Clinical and Economic Effects of Widespread Rapid Testing to Decrease SARS-CoV-2 Transmission.

BACKGROUND: The value of frequent, rapid testing to reduce community transmission of SARS-CoV-2 is poorly understood. OBJECTIVE: To define performance standards and predict the clinical, epidemiologic, and economic outcomes of nationwide, home-based antigen testing. DESIGN: A simple compartmental epidemic model that estimated viral transmission, portrayed disease progression, and forecast resource use, with and without testing. DATA SOURCES: Parameter values and ranges as informed by Centers for Disease Control and Prevention guidance and published literature. TARGET POPULATION: U.S. population. TIME HORIZON: 60 days. PERSPECTIVE: Societal; costs included testing, inpatient care, and lost workdays. INTERVENTION: Home-based SARS-CoV-2 antigen testing. OUTCOME MEASURES: Cumulative infections and deaths, number of persons isolated and hospitalized, and total costs. RESULTS OF BASE-CASE ANALYSIS: Without a testing intervention, the model anticipates 11.6 million infections, 119 000 deaths, and $10.1 billion in costs ($6.5 billion in inpatient care and $3.5 billion in lost productivity) over a 60-day horizon. Weekly availability of testing would avert 2.8 million infections and 15 700 deaths, increasing costs by $22.3 billion. Lower inpatient outlays ($5.9 billion) would partially offset additional testing expenditures ($12.5 billion) and workdays lost ($14.0 billion), yielding incremental cost-effectiveness ratios of $7890 per infection averted and $1 430 000 per death averted. RESULTS OF SENSITIVITY ANALYSIS: Outcome estimates vary widely under different behavioral assumptions and testing frequencies. However, key findings persist across all scenarios, with large reductions in infections, mortality, and hospitalizations. Costs per death averted are roughly an order of magnitude lower than commonly accepted willingness-to-pay values per statistical life saved ($5 to $17 million). LIMITATIONS: Analysis was restricted to at-home testing. There are uncertainties concerning test performance. CONCLUSION: High-frequency home testing for SARS-CoV-2 with an inexpensive, imperfect test could contribute to pandemic control at justifiable cost and warrants consideration as part of a national containment strategy. PRIMARY FUNDING SOURCE: National Institutes of Health.

Clinical and Economic Impact of Widespread Rapid Testing to Decrease SARS-CoV-2 Transmission.

BACKGROUND: The value of frequent, rapid testing to reduce community transmission of SARS-CoV-2 is poorly understood. OBJECTIVE: To define performance standards and predict the clinical, epidemiological, and economic outcomes of nationwide, home-based, antigen testing. DESIGN: A simple compartmental epidemic model estimated viral transmission, clinical history, and resource use, with and without testing. DATA SOURCES: Parameter values and ranges informed by Centers for Disease Control guidance and published literature. TARGET POPULATION: United States population. TIME HORIZON: 60 days. PERSPECTIVE: Societal. Costs include: testing, inpatient care, and lost workdays. INTERVENTION: Home-based SARS-CoV-2 antigen testing. OUTCOME MEASURES: Cumulative infections and deaths, numbers isolated and/or hospitalized, and total costs. RESULTS OF BASE-CASE ANALYSIS: Without a testing intervention, the model anticipates 15 million infections, 125,000 deaths, and $10.4 billion in costs ($6.5 billion inpatient; $3.9 billion lost productivity) over a 60-day horizon. Weekly availability of testing may avert 4 million infections and 19,000 deaths, raising costs by $21.5 billion. Lower inpatient outlays ($5.9 billion) would partially offset additional testing expenditures ($12.0 billion) and workdays lost ($13.9 billion), yielding incremental costs per infection (death) averted of $5,400 ($1,100,000). RESULTS OF SENSITIVITY ANALYSIS: Outcome estimates vary widely under different behavioral assumptions and testing frequencies. However, key findings persist across all scenarios: large reductions in infections, mortality, and hospitalizations; and costs per death averted roughly an order of magnitude lower than commonly accepted willingness-to-pay values per statistical life saved ($5-17 million). LIMITATIONS: Analysis restricted to at-home testing and limited by uncertainties about test performance. CONCLUSION: High-frequency home testing for SARS-CoV-2 using an inexpensive, imperfect test could contribute to pandemic control at justifiable cost and warrants consideration as part of a national containment strategy.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

Clinical and Economic Impact of Ibalizumab for People With Multidrug-Resistant HIV in the United States.

