Biomedical subjects

Kenneth A Freedberg

Publications and source records attributed to Kenneth A Freedberg.

49 records · Page 3Linked to original sources

PubMed2003

Discontinuation from HIV medical care: squandering treatment opportunities.

The purpose of this study was to assess HIV-infected patients' discontinuation of their primary care. One hundred ninety-eight consecutive outpatients were interviewed on initial HIV primary care presentation, assessed after six months about their discontinuation from primary care, and had characteristics associated with discontinuation determined. Primary care was not continued in 20 percent (40/198) of the cases. Cohort characteristics included 25 percent women; 44 percent black, 28 percent white, 25 percent Hispanic; 69 percent with highest yearly income < or = $16,000; 47 percent injection drug users; and median CD4 count 285/microL. Characteristics significantly associated (p < or = 0.05) with discontinuation were higher CD4 count, less education, no history of victimization, previous jail time, and site of medical care. One-fifth of HIV-infected patients did not remain engaged in primary care after establishing this essential link to treatment.

Adult↗

PubMed2002

Cost-effectiveness implications of the timing of antiretroviral therapy in HIV-infected adults.

BACKGROUND: The appropriate time to initiate antiretroviral therapy is controversial for human immunodeficiency virus (HIV)-infected patients with CD4 cell counts between 200/microL and 350/microL and low levels of HIV RNA, potentially leading to barriers to treatment access. OBJECTIVE: To examine the effect of cholesterol changes and fat redistribution symptoms on the clinical benefits and cost-effectiveness of early antiretroviral therapy in these patients. METHODS: We used a state-transition model to compare initiating antiretroviral therapy at CD4 cell counts of 350/microL (early therapy) with initiating therapy at CD4 cell counts of 200/microL (deferred therapy) in patients with HIV RNA levels of 10,000 to 30,000 copies/mL. Data were from randomized clinical trials, cohort studies, and other published literature. RESULTS: If cholesterol changes associated with antiretroviral therapy resulted in a permanent increase in coronary heart disease risk, life expectancy with early therapy was 16.54 years (vs 16.66 years without this risk) and with deferred therapy was 13.73 years (vs 13.80 years without this risk). Early therapy was a more efficient use of resources (ie, dominated) compared with deferred therapy. Early therapy cost $13,000 per quality-adjusted life-year compared with no therapy with or without increased coronary heart disease risk, and $17,000 to $24,000 per quality-adjusted life-year taking into account the quality-of-life reduction in patients with fat distribution symptoms. Early therapy had a higher quality-adjusted life expectancy than deferred therapy as long as this quality-of-life reduction was 70% or less. CONCLUSIONS: Changes in cholesterol or quality of life associated with antiretroviral therapy do not justify limiting access to early HIV treatment. The effect of fat redistribution symptoms on quality of life will determine the optimal choice of early vs deferred therapy for an individual patient.

AIDS-Related Opportunistic Infections↗

PubMed2002

Treatment for primary HIV infection: projecting outcomes of immediate, interrupted, or delayed therapy.

With limited data available on the optimal treatment of primary HIV infection, disease modeling can be used to project clinical outcomes and inform decision makers. The authors developed a simulation model to evaluate the clinical outcomes and life expectancy projections for three primary HIV infection treatment strategies: 1) continuous antiretroviral therapy (ART) initiated at CD4 count <350 cells/mm(3); 2) continuous ART initiated immediately on diagnosis of primary HIV infection; and 3) ART initiated on diagnosis followed by structured treatment interruption. Projected life expectancies for the three strategies were 23.92, 24.46, and 26.07 years, respectively. The impact of key variables was assessed in sensitivity analysis, with the structured treatment interruption strategy remaining the most effective over a broad range of inputs. The immunologic benefit associated with immediate therapy and the potential for antiretroviral resistance due to structured treatment interruption have the most important impact on the optimal strategy. Based on current data, immediate treatment on diagnosis of primary HIV infection followed by structured treatment interruption will likely yield the best outcome. These results can assist decision makers and those planning clinical trials in defining evidence-based performance measures for primary HIV infection treatment and future trials.

Anti-HIV Agents↗

PubMed2002

AIDS Drug Assistance Programs: highlighting inequities in human immunodeficiency virus-infection health care in the United States.

The AIDS Drug Assistance Programs (ADAPs) were founded in 1987 to pay for human immunodeficiency virus (HIV)-related medications in the United States and to help provide prescriptions for HIV-infected patients ineligible for Medicaid who have no private health insurance. As HIV care has shifted from the inpatient to the outpatient arena and as patients live longer because of more-effective antiretroviral therapy, medication costs have increased, and ADAPs have increasingly been operating under emergency measures, with coverage limitations and eligibility restrictions. Because these programs operate at the state level, inequalities in resource distribution to those in need are manifest and appear to contribute to differences in disease outcomes that are based solely on patients' place of residence. Cost-effectiveness analysis would offer a more informed basis for distribution of ADAP resources in an efficient and equitable manner, leading to a standardized national structure.

