[show abstract][hide abstract] ABSTRACT: The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz-related teratogenicity) associated with using efavirenz in HIV-infected women of childbearing age in the USA.
We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz-based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor-based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100,000 women, we incorporated literature-based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women.
Survival for HIV-infected women who received an efavirenz-based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non-efavirenz-based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100,000 exposed women, compared with 72.46/100,000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS-related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz-exposed women.
Use of non-efavirenz-based initial ART in HIV-infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision-making regarding efavirenz use presents a trade-off between these two risks; this study can inform discussions between patients and health care providers.
HIV Medicine 02/2011; 12(2):97-108. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Resistance testing in HIV disease may provide long-term benefits that are not evident from short-term data. Our objectives were to estimate the long-term effectiveness, cost and cost-effectiveness of genotype testing in patients with extensive antiretroviral exposure.
We used an HIV simulation model to estimate the long-term effectiveness and cost-effectiveness of genotype testing. Clinical data incorporated into the model were from NARVAL, a randomized trial of resistance testing in patients with extensive antiretroviral exposure, and other randomized trials. Each simulated patient was eligible for up to three sequential regimens of antiretroviral therapy (i.e. two additional regimens beyond the trial-based regimen) using drugs not available at the time of the study, such as lopinavir/ritonavir, darunavir/ritonavir and enfuvirtide.
In the long term, projected undiscounted life expectancy increased from 132.2 months with clinical judgement alone to 147.9 months with genotype testing. Median survival was estimated at 11.9 years in the resistance testing arm vs 10.4 years in the clinical judgement alone arm. Because of increased survival, the projected lifetime discounted cost of genotype testing was greater than for clinical judgement alone (euro313,900 vs euro263,100; US$399,000 vs US$334,400). Genotype testing cost euro69,600 (US$88,500) per quality-adjusted life year gained compared with clinical judgement alone.
In patients with extensive prior antiretroviral exposure, genotype testing is likely to increase life expectancy in the long term as a result of the increased likelihood of receiving two active new drugs. Genotype testing is associated with cost-effectiveness comparable to that of strategies accepted in patients with advanced HIV disease, such as enfuvirtide use.
HIV Medicine 11/2007; 8(7):439-50. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: To estimate incidence rates of opportunistic diseases (ODs) and mortality for patients with and without a history of OD among HIV-infected patients in Côte d'Ivoire.
Using incidence density analysis, we estimated rates of ODs and chronic mortality by CD4 count in patients in a cotrimoxazole prophylaxis trial in Abidjan before the highly active antiretroviral therapy (HAART) era. Chronic mortality was defined as death without a history of OD or death more than 30 days after an OD diagnosis. We used Poisson's regression to examine the effect of OD history on chronic mortality after adjusting for age, gender, and current CD4 count.
Two hundred and seventy patients (40% male, mean age 33 years, median baseline CD4 count 261 cells/microl) were followed up for a median of 9.5 months. Bacterial infections and tuberculosis were the most common severe ODs. Of 47 patients who died, 9 (19%) died within 30 days of an OD, 26 (55%) died more than 30 days after an OD, and 12 (26%) died with no OD history. The chronic mortality rate was 31.0/100 person-years for those with an OD history, and 11.1/100 person-years for those with no OD history (rate ratio (RR) 2.81, 95% confidence interval (CI): 1.43 - 5.54). Multivariate analysis revealed that OD history remained an independent predictor of mortality (RR 2.15, 95% CI: 1.07 - 4.33) after adjusting for CD4 count, age and gender.
Before the HAART era, a history of OD was associated with increased chronic HIV mortality in Côte d'Ivoire, even after adjusting for CD4 count. These results provide further evidence supporting OD prophylaxis in HIV-infected patients.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 07/2006; 96(6):526-9. · 1.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: This paper investigates the impact of quality-of-life adjustment on cost-effectiveness analyses, by comparing ratios from published studies that have reported both incremental costs per (unadjusted) life-year and per quality-adjusted life-year for the same intervention.