BACKGROUND: We projected the clinical outcomes, cost-effectiveness, and budget impact of ibalizumab plus an optimized background regimen (OBR) for people with multidrug-resistant (MDR) HIV in the United States. METHODS: Using the Cost-Effectiveness of Preventing AIDS Complications microsimulation model and a health care sector perspective, we compared 2 treatment strategies for MDR HIV: (1) IBA + OBR-ibalizumab plus OBR and (2) OBR-OBR alone. Ibalizumab efficacy and cohort characteristics were from trial data: mean age 49 years, 85% male, and mean CD4 150/µL. Six-month viral suppression was 50% with IBA + OBR and 0% with OBR. The ibalizumab loading dose cost $10,500, and subsequent ibalizumab injections cost $8400/month; OBR cost $4500/month. Incremental cost-effectiveness ratios (ICERs) were calculated using discounted (3%/year) quality-adjusted life years (QALYs) and costs. ICERs ≤$100,000/QALY were considered cost-effective. We performed sensitivity analysis on key parameters and examined budget impact. RESULTS: In the base case, 5-year survival increased from 38% with OBR to 47% with IBA + OBR. Lifetime costs were $301,700/person with OBR and $661,800/person with IBA + OBR; the ICER for IBA + OBR compared with OBR was $260,900/QALY. IBA + OBR was not cost-effective even with 100% efficacy. IBA + OBR became cost-effective at base case efficacy if ibalizumab cost was reduced by ≥88%. For an estimated 12,000 people with MDR HIV in the United States, IBA + OBR increased care costs by $1.8 billion (1.5% of total treatment budget) over 5 years. CONCLUSIONS: For people with MDR HIV lacking other treatment options, ibalizumab will substantially increase survival when effective. Although adding ibalizumab to OBR is not cost-effective, the low number of eligible patients in the United States makes the budget impact relatively small.

Clinical Impact and Cost-effectiveness of Genotype Testing at Human Immunodeficiency Virus Diagnosis in the United States.

BACKGROUND: US guidelines recommend genotype testing at human immunodeficiency virus (HIV) diagnosis ("baseline genotype") to detect transmitted drug resistance (TDR) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors. With integrase strand inhibitor (INSTI)-based regimens now recommended as first-line antiretroviral therapy (ART), the of baseline genotypes is uncertain. METHODS: We used the Cost-effectiveness of Preventing AIDS Complications model to examine the clinical impact and cost-effectiveness of baseline genotype compared to no baseline genotype for people starting ART with dolutegravir (DTG) and an NRTI pair. For people with no TDR (83.8%), baseline genotype does not alter regimen selection. Among people with transmitted NRTI resistance (5.8%), baseline genotype guides NRTI selection and informs subsequent ART after adverse events (DTG AEs, 14%). Among people with transmitted NNRTI resistance (7.2%), baseline genotype influences care only for people with DTG AEs switching to NNRTI-based regimens. The 48-week virologic suppression varied (40%-92%) depending on TDR. Costs included $320/genotype and $2500-$3000/month for ART. RESULTS: Compared to no baseline genotype, baseline genotype resulted in <1 additional undiscounted quality-adjusted life-day (QALD), cost an additional $500/person, and was not cost-effective (incremental cost-effectiveness ratio: $420 000/quality-adjusted life-year). In univariate sensitivity analysis, clinical benefits of baseline genotype never exceeded 5 QALDs for all newly diagnosed people with HIV. Baseline genotype was cost-effective at current TDR prevalence only under unlikely conditions, eg, DTG-based regimens achieving ≤50% suppression of transmitted NRTI resistance. CONCLUSIONS: With INSTI-based first-line regimens in the United States, baseline genotype offers minimal clinical benefit and is not cost-effective.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel.

Importance: Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. Objective: To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. Evidence Review: New evidence collected since the International Antiviral Society-USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. Findings: ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. Conclusions and Relevance: Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

The Clinical and Economic Impact of Attaining National HIV/AIDS Strategy Treatment Targets in the United States.