Acquired Immunodeficiency Syndrome↗

PubMed2002

The relationship of preventable opportunistic infections, HIV-1 RNA, and CD4 Cell counts to chronic mortality.

BACKGROUND: Both HIV-1 RNA and absolute CD4 cell counts have been identified as important predictors of HIV-1 disease progression and mortality. The independent impact of opportunistic infections on the risk of chronic mortality, defined as death beyond 30 days of an opportunistic infection, has not been studied when controlling for HIV-1 RNA. Our objective was to determine the relationship between a history of any of five preventable opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex, toxoplasmosis, cytomegalovirus, and candida esophagitis) and chronic mortality. METHODS: Using the Multicenter AIDS Cohort Study (MACS) public use data set of 2193 HIV-infected men in four U.S. cities, we employed a Cox regression model to estimate the impact of a history of preventable opportunistic infection on chronic mortality while controlling for maximum HIV-1 RNA, CD4 cell count, use of antiretroviral drugs, and age. FINDINGS: The chronic mortality rate among individuals with a history of preventable opportunistic infection was 66.7 per 100 person-years compared with 2.3 per 100 person-years for those without a history of preventable opportunistic infection (RR = 28.4, 95% CI: 24.7-32.8). In the adjusted analysis, the relative hazard of death for those with a history of preventable opportunistic infections was 7.0 (5.8-8.3), whereas antiretroviral therapy was associated with a decreased risk of death (0.37 [0.30-0.44]). We found no association between maximum HIV-1 RNA and chronic mortality. There was statistically significant effect modification between preventable opportunistic infections and CD4 cell count (p <.0001). INTERPRETATION: Preventable opportunistic infections cause not only short-term mortality in HIV-1 disease but appear to have a major impact on chronic mortality.

AIDS-Related Opportunistic Infections↗

PubMed2002

Identifying undiagnosed human immunodeficiency virus: the yield of routine, voluntary inpatient testing.

BACKGROUND: Despite current recommendations for human immunodeficiency virus (HIV) counseling and testing among patients admitted to hospitals with at least a 1% prevalence of HIV infection, an estimated 300 000 people in the United States remain unaware of their HIV infection. METHODS: We implemented the Think HIV program, which offered voluntary HIV counseling and testing to patients admitted to the medical service of a Boston, Mass, teaching hospital. We compared the results of this effort with testing results from a 15-month historical control period. RESULTS: Patients admitted during the program period were 3.4 times more likely to undergo testing for HIV than those admitted during the control period (95% confidence interval [CI], 2.8-4.1). The testing program detected approximately 2 new diagnoses of HIV infection per month, compared with 1 per month during the control period. Patients who underwent testing during the program, and who likely would not have done so without this initiative, had an estimated prevalence of HIV infection of 3.8% (95% CI, 1.8%-5.8%). CONCLUSIONS: Testing efforts for HIV targeted to only symptomatic patients are inadequate to identify the one third of HIV-seropositive people in the United States who are unaware of their infection. We have shown that in a single urban hospital, offering voluntary, routine inpatient HIV counseling and testing can be successful as a screening program by identifying a substantial number of patients with undiagnosed HIV. These patients then can be informed, counseled, and linked to care and treatment. Seventy-two hospitals nationwide have demographics similar to those of the study hospital, suggesting that these results are generalizable to many urban hospitals.

Adult↗

PubMed2002

Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii pneumonia: using simulation modeling to inform clinical guidelines.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis. METHODS: A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/microL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/microL. Data were from randomized controlled trials and other published literature. RESULTS: For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/microL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY. CONCLUSIONS: Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/microL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone.

AIDS-Related Opportunistic Infections↗

PubMed2002

State AIDS Drug Assistance Programs: equity and efficiency in an era of rapidly changing treatment standards.

