Quantifying the risks and benefits of efavirenz use in HIV-infected women of childbearing age in the USA.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cost-effectiveness analysis of alternative first-trimester pregnancy termination strategies in Mexico City.

OBJECTIVE: To assess the comparative health and economic outcomes associated with three alternative first-trimester abortion techniques in Mexico City and to examine the policy implications of increasing access to safe abortion modalities within a restrictive setting. DESIGN: Cost-effectiveness analysis. SETTING: Mexico City. POPULATION: Reproductive-aged women with unintended pregnancy seeking first-trimester abortion. METHODS: Synthesising the best available data, a computer-based model simulates induced abortion and its potential complications and is used to assess the cost-effectiveness of alternative safe modalities for first-trimester pregnancy termination: (1) hospital-based dilatation and curettage (D&C), (2) hospital-based manual vacuum aspiration (MVA), (3) clinic-based MVA and (4) medical abortion using vaginal misoprostol. MAIN OUTCOME MEASURES: Number of complications, lifetime costs, life expectancy, quality-adjusted life expectancy. RESULTS: In comparison to the magnitude of health gains associated with all safe abortion modalities, the relative differences between strategies were more pronounced in terms of their economic costs. Assuming all options were equally available, clinic-based MVA was the least costly and most effective. Medical abortion with misoprostol provided comparable benefits to D&C, but cost substantially less. Enhanced access to safe abortion was always more influential than shifting between safe abortion modalities. CONCLUSIONS: This study demonstrates that the provision of safe abortion is cost-effective and will result in reduced complications, decreased mortality and substantial cost savings compared with unsafe abortion. In Mexico City, shifting from a practice of hospital-based D&C to clinic-based MVA and enhancing access to medical abortion will have the best chance to minimise abortion-related morbidity and mortality.

Health and economic impact of HPV 16 and 18 vaccination and cervical cancer screening in India.

Cervical cancer is a leading cause of cancer death among women in low-income countries, with approximately 25% of cases worldwide occurring in India. We estimated the potential health and economic impact of different cervical cancer prevention strategies. After empirically calibrating a cervical cancer model to country-specific epidemiologic data, we projected cancer incidence, life expectancy, and lifetime costs (I$2005), and calculated incremental cost-effectiveness ratios (I$/YLS) for the following strategies: pre-adolescent vaccination of girls before age 12, screening of women over age 30, and combined vaccination and screening. Screening differed by test (cytology, visual inspection, HPV DNA testing), number of clinical visits (1, 2 or 3), frequency (1 x , 2 x , 3 x per lifetime), and age range (35-45). Vaccine efficacy, coverage, and costs were varied in sensitivity analyses. Assuming 70% coverage, mean reduction in lifetime cancer risk was 44% (range, 28-57%) with HPV 16,18 vaccination alone, and 21-33% with screening three times per lifetime. Combining vaccination and screening three times per lifetime provided a mean reduction of 56% (vaccination plus 3-visit conventional cytology) to 63% (vaccination plus 2-visit HPV DNA testing). At a cost per vaccinated girl of I$10 (per dose cost of $2), pre-adolescent vaccination followed by screening three times per lifetime using either VIA or HPV DNA testing, would be considered cost-effective using the country's per capita gross domestic product (I$3452) as a threshold. In India, if high coverage of pre-adolescent girls with a low-cost HPV vaccine that provides long-term protection is achievable, vaccination followed by screening three times per lifetime is expected to reduce cancer deaths by half, and be cost-effective.

The cost-effectiveness of elective Cesarean delivery for HIV-infected women with detectable HIV RNA during pregnancy.