Background: The US National HIV/AIDS Strategy (NHAS) aims for 72% (90% diagnosed times 80% of those virally suppressed) viral suppression among persons with human immunodeficiency virus (HIV) by 2020. We examined the clinical and economic impact of reaching this target, in the general US population and among black men who have sex with men (MSM), the group with the highest HIV prevalence. Methods: Using a mathematical simulation, we project the 5- and 20-year clinical outcomes, costs, and incremental cost-effectiveness ratios for (1) Current Pace of detection, linkage, retention, and virologic suppression and (2) NHAS investments in expanded testing ($24-$74 per test) and adherence ($400 per person-year), calibrated to achieve 72% suppression by 2020. We examined alternative rates of testing, retention, and suppression and the efficacy and cost of adherence interventions. Results: Compared with Current Pace over 20 years, NHAS averted 280000 HIV transmissions (80000 in black MSM) and 199000 (45000) deaths and saved 2138000 (453000) years of life, while increasing costs by 23%. The incremental cost-effectiveness ratio for NHAS compared with Current Pace was $68900 per quality-adjusted life-year ($38300 for black MSM) and was most sensitive to antiretroviral therapy costs. Conclusions: Reaching NHAS targets would yield substantial clinical benefits and be cost-effective in both the general US and black MSM populations.

Setting Performance Standards for a Cost-Effective Human Immunodeficiency Virus Cure Strategy in South Africa.

BACKGROUND: Reports of a single case of human immunodeficiency virus (HIV) eradication suggest that elimination of HIV from individuals is possible. Anticipating both increased research funding and the development of effective, durable cure technologies, we describe the circumstances under which a cure might improve survival and be cost-effective in South Africa. METHODS: We adapted a simulation model comparing a hypothetical cure strategy ("Cure") to the standard of care, lifetime antiretroviral therapy ("LifetimeART") among adherent South Africans (58% female; mean age 33.8 years; mean CD4 257/µL; virologic suppression ≥1 year). We portrayed cure as a single intervention, producing sustained viral eradication without ART. We considered both a plausible, more imminently achievable "Baseline Scenario" and a more aspirational "Optimistic Scenario". Inputs (Baseline/Optimistic) included the following: 50%/75% efficacy; 0.6%/0.0% fatal toxicity; 0.37%/0.085% monthly relapse over 5 years (0.185%/0.0425% per month thereafter); and $2000/$500 cost. These inputs were varied extensively in sensitivity analysis. RESULTS: At baseline, Cure was "dominated," yielding lower discounted life expectancy (19.31 life-years [LY] vs 19.37 LY) and greater discounted lifetime costs ($13 800 vs $13 700) than LifetimeART. Under optimistic assumptions, Cure was "cost-saving," producing greater survival (19.91 LY) and lower lifetime costs ($11 000) than LifetimeART. Findings were highly sensitive to data assumptions, leaving little middle ground where a tradeoff existed between improved survival and higher costs. CONCLUSIONS: Only under the most favorable performance assumptions will an HIV cure strategy prove clinically and economically justifiable in South Africa. The scientific pursuit of a cure should not undermine continued expansions of access to proven, effective, and cost-effective ART.

Should We Be Testing for Baseline Integrase Resistance in Patients Newly Diagnosed With Human Immunodeficiency Virus?

Background: Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR testing"), although this class of drugs is a component of most recommended first-line regimens. Methods: We compared the 96-week clinical outcomes and cost-effectiveness of 2 strategies: no IR testing vs IR testing performed at human immunodeficiency virus (HIV) diagnosis. The base case prevalence of transmitted integrase strand transfer inhibitor (INSTI)-resistant (INSTI-R) virus is estimated at 0.1%. With no IR testing, all patients start dolutegravir (DTG)-based ART after genotype; 12-week suppression rates are 90% (INSTI-susceptible [INSTI-S] virus) and 35% (INSTI-R virus). Those not suppressed at 12 weeks undergo IR testing; if diagnosed with INSTI-R virus, they change to ritonavir-boosted darunavir (DRV/r)-based ART. With IR testing, all patients are diagnosed with INSTI-S/INSTI-R virus prior to ART initiation and start DTG- or DRV/r-based regimens, respectively. Costs include IR tests (175 US dollars [USD]) and ART (41100-44900 USD/year). We examined the impact of key parameters in sensitivity analyses. Results: IR testing resulted in worse clinical outcomes compared to no IR testing and increased costs by 200 USD/person/year. Prevalence of transmitted INSTI-R virus did not affect the favored strategy. No IR testing remained clinically preferred unless DTG suppression of INSTI-R virus was <20% or 96-week DRV/r suppression was >92%. If quality of life was worse with DRV/r- than DTG-based ART, no IR testing was clinically preferred over an even broader range of parameters. Conclusions: In patients with newly diagnosed HIV, IR testing is projected to result in worse outcomes and is not cost-effective. Pretreatment assessment for INSTI resistance should not be recommended in treatment guidelines.

The Cost-effectiveness and Budget Impact of 2-Drug Dolutegravir-Lamivudine Regimens for the Treatment of HIV Infection in the United States.

