Cost-effectiveness of tenofovir as first-line antiretroviral therapy in India.

BACKGROUND: World Health Organization guidelines for antiretroviral treatment (ART) in resource-limited settings recommend either stavudine or tenofovir as part of initial therapy. We evaluated the clinical outcomes and cost-effectiveness of first-line ART using tenofovir in India, compared with current practice using stavudine or zidovudine. METHODS: We used a state-transition model of human immunodeficiency virus (HIV) disease to examine strategies using different nucleoside reverse-transcriptase inhibitors, combined with lamivudine and nevirapine, compared with no ART: (1) stavudine, (2) stavudine with substitution by zidovudine after 6 months, (3) zidovudine, and (4) tenofovir. Data were from the Y. R. Gaitonde Centre for AIDS Research and Education in Chennai, India, and published studies. Results. Discounted mean per person survival was 36.9 months (40.2 months undiscounted) with no ART, 115.5 months (145.3) with stavudine-containing ART, 115.7 months (145.6) with stavudine and 6-month zidovudine substitution, 115.8 months (145.6) with zidovudine-containing ART, and 125.8 months (162.0) with initial tenofovir. Discounted lifetime medical costs were $610 with no ART and ranged from $5580 with stavudine-containing ART to $5720 with zidovudine-containing ART. Initial tenofovir had an incremental cost-effectiveness ratio of $670 per year of life saved, compared with no ART, and was more economically efficient than the other regimens. RESULTS: were most sensitive to variations in the costs of first-line tenofovir, access to additional ART after treatment failure, and quality of life adjustment. CONCLUSIONS: Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards, and should be considered for initial therapy for HIV-infected patients in India.

Moral Distress and Attitudes About Timing Related to Comfort Care for Hospitalized Patients: A Survey of Inpatient Providers and Nurses.

CONTEXT: Providing nonbeneficial care at the end of life and delays in initiating comfort care have been associated with provider and nurse moral distress. OBJECTIVE: Evaluate provider and nurse moral distress when using a comfort care order set and attitudes about timing of initiating comfort care for hospitalized patients. METHODS: Cross-sectional survey of providers (physicians, nurse practitioners, and physician assistants) and nurses at 2 large academic hospitals in 2015. Providers and nurses were surveyed about their experiences providing comfort care in an inpatient setting. RESULTS: Two hundred five nurse and 124 provider surveys were analyzed. A greater proportion of nurses compared to providers reported experiencing moral distress "some, most, or all of the time" when using the comfort care order set (40.5% and 19.4%, respectively, P = .002). Over 60% of nurses and providers reported comfort care was generally started too late in a patient's course, with physician trainees (81.4%), as well as providers (80.9%) and nurses (84.0%) < 5 years from graduating professional school most likely to report that comfort care is generally started too late. CONCLUSIONS: The majority of providers and nurses reported that comfort care was started too late in a patient's course. Nurses experienced higher levels of moral distress than providers when caring for patients using a comfort care order set. Further research is needed to determine what is driving this moral distress in order to tailor interventions for nurses and providers.

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy.

BACKGROUND: India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. OBJECTIVE: To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. METHODS: We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/microl (SD 291 cells/microl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. RESULTS: Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 <350 cells/microl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/microl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/microl to <350 cells/microl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. CONCLUSIONS: In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens.

A New Generation of Comfort Care Order Sets: Aligning Protocols with Current Principles.

BACKGROUND: There are few published comfort care order sets for end-of-life symptom management, contributing to variability in treatment of common symptoms. At our academic medical centers, we have observed that rapid titration of opioid infusions using our original comfort care order set's titration algorithm causes increased discomfort from opioid toxicity. OBJECTIVE: The aim of this study was to describe the process and outcomes of a multiyear revision of a standardized comfort care order set for clinicians to treat end-of-life symptoms in hospitalized patients. DESIGN: Our revision process included interdisciplinary group meetings, literature review and expert consultation, beta testing protocols with end users, and soliciting feedback from key committees at our institutions. We focused on opioid dosing and embedding treatment algorithms and guidelines within the order set for clinicians. SETTING: The study was conducted at two large academic medical centers. RESULTS: We developed and implemented a comfort care order set with opioid dosing that reflects current pharmacologic principles and expert recommendations. Educational tools and reference materials are embedded within the order set in the electronic medical record. There are prompts for improved collaboration between ordering clinicians, nurses, and palliative care. CONCLUSIONS: We successfully developed a new comfort care order set at our institutions that can serve as a resource for others. Further evaluation of this order set is needed.

Missed opportunities in providing palliative care for the urban poor: a case discussion.

BACKGROUND: We report the case of a woman with chronic, unexplained symptoms admitted to a large urban hospital, whose clinical status declined rapidly without a definite underlying diagnosis, and who died 2 days after palliative extubation. CONCLUSION: This case illustrates some of the challenges that patients, families, caregivers, and medical teams face in cases of serious life-limiting illness in the disenfranchised poor. Proposed solutions to these challenges include introduction to palliative care earlier in the course of illness and improved access to palliative care in medical safety-net settings.

The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis.

BACKGROUND: In settings with high tuberculosis (TB) prevalence, 15-30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity. OBJECTIVE: To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART. DESIGN: We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities - in all patients or only symptomatic patients - for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/µl; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective. RESULTS: Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient. CONCLUSION: Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective.

Cost-effectiveness of HIV testing referral strategies among tuberculosis patients in India.

BACKGROUND: Indian guidelines recommend routine referral for HIV testing of all tuberculosis (TB) patients in the nine states with the highest HIV prevalence, and selective referral for testing elsewhere. We assessed the clinical impact and cost-effectiveness of alternative HIV testing referral strategies among TB patients in India. METHODS AND FINDINGS: We utilized a computer model of HIV and TB disease to project outcomes for patients with active TB in India. We compared life expectancy, cost, and cost-effectiveness for three HIV testing referral strategies: 1) selective referral for HIV testing of those with increased HIV risk, 2) routine referral of patients in the nine highest HIV prevalence states with selective referral elsewhere (current standard), and 3) routine referral of all patients for HIV testing. TB-related data were from the World Health Organization. HIV prevalence among TB patients was 9.0% in the highest prevalence states, 2.9% in the other states, and 4.9% overall. The selective referral strategy, beginning from age 33.50 years, had a projected discounted life expectancy of 16.88 years and a mean lifetime HIV/TB treatment cost of US$100. The current standard increased mean life expectancy to 16.90 years with additional per-person cost of US$10; the incremental cost-effectiveness ratio was US$650/year of life saved (YLS) compared to selective referral. Routine referral of all patients for HIV testing increased life expectancy to 16.91 years, with an incremental cost-effectiveness ratio of US$730/YLS compared to the current standard. For HIV-infected patients cured of TB, receiving antiretroviral therapy increased survival from 4.71 to 13.87 years. Results were most sensitive to the HIV prevalence and the cost of second-line antiretroviral therapy. CONCLUSIONS: Referral of all patients with active TB in India for HIV testing will be both effective and cost-effective. While effective implementation of this strategy would require investment, routine, voluntary HIV testing of TB patients in India should be recommended.