BACKGROUND: The 54 state AIDS Drug Assistance Programs (ADAP) provide medications to HIV-infected persons with limited resources. Eligibility and coverage vary, raising concerns about health inequities. OBJECTIVE: To compare the relative clinical and economic performance of ADAP programs. RESEARCH DESIGN: A state-transition simulation model of HIV disease was used to explore the clinical consequences and lifetime costs associated with selected state policies. Clinical data came from the Multicenter AIDS Cohort Study, AIDS Clinical Trials Group Protocol 320, and other published randomized trials. Cost data came from the national AIDS Cost and Services Utilization Survey, and the 1999 Red Book. ADAP data came from National Association of State and Territorial AIDS Directors reports and interviews. MEASURES: Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, cost-effectiveness in dollars per quality-adjusted life year (QALY) gained. RESULTS: ADAPs vary considerably in terms of formulary policies, health outcomes, expected costs, and cost-efficiency. Conservative projections, based on a cohort with starting mean CD4 count of 250 cells/microL, yield life expectancies ranging from 5.36 to 6.81 life years (4.69-6.01 quality-adjusted life years [QALYs]). Total per person lifetime direct medical costs range from $81,200 to $112,700; higher costs reflect increased spending on medications. Expected costs per QALY gained range from $7000 to $28,000. Under pessimistic assumptions regarding initial CD4 counts, drug efficacy, and discounting, the most comprehensive policy remains below $33,000/QALY. CONCLUSIONS: Even the most comprehensive ADAPs constitute a cost-effective use of HIV care resources. A uniform, national ADAP formulary warrants consideration.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Lifetime cost of HIV care in France during the era of highly active antiretroviral therapy.

OBJECTIVE: To estimate the treatment and health care costs of HIV infection or AIDS in France during the era of highly active antiretroviral therapy (HAART). DESIGN: We used a clinical database of HIV-infected patients to calculate the resource use and cost of care for different stages of HIV infection. Costs were incorporated into a computer-based, probabilistic simulation model of the natural history and treatment of HIV infection to estimate the lifetime cost of treating patients with HIV disease. SETTING: A northern France HIV clinical cohort. PARTICIPANTS: 1232 HIV-infected patients followed from January 1994 through July 1998. RESULTS: In the absence of an AIDS-defining event, the average total cost of care ranged from 670 euros (1 euro=US $1.19) per person-month in the highest CD4 stratum (>500/microl) to 1060 euros per person-month in the lowest CD4 stratum (< or = 50/microl). The mean cost of care was estimated at 3370 euros per person-month during the initial months around the occurrence of an AIDS-defining event; at 1750 euros per person-month during the period spanning from 2 months after the diagnosis of specific AIDS-defining event to 1 month prior to death; and at 13010 euros per person-month in the final month prior to death. If clinical management of HIV infection began at a CD4 cell count of 378/microl, as in this cohort, the discounted lifetime cost of treating an HIV-infected French patient was estimated at 214000 euros. The undiscounted costs were 309000 euros over a projected life expectancy of 16.4 years. CONCLUSION: The cost of HIV disease varies widely depending upon the stage of illness. These estimates of stage-specific and lifetime costs of HIV care will assist health policy planners in assessing the burden of disease in the era of HAART and projecting future resource requirements.

Adult↗

PubMedDate not supplied

Comparison of health state utilities using community and patient preference weights derived from a survey of patients with HIV/AIDS.

OBJECTIVES: The authors compare health state utilities derived from a national survey of patients with HIV/AIDS to represent community-based preferences with utilities derived from the same survey representing patient preferences; explore the relationships between these utilities and the dimensions of the SF-6D health state classification; and examine the implications of differences in the source of utilities for a cost-effectiveness analysis of early treatment of patients with HIV/AIDS. METHODS: The authors derived community-based standard gamble (SG) utilities using an algorithm developed for the SF-6D health state classification system. The authors derived patient SG utilities from HIV/AIDS patient rating scale self-assessments using a power transformation. Data were from the HIV Cost and Services Utilization Study, a probability sample of 2864 HIV-infected adults receiving care in the United States in 1996. RESULTS: Patient SG utilities were higher than community SG utilities by 4% to 9% (0.979 vs. 0.937, 0.910 vs. 0.841, and 0.845 vs. 0.778; P < 0.001 for all comparisons). In regression analyses, patient SG utilities were less influenced by physical functioning, pain, and mental health dimensions of the SF-6D. The base case results of a cost-effectiveness analysis comparing early antiretroviral therapy to deferred therapy were unaffected by the choice between community ($20,100 per quality-adjusted life year) and patient ($18,400 per quality-adjusted life year) perspectives. The impact of the choice of utilities remained small in sensitivity analyses that varied the influence of treatment side effects on utilities and the initial symptom status of patients. CONCLUSION: There are differences between community and patient utilities for HIV/AIDS health states, although even when treatment side effects are important, these differences may not affect cost-effectiveness ratios.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Utilities derived from visual analog scale scores in patients with HIV/AIDS.

