/Tenofovir Disoproxil Fumarate/Emtricitabine|
|• Atripla||600 mg/300 mg/200 mg tablet||30 tablets||$2,724||$3,269||N/A|
|Efavirenz/Tenofovir Disoproxil Fumarate/Lamivudine|
|• Symfi||600 mg/300 mg/300 mg tablet||30 tablets||$1,634||$1,961||N/A|
|• Symfi Lo||400 mg/300 mg/300 mg tablet||30 tablets||$1,634||$1,961||N/A|
|• Genvoya||150 mg/150 mg/10 mg/200 mg tablet||30 tablets||$2,946||$3,535||N/A|
|Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/Emtricitabine|
|• Stribild||150 mg/150 mg/300 mg/200 mg tablet||30 tablets||$3,090||$3,708||N/A|
|• Odefsey||25 mg/25 mg/200 mg tablet||30 tablets||$2,681||$3,217||N/A|
|Rilpivirine/Tenofovir Disoproxil Fumarate/Emtricitabine|
|• Complera||25 mg/300 mg/200 mg tablet||30 tablets||$2,681||$3,217||N/A|
|Pharmacokinetic Enhancers (Boosters)|
|• Tybost||150 mg tablet||30 tablets||$219||$264||N/A|
|• Generic||100 mg tablet||30 tablets||$222||$278||Pending
|• Norvir||100 mg tablet||30 tablets||$257||$309|
a The following less commonly used ARV drugs are not included in this table: delavirdine, didanosine, fosamprenavir, indinavir, nelfinavir, saquinavir, and stavudine.
b Source: IBM Watson Health. Micromedex Red Book [database]. 2018. Available at: https://www.micromedexsolutions.com
c Source: Medicare & Medicaid Services. Federal Upper Limits—September 2018 [database]. 2018 September 1. Available at: https://www.medicaid.gov/medicaid/prescription-drugs/pharmacy-pricing/index.html.
- Freedberg KA, Losina E, Weinstein MC, et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med. Mar 15 2001;344(11):824-831. Available at https://www.ncbi.nlm.nih.gov/pubmed/11248160.
- Mauskopf J, Brogan AJ, Talbird SE, Martin S. Cost-effectiveness of combination therapy with etravirine in treatment-experienced adults with HIV-1 infection. AIDS. Jan 28 2012;26(3):355-364. Available at http://www.ncbi.nlm.nih.gov/pubmed/22089378.
- Walensky RP, Sax PE, Nakamura YM, et al. Economic savings versus health losses: the cost-effectiveness of generic antiretroviral therapy in the United States. Ann Intern Med. Jan 15 2013;158(2):84-92. Available at http://www.ncbi.nlm.nih.gov/pubmed/23318310.
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