A systematic literature search identified 228 original cost-utility analyses published prior to 1998. Sixty-three of these analyses (173 ratio pairs) reported both cost/LY and cost/QALY ratios for the same intervention, from which we calculated medians and means, the difference between ratios (cost/LY minus cost/QALY) and between reciprocals of the ratios, and cost/LY as a percentage of the corresponding cost/QALY ratio. We also compared the ratios using rank-order correlation, and assessed the frequency with which quality-adjustment resulted in a ratio crossing the widely used cost-effectiveness thresholds of 20, 000 US dollars, 50,000 US dollars, and 100,000 US dollars/QALY or LY.
The mean ratios were 69,100 US dollars/LY and 103,100 US dollars/QALY, with corresponding medians of 24,600 US dollars/LY and 20,400 US dollars/QALY. The mean difference between ratios was approximately -34,300 US dollars (median difference: 1300 US dollars), with 60% of ratio pairs differing by 10,000 US dollars/year or less. Mean difference between reciprocals was 59 (QA)LYs per million dollars (median: 2.1). The Spearman rank-order correlation between ratio types was 0.86 (p<0.001). Quality-adjustment led to a ratio moving either above or below 50,000 US dollars/LY (or QALY) in 8% of ratio pairs, and across 100,000 US dollars in 6% of cases.
In a sizable fraction of cost-utility analyses, quality adjusting did not substantially alter the estimated cost-effectiveness of an intervention, suggesting that sensitivity analyses using ad hoc adjustments or 'off-the-shelf' utility weights may be sufficient for many analyses. The collection of preference weight data should be subjected to the same scrutiny as other data inputs to cost-effectiveness analyses, and should only be under-taken if the value of this information is likely to be greater than the cost of obtaining it.
Health Economics 06/2004; 13(5):429-36. · 2.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: Herpes simplex virus type 2 (HSV-2) is the most common cause of ulcerative genital disease in the United States, but infection is commonly unrecognised. Serological screening tests could identify discordantly infected couples and permit targeted interventions to limit HSV-2 transmission. Our objective was to evaluate the projected cost effectiveness of strategies to prevent HSV-2 transmission in couples with no history of HSV-2 infection.
We created a mathematical model to simulate the natural history and costs of HSV-2 transmission, and the expected impact of HSV-2 prevention strategies in monogamous, heterosexual couples. Strategies evaluated included (i) no screening; (ii) universal condom use; and (iii) serological screening for HSV-2 with condom use targeted to discordant couples. Screening tests considered included western blot (WB), ELISA, and ELISA with confirmation of positive test results using WB (ELISA-->WB).
Compared to no screening, the use of ELISA-->WB prevented 38 future infections per 1000 couples, with a cost effectiveness ratio of $8200 per infection averted. The use of WB in all couples had an incremental cost effectiveness ratio of $63 600 per infection averted. Strategies of ELISA alone and universal condom use were not cost effective. The cost effectiveness of ELISA-->WB improved with increasing prevalence of HSV-2, but worsened with decreasing condom compliance. Screening with ELISA alone was a reasonable strategy only when ELISA specificity increased to 99%.
Serological screening for unrecognised HSV-2 infection in monogamous, heterosexual couples is expected to decrease the incidence of HSV-2 infection, but increase healthcare costs. For couples choosing to be screened, a two step testing strategy (ELISA-->WB) is recommended. Recommendations for a national policy to conduct serological screening will depend on the value placed on averting an incident HSV-2 infection.
[show abstract][hide abstract] ABSTRACT: A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMZ) increased per-person lifetime costs from euro 185,600 to euro 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of euro 18,700 per quality-adjusted life-year (euro/QALY) gained. Compared with use of TMP-SMZ alone, use of TMP-SMZ plus azithromycin cost euro 23,900/QALY gained; adding fluconazole cost an additional euro 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded euro 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority.