OBJECTIVES: To determine the net health consequences, costs, and cost-effectiveness of alternative delivery strategies for HIV-infected pregnant women with detectable HIV RNA in the USA. DESIGN: Cost-effectiveness analysis using a probabilistic decision model. METHODS: The model compared two strategies: elective Cesarean section and vaginal delivery. Data for HIV transmission rate, maternal death rate, health-related quality of life and costs were obtained from the literature, national databases, and a tertiary hospital's cost accounting system. Model outcomes included total lifetime costs, quality-adjusted life expectancy, maternal death rate, HIV transmission rate, and incremental cost-effectiveness ratios. RESULTS: Elective Cesarean section resulted in a vertical HIV transmission rate of 34.9 per 1000 births compared with 62.3 per 1000 births for vaginal delivery. Elective Cesarean section was more effective (38.7 quality adjusted life years per mother and child pair) and less costly ($10600 per delivery) than trial of labor (38.2 combined quality adjusted life years at a cost of $14500 per delivery). However, elective Cesarean section increased maternal mortality by 2.4 deaths per 100000 deliveries. The results were consistent over a wide range of the variables, but were sensitive to the risk of HIV transmission with vaginal delivery and the relative risk of HIV transmission with elective Cesarean section. CONCLUSIONS: In pregnant HIV-infected women with detectable HIV RNA, elective Cesarean section would reduce total costs and increase overall quality-adjusted life expectancy for the mother-child pair, albeit at a slight loss of quality adjusted life expectancy to the mother.

Prevention of human immunodeficiency virus-related opportunistic infections in France: a cost-effectiveness analysis.

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.

Cost effectiveness of human papillomavirus testing to augment cervical cancer screening in women infected with the human immunodeficiency virus.

PURPOSE: 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). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cost-effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men.

PURPOSE: Homosexual and bisexual men are at an increased risk for human papillomavirus-induced squamous intraepithelial lesions and cancer of the anus. Our objective was to estimate the cost-effectiveness of screening for anal squamous intraepithelial lesions in these high-risk patients. SUBJECTS AND METHODS: A Markov model was developed to evaluate alternative screening strategies using anal cytology in a hypothetical cohort of homosexual and bisexual men. Data were obtained from prospective cohort studies, national databases, Medicare reimbursement rates, and the published literature. Model outcomes included life expectancy, quality-adjusted life expectancy, total lifetime costs, and incremental cost-effectiveness ratios. RESULTS: The undiscounted life expectancy gain associated with anal cytology screening every 3 years was 5.5 months. Compared with no screening, screening every 3 years increased the discounted quality-adjusted life expectancy by 1.8 months and cost $7,000 per quality-adjusted life year (QALY) gained. Screening every 2 years cost $15,100 per QALY gained compared with screening every 3 years. Annual screening provided incremental benefits of less than 0.5 quality-adjusted months and had an incremental cost of $34,800 per QALY gained. Screening every 6 months provided little additional benefit (i.e, 5 days) over that of annual screening and had an incremental cost of $143,500 per QALY gained. CONCLUSION: In homosexual and bisexual men, screening every 2 or 3 years for anal squamous intraepithelial lesions with anal cytology would provide life-expectancy benefits comparable with other accepted preventive health measures, and would be cost-effective.

Cytomegalovirus as a primary pulmonary pathogen in AIDS.

In patients with AIDS, isolation of cytomegalovirus (CMV) from respiratory secretions is common. It is often found with other pathogens, which has led to debate regarding its role as a primary pulmonary pathogen. A retrospective investigation of patients with AIDS and CMV as a sole pulmonary isolate was performed in an attempt to describe their clinical presentation and course. All patients admitted to the hospital with pneumonia and with BAL or transbronchial biopsy (TBB) specimen positive for CMV between 1991 and 1994 were identified through a review of inpatient records. Inclusion criteria included positive CMV cultures from BAL, cytomegalic inclusion bodies from BAL or TBB, and thorough documentation of the absence of other pulmonary pathogens. Nine patients met the inclusion criteria for CMV pneumonitis. Seven were male and two were female, ages 26 to 44 years, and all had a history of opportunistic infections. Typical clinical presentation was characterized by increased respiratory rate, hypoxemia, and diffuse interstitial infiltrates. The mean CD4 count was 29.6 (+/- 22) cells per cubic millimeter, mean lactate dehydrogenase level was 414 (+/- 301) IU/L, and in seven patients in whom CMV antigen was measured it was greater than 50 positive cells per 200,000 WBCs. Three untreated patients died of respiratory failure and three had autopsy confirmation of CMV pneumonia. Five patients were treated with anti-CMV therapy for at least 2 weeks, and all demonstrated improvement in symptoms, oxygen saturation, and chest radiograph. At 3 months follow-up, all five patients were asymptomatic with no pulmonary symptoms. At 6 months follow-up, three of the five patients remained asymptomatic; the other two died of other opportunistic infections. In at least these nine patients, CMV represented a primary pulmonary pathogen. Patients who were treated responded quickly and were able to be discharged home from the hospital with marked improvement in their symptoms. We recommend that clinicians consider this diagnosis in the proper setting and consider treatment with anti-CMV therapy.