BACKGROUND: Visual analog scale (VAS) scores are used as global quality-of-life indicators and, unlike true utilities (which assess the desirability of health states v. an external metric), are often collected in HIV-related clinical trials. The purpose of this study was to derive and evaluate transformations relating aggregate VAS scores to utilities for current health in patients with HIV/AIDS. METHODS: HIV-specific transformations were developed using linear and nonlinear regression to attain models that best fit mean VAS and standard gamble (SG) utility values directly derived from 299 patients with HIV/AIDS participating in a multicenter study of health values. The authors evaluated the transformations using VAS and SG utility values derived directly from patients in other HIV/AIDS studies. Derived transformations were also compared with published transformations. RESULTS: A simple linear transformation was derived (u = 0.44v + 0.49), as was the exponent for a curvilinear model (u = 1 - [1 - v]1.6), where u = the sample mean utility and v the sample mean VAS score. The curvilinear transformation predicted values within 0.10 of the actual SG utility in 5 of 8 estimates and within 0.05 in 3 of 8 estimates (absolute error ranged from -0.01 to +0.21). The linear transformation performed somewhat better, predicting within 0.10 of the actual SG value in 6 of 8 cases and within 0.05 in 5 of 8 estimates (absolute error ranged from -0.05 to +0.13). An alternative linear model (u = v + 0.018) derived from the literature performed similarly to our linear model (7 of 8 predictions within 0.10, 1 of 8 estimates within 0.05, and absolute error ranging from -0.15 to +0.10), whereas an alternative published curvilinear model (u = 1 - [1 - v]2.3) performed the least well (2 of 8 estimates within 0.10 of the actual values and no estimates within 0.05). CONCLUSIONS: Predicted utilities are a reasonable alternative for use in HIV/AIDS decision analyses and cost-effectiveness analyses. Linear transformations performed better than curvilinear transformations in this context and can be used to convert aggregate VAS scores to aggregate SG values in large HIV/AIDS studies that collect VAS data but not utilities.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Optimal allocation of testing dollars: the example of HIV counseling, testing, and referral.

BACKGROUND: Health screening programs can be represented as a pathway of sequential processes: offering a test, obtaining consent, conducting the test, providing results, and linking to appropriate care. Using the example of HIV testing, the authors explore the optimal targeting of funds within this pathway. METHODS: The authors develop a microsimulation of HIV testing services and decompose the likelihood that an unidentified HIV-infected person will receive care into the probability of testing [P(test)] and the probability of follow-up [P(follow)] defined as returning for results and linking to care. The authors examine the clinical impact and cost-effectiveness of alternative investments in these component probabilities. RESULTS: At 1% undiagnosed HIV prevalence, cost-effectiveness ratios for HIV testing cluster around $33,000/QALY (quality-adjusted life year) gained. A program with a yield of 0.16 via P(test)=0.20 and P(follow)=0.80 has a cost-effectiveness ratio of $32,900/QALY compared with $36,300/QALY for a program where P(test)=0.80 and P(follow)=0.20. Interventions that improve the probability of success in later stages in the testing pathway [P(follow)] are more cost-effective than investments devoted to earlier stages [P(test)]. CONCLUSIONS: Equivalent pathway outcomes in a screening program do not confer equal value. Limited screening resources are best targeted toward returning for results and linkage among those already identified with disease rather than offering testing to additional people.

AIDS Serodiagnosis↗

PubMedDate not supplied

Therapeutic drug monitoring in HIV treatment: a literature review.

PURPOSE: Therapeutic drug monitoring (TDM) is the practice of managing plasma drug concentrations. This intervention can potentially improve inadequate antiretroviral dosing in the treatment of HIV infection. Our objective was to review the evidence regarding TDM in HIV management. METHOD: We searched MEDLINE using the following key words: therapeutic drug monitoring, HIV infection, pharmacokinetics, antiretroviral therapy, protease inhibitors, antiretroviral-naïve, antiretroviral-experienced, and salvage therapy. inclusion criteria required definition of optimal concentration thresholds and measures of treatment effectiveness at these targets. RESULTS: Our search yielded 39 studies. 11 studies met inclusion criteria. 4 studies compared efficacy of TDM to standard of care (SOC) interventions via randomized clinical trials and were grouped as "interventional." 7 studies retrospectively defined thresholds from observed differences in outcome and were grouped as "observational." 3 interventional studies targeted similar indinavir concentrations (Cmin = 0.10-0.15 mg/L). 2 of these studies increased achievement of target serum levels and percentages of undetectable viral load (23%-41%, p < or = .009) with TDM implementation. CONCLUSION: TDM can effectively target antiretroviral threshold concentrations and improve virologic suppression in some cases. Further work is needed to define plasma thresholds and assess the value of TDM in HIV management.

Adult↗