[show abstract][hide abstract] ABSTRACT: To determine the cost effectiveness of incorporating molecular testing for high-risk types of human papillomavirus into a cervical cancer screening program for women infected with the human immunodeficiency virus (HIV).
We developed a Markov model to simulate the natural history of cervical cancer precursor lesions in HIV-infected women. Probabilities of progression and regression of cervical lesions were conditional on transient or persistent infection with human papillomavirus, as well as stage of HIV and effectiveness of antiretroviral therapy. Incorporating data from prospective cohort studies, national databases, and published literature, the model was used to calculate quality-adjusted life expectancy, life expectancy, lifetime costs, and incremental cost-effectiveness ratios for two main strategies: targeted screening-human papillomavirus testing is added to the initial two cervical cytology smears obtained after an HIV diagnosis and subsequent screening intervals are modified based on the test results; and universal screening-no testing for human papillomavirus is performed, and a single cytology screening interval is applied to all women.
In HIV-infected women on anti-retroviral therapy, a targeted screening strategy in which cervical cytology screening was conducted every 6 months for women with detected human papillomavirus DNA, and annually for all others, cost $10,000 to $14,000 per quality-adjusted life year gained compared with no screening. A universal screening strategy consisting of annual cervical cytology for all women was 15% less effective and had a less attractive cost-effectiveness ratio. Targeted screening remained economically attractive in multiple sensitivity analyses, although when the overall incidence of cervical cancer precursor lesions was lowered by 75%, the screening interval for women with detected human papillomavirus DNA could be widened to 1 year.
Adding human papillomavirus testing to the two cervical cytology smears obtained in the year after an HIV diagnosis, and modifying subsequent cytology screening intervals based on the results, appears to be an effective and cost-effective modification to current recommendations for annual cytology screening in HIV-infected women.
The American Journal of Medicine 09/2001; 111(2):140-9. · 4.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: Motor vehicle crashes are the leading cause of death in children ages 5 to 14. Children seated in the front seats of vehicles are at increased risk of death and injury in crashes, particularly in vehicles with passenger-side air bags. This study identifies factors associated with the seating of children in the front seats of vehicles involved in fatal crashes between 1990 and 1998.
Using 1990 to 1998 data from the Fatal Analysis Reporting System, a US census of motor vehicle crashes involving a fatality, multivariable logistic regression was used to model the association between child seating behavior and vehicle, driver, and occupant characteristics.
The proportion of vehicles carrying children in the front declined from 42% to 31% over the 9-year period. Controlling for driver and vehicle characteristics, the risk of front-seating declined between 1990 and 1998, and this risk was smaller in vehicles carrying only younger children (</=6 years) than in those carrying older children. In the 3 years after the introduction of dual air bags into a significant proportion of the passenger fleet in late 1995, dual air bags were associated with fewer children being seated in the front seat. By the end of 1998, traveling in a vehicle with dual air bags and only children age 6 or younger was associated with a 95% lower chance of a child being seated in the front (odds ratio = 0.05; 95% confidence interval: 0.04-0.08). An important factor in safer seating position was the presence of multiple passengers, especially an older one, and children were at higher risk of front-seating when they traveled alone with the driver.
The 1990s saw a decline in front-seating of children in vehicles involved in fatal crashes among all types of vehicles and drivers. Although this trend is encouraging, children ages 6 to 12 and children traveling alone with the driver remain at higher risk of being seated in the front. These traveling situations should be targeted for behavioral safety interventions to improve child motor vehicle safety.
[show abstract][hide abstract] ABSTRACT: Clinical guidelines for the prevention of opportunistic infections in human immunodeficiency virus (HIV)-infected individuals have been developed on the basis of natural history data collected in the USA. The objective of this study was to estimate the incidence of primary opportunistic infections in HIV-infected individuals in geographically distinct cohorts in France.