Incidence of primary opportunistic infections in two human immunodeficiency virus-infected French clinical cohorts.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cost-utility analyses of clinical preventive services: published ratios, 1976-1997.

BACKGROUND: Cost-effectiveness analyses of clinical preventive services are a potential means to aid public health resource allocation. Cost-utility analysis (CUA) is a specific form of cost-effectiveness analysis where results are expressed in terms of cost per quality-adjusted life year (QALY) gained. To increase the transparency and comparability of CUAs, standardization of methods has been recommended. OBJECTIVES: The purposes of this study were as follows: (1) identify published articles with original CUAs of primary and secondary clinical preventive services, (2) summarize the ratios found in these analyses, (3) identify articles employing comparable methods, and (4) explore analytic methods employed over time. METHODS: As part of a larger study we conducted a comprehensive search of published CUAs in the area of clinical preventive services and systematically collected data on the results of the analyses and analytic methods employed. Cost-effectiveness ratios were standardized and organized into a table. RESULTS: We found 50 CUAs pertaining to clinical preventive services (primary, n=22, 44%; and secondary, n=28, 56%) and 174 cost-effectiveness ratios. These ratios ranged from cost-savings up to $27,000,000/QALY, with a median of $14,000/QALY. Only three (6%) of the CUAs met minimum reference case requirements. There was no apparent improvement of methods over time. CONCLUSIONS: Immunizations and chemoprophylaxis have the most favorable cost-effectiveness ratios, and preventive services are more cost-effective when targeted at high-risk populations. However, there is wide variation in the methods used in these analyses. This study allows us to define where improvements in methodologic rigor need to occur, provides a base-line for future audits, and highlights disease areas in clinical preventive services that have been omitted or underevaluated.

Cost-effectiveness analysis: an introductory guide for clinicians.

UNLABELLED: Economic analyses are becoming increasingly prevalent in the obstetrics and gynecology literature, and it is essential that clinicians have a basic comprehension of this research methodology. The purpose of this article is to provide an introduction to economic analysis, in particular cost-effectiveness analysis, and to summarize the basic principles and recently proposed standards for studies using these analytic methods. The fundamental principle of economic analysis is that choices will have to be made between alternative use of resources because there are not unlimited resources to provide all the medical care possible to each individual. These analyses can illustrate the tradeoffs involved in choosing among a variety of clinical interventions to improve health care, and ultimately inform decision making. With a basic understanding of the key concepts of economic analyses, clinicians and health service researchers will be better prepared to critically review these analyses and incorporate them into daily practice. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to provide an introduction to economic analysis and to summarize the various types of economic analyses, to understand the principle assumption of each analysis and their limitations and to be aware of the various principles of conducting cost-effective analyses.

A Monte Carlo simulation of advanced HIV disease: application to prevention of CMV infection.

BACKGROUND: Disagreement exists among decision makers regarding the allocation of limited HIV patient care resources and, specifically, the comparative value of preventing opportunistic infections in late-stage disease. METHODS: A Monte Carlo simulation framework was used to evaluate a state-transition model of the natural history of HIV illness in patients with CD4 counts below 300/mm3 and to project the costs and consequences of alternative strategies for preventing AIDS-related complications. The authors describe