BACKGROUND: Recommended human immunodeficiency virus (HIV) treatment regimens in the United States contain 3 antiretroviral agents, costing >$30 000/person/year. Pilot studies are evaluating the efficacy of dual therapy with dolutegravir (DTG) and lamivudine (3TC). We examined the potential cost-effectiveness and budget impact of DTG + 3TC regimens in the United States. METHODS: Using a mathematical model, we projected the clinical and economic outcomes of antiretroviral therapy (ART)-naive patients under 4 strategies: (1) no ART (for modeling comparison); (2) 2-drug: initial regimen of DTG + 3TC; (3) induction-maintenance: 48-week induction regimen of 3 drugs (DTG/abacavir [ABC]/3TC), followed by DTG + 3TC maintenance if virologically suppressed; and (4) standard of care: 3-drug regimen of DTG/ABC/3TC. Strategy-dependent model inputs, varied widely in sensitivity analyses, included 48-week virologic suppression (88%-93%), subsequent virologic failure (0.1%-0.6%/month), and Medicaid-discounted ART costs ($15 200-$39 600/year). A strategy was considered cost-effective if its incremental cost-effectiveness ratio (ICER) was <$100 000/quality-adjusted life-year (QALY). RESULTS: The 3 ART strategies had the same 5-year survival rates (90%). The ICER was $22 500/QALY for induction-maintenance and >$500 000/QALY for standard of care. Two-drug was the preferred strategy only when DTG + 3TC 48-week virologic suppression rate exceeded 90%. With 50% uptake of either induction-maintenance or 2-drug for ART-naive patients, cost savings totaled $550 million and $800 million, respectively, within 5 years; savings reached >$3 billion if 25% of currently suppressed patients were switched to DTG + 3TC maintenance. CONCLUSIONS: Should DTG + 3TC demonstrate high rates of virologic suppression, this regimen will be cost-effective and would save >$500 million in ART costs in the United States over 5 years.

Prioritizing HIV comparative effectiveness trials based on value of information: generic versus brand-name ART in the US.

BACKGROUND: Value of Information (VOI) analysis examines whether to acquire information before making a decision. We introduced VOI to the HIV audience, using the example of generic antiretroviral therapy (ART) in the US. METHODS AND FINDINGS: We used a mathematical model and probabilistic sensitivity analysis (PSA) to generate probability distributions of survival (in quality-adjusted life years, QALYs) and cost for three potential first-line ART regimens: three-pill generic, two-pill generic, and single-pill branded. These served as input for a comparison of two hypothetical two-arm trials: three-pill generic versus single-pill branded; and two-pill generic versus single-pill branded. We modeled pre-trial uncertainty by defining probability distributions around key inputs, including 24-week HIV-RNA suppression and subsequent ART failure. We assumed that, without a trial, patients received the single-pill branded strategy. Post-trial, we assumed that patients received the most cost-effective strategy. For both trials, we quantified the probability of changing to a generic-based regimen upon trial completion and the expected VOI in terms of improved health outcomes and costs. Assuming a willingness to pay (WTP) threshold of $100 000/QALY, the three-pill trial led to more treatment changes (84%) than the two-pill trial (78%). Estimated VOI was $48 000 (three-pill trial) and $35 700 (two-pill trial) per future patient initiating ART. CONCLUSIONS: A three-pill trial of generic ART is more likely to lead to post-trial treatment changes and to provide more value than a two-pill trial if policy decisions are based on cost-effectiveness. Value of Information analysis can identify trials likely to confer the greatest impact and value for HIV care.

The clinical role and cost-effectiveness of long-acting antiretroviral therapy.

BACKGROUND: Long-acting antiretroviral therapy (LA-ART) is currently under development and could improve outcomes for human immunodeficiency virus (HIV)-infected individuals with poor daily ART adherence. METHODS: We used a computer simulation model to evaluate the cost-effectiveness of 3 LA-ART strategies vs daily oral ART for all: (1) LA-ART for patients with multiple ART failures; (2) second-line LA-ART for those failing first-line therapy; and (3) first-line LA-ART for ART-naive patients. We calculated the maximum annual cost of LA-ART at which each strategy would be cost-effective at a willingness to pay of $100 000 per quality-adjusted life-year. We assumed HIV RNA suppression on daily ART ranged from 0% to 91% depending on adherence, vs 91% suppression on LA-ART regardless of daily ART adherence. In sensitivity analyses, we varied adherence, efficacy of LA-ART and daily ART, and loss to follow-up. RESULTS: Relative to daily ART, LA-ART increased overall life expectancy by 0.15-0.24 years, and by 0.51-0.89 years among poorly adherent patients, depending on the LA-ART strategy. LA-ART after multiple failures became cost-effective at an annual drug cost of $48 000; in sensitivity analysis, this threshold varied from $40 000-$70 000. Second-line LA-ART and first-line LA-ART became cost-effective at an annual drug cost of $26 000-$31 000 and $24 000-$27 000, vs $28 000 and $25 000 for current second-line and first-line regimens. CONCLUSIONS: LA-ART could improve survival of HIV patients, especially those with poor daily ART adherence. At an annual cost of $40 000-$70 000, LA-ART will offer good value for patients with multiple prior failures. To be a viable option for first- or second-line therapy, however, its cost must approach that of currently available regimens.