We conducted our study on 2664 HIV-infected patients from the Tourcoing AIDS Reference Centre and the hospital-based information system of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine enrolled from January 1987 to September 1995 and followed through December 1995. We estimated: (1) CD4-adjusted incidence rates of seven primary opportunistic infections in the absence of prophylaxis for that specific infection or any antiretroviral drugs other than zidovudine; and (2) CD4 lymphocyte count decline.
The highest incidence rates for all opportunistic infections studied occurred in patients with CD4 counts < 200/microl. With CD4 counts < 50/microl, the most common opportunistic infections were toxoplasmic encephalitis (12.6 per 100 person-years) and Pneumocystis carinii pneumonia (11.4 per 100 person-years). Mycobacterium tuberculosis was the least common opportunistic infection (< 5.0/100 person-years). Even with CD4 counts > 300/microl, cases of Pneumocystis carinii pneumonia and toxoplasmic encephalitis were reported. The mean CD4 lymphocyte decline per month was 4.6 cells/microl. There was a significant association between HIV risk behaviour and the incidence of cytomegalovirus infection, between calendar year and the incidence of Pneumocystis carinii pneumonia, toxoplasmic encephalitis and Candida esophagitis, and between geographical area and the incidence of Pneumocystis carinii pneumonia and cytomegalovirus infection.
Geographical differences exist in the incidence of HIV-related opportunistic infections. These results can be used to define local priorities for prophylaxis of opportunistic infections.
International Journal of Epidemiology 08/2001; 30(4):864-71. · 6.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cervical cancer is a leading cause of cancer-related death among women in developing countries. In such low-resource settings, cytology-based screening is difficult to implement, and less complex strategies may offer additional options.
To assess the cost-effectiveness of several cervical cancer screening strategies using population-specific data.
Cost-effectiveness analysis using a mathematical model and a hypothetical cohort of previously unscreened 30-year-old black South African women. Screening tests included direct visual inspection (DVI) of the cervix, cytologic methods, and testing for high-risk types of human papillomavirus (HPV) DNA. Strategies differed by number of clinical visits, screening frequency, and response to a positive test result. Data sources included a South African screening study, national surveys and fee schedules, and published literature.
Years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (cost per YLS).
When analyzing all strategies performed as a single lifetime screen at age 35 years compared with no screening, HPV testing followed by treatment of screen-positive women at a second visit, cost $39/YLS (27% cancer incidence reduction); DVI, coupled with immediate treatment of screen-positive women at the first visit was next most effective (26% cancer incidence reduction) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit was least effective (19% cancer incidence reduction) at a cost of $81/YLS. For any given screening frequency, when strategies were compared incrementally, HPV DNA testing generally was more effective but also more costly than DVI, and always was more effective and less costly than cytology. When comparing all strategies simultaneously across screening frequencies, DVI was the nondominated strategy up to a frequency of every 3 years (incremental cost-effectiveness ratio, $460/YLS), and HPV testing every 3 years (incremental cost-effectiveness ratio, $11 500/YLS) was the most effective strategy.
Cervical cancer screening strategies that incorporate DVI or HPV DNA testing and eliminate colposcopy may offer attractive alternatives to cytology-based screening programs in low-resource settings.
JAMA The Journal of the American Medical Association 07/2001; 285(24):3107-15. · 29.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: We developed a mathematical simulation model to anticipate outcomes from an upcoming trial of targeted, preemptive cytomegalovirus (CMV) therapy in high-risk, human immunodeficiency virus (HIV)-infected patients identified by means of CMV polymerase chain reaction screening. We estimated the costs and consequences of CMV prophylaxis in patients with CD4(+) counts < or =100 cells/microL under various assumptions regarding disease progression, complication rates, drug effects, and costs. Without CMV preemptive therapy, lifetime costs average $44,600 with expected duration of survival of 19.16 quality-adjusted life-months and 213 CMV cases per 1000 patients. Targeted preemptive therapy with orally administered valganciclovir increases costs and duration of survival to $46,900 and 19.63 quality-adjusted life-months, respectively. CMV cases decrease to 174 per 1000 patients. The cost per quality-adjusted life-year gained is $59,000. This result compares favorably with other strategies in end-stage HIV disease but hinges on valganciclovir cost and efficacy assumptions and the absence of minimally effective salvage antiretroviral therapy for HIV. The upcoming trial should resolve the clinical uncertainty surrounding some of these assumptions.
[show abstract][hide abstract] ABSTRACT: Combination antiretroviral therapy with a combination of three or more drugs has become the standard of care for patients with human immunodeficiency virus (HIV) infection in the United States. We estimated the clinical benefits and cost effectiveness of three-drug antiretroviral regimens.
We developed a mathematical simulation model of HIV disease, using the CD4 cell count and HIV RNA level as predictors of the progression of disease. Outcome measures included life expectancy, life expectancy adjusted for the quality of life, lifetime direct medical costs, and cost effectiveness in dollars per quality-adjusted year of life gained. Clinical data were derived from major clinical trials, including the AIDS Clinical Trials Group 320 Study. Data on costs were based on the national AIDS Cost and Services Utilization Survey, with drug costs obtained from the Red Book.
For patients similar to those in the AIDS Clinical Trials Group 320 Study (mean CD4 cell count, 87 per cubic millimeter), life expectancy adjusted for the quality of life increased from 1.53 to 2.91 years, and per-person lifetime costs increased from $45,460 to $77,300 with three-drug therapy as compared with no therapy. The incremental cost per quality-adjusted year of life gained, as compared with no therapy, was $23,000. On the basis of additional data from other major studies, the cost-effectiveness ratio for three-drug therapy ranged from $13,000 to $23,000 per quality-adjusted year of life gained. The initial CD4 cell count and drug costs were the most important determinants of costs, clinical benefits, and cost effectiveness.
Treatment of HIV infection with a combination of three antiretroviral drugs is a cost-effective use of resources.
New England Journal of Medicine 04/2001; 344(11):824-31. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Genotypic sequencing for drug-resistant strains of HIV can guide the choice of antiretroviral therapy.
To assess the cost-effectiveness of genotypic resistance testing for patients acquiring drug resistance through failed treatment (secondary resistance) and those infected with resistant virus (primary resistance).
Cost-effectiveness analysis with an HIV simulation model incorporating CD4 cell count and HIV RNA level as predictors of disease progression.
Published randomized trials and data from the Multicenter AIDS Cohort Study, the national AIDS Cost and Services Utilization Survey, the Red Book, and an institutional cost-accounting system.
HIV-infected patients in the United States with baseline CD4 counts of 0.250 x 10(9) cells/L.
Genotypic resistance testing and clinical judgment, compared with clinical judgment alone, in two contexts: after initial treatment failure (secondary resistance testing) and before initiation of antiretroviral therapy (primary resistance testing).
Life expectancy, quality-adjusted life expectancy, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) gained.
Secondary resistance testing increased life expectancy by 3 months, at a cost of $17 900 per QALY gained. The cost-effectiveness of primary resistance testing was $22 300 per QALY gained with a 20% prevalence of primary resistance but increased to $69 000 per QALY gained with 4% prevalence.
The cost-effectiveness ratio for secondary resistance testing remained under $25 000 per QALY gained, even when effectiveness and cost of testing and antiretroviral therapy, quality-of-life weights, and discount rate were varied.
Genotypic antiretroviral resistance testing following antiretroviral failure is cost-effective. Primary resistance testing also seems to be reasonably cost-effective and will become more so as the prevalence of primary resistance increases.
Annals of internal medicine 04/2001; 134(6):440-50. · 13.98 Impact Factor