Cost-effectiveness of genotype testing for primary resistance in Brazil.

OBJECTIVE: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. DESIGN: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). METHODS: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as "cost-effective" compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12,300. RESULTS: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45,000 to $44,770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges. CONCLUSIONS: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil.

HIV cure strategies: how good must they be to improve on current antiretroviral therapy?

BACKGROUND: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). METHODS: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. RESULTS: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. CONCLUSIONS: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.

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

BACKGROUND: U.S. HIV treatment guidelines recommend branded once-daily, 1-pill efavirenz-emtricitabine-tenofovir as first-line antiretroviral therapy (ART). With the anticipated approval of generic efavirenz in the United States, a once-daily, 3-pill alternative (generic efavirenz, generic lamivudine, and tenofovir) will decrease cost but may reduce adherence and virologic suppression. OBJECTIVE: To assess the clinical effect, costs, and cost-effectiveness of a 3-pill, generic-based regimen compared with a branded, coformulated regimen and to project the potential national savings in the first year of a switch to generic-based ART. DESIGN: Mathematical simulation of HIV disease. SETTING: United States. PATIENTS: HIV-infected persons. INTERVENTION: No ART (for comparison); 3-pill, generic-based ART; and branded ART. MEASUREMENTS: Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). RESULTS: Compared with no ART, generic-based ART has an ICER of $21,100/QALY. Compared with generic-based 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 U.S. patients start or switch to generic-based ART, are $920 million. Most plausible assumptions about generic-based ART efficacy and costs lead to branded ART ICERs greater than $100,000/QALY. LIMITATION: The efficacy and price reduction associated with generic drugs are unknown, and estimates are intended to be conservative. CONCLUSION: Compared with a slightly less effective generic-based regimen, the cost-effectiveness of first-line branded ART exceeds $100,000/QALY. Generic-based ART in the United States could yield substantial budgetary savings to HIV programs. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Cost-effectiveness analysis of UGT1A1 genetic testing to inform antiretroviral prescribing in HIV disease.

BACKGROUND: Homozygosity for UGT1A1*28/*28 has been reported to be associated with atazanavir-associated hyperbilirubinaemia and premature atazanavir discontinuation. We assessed the potential cost-effectiveness of UGT1A1 testing to inform the choice of an initial protease-inhibitor-containing regimen in antiretroviral therapy (ART)-naive individuals. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications computer simulation model to project quality-adjusted life years (QALYs) and lifetime costs (2009 USD) for atazanavir-based ART with or without UGT1A1 testing, using darunavir rather than atazanavir when indicated. We assumed the UGT1A1-associated atazanavir discontinuation rate reported in the Swiss HIV Cohort Study (a *28/*28 frequency of 14.9%), equal efficacy and cost of atazanavir and darunavir and a genetic assay cost of $107. These parameters, as well as the effect of hyperbilirubinaemia on quality of life and loss to follow up, were varied in sensitivity analyses. Costs and QALYs were discounted at 3% annually. RESULTS: Initiating atazanavir-based ART at CD4(+) T-cell counts <500 cells/µl without UGT1A1 testing had an average discounted life expectancy of 16.02 QALYs and $475,800 discounted lifetime cost. Testing for UGT1A1 increased QALYs by 0.49 per 10,000 patients tested and was not cost-effective (>$100,000/QALY). Testing for UGT1A1 was cost-effective (<$100,000/QALY) if assay cost decreased to $10, or if avoiding hyperbilirubinaemia by UGT1A1 testing reduced loss to follow-up by 5%. If atazanavir and darunavir differed in cost or efficacy, testing for UGT1A1 was not cost-effective under any scenario. CONCLUSIONS: Testing for UGT1A1 may be cost-effective if assay cost is low and if testing improves retention in care, but only if the comparator ART regimens have the same drug cost and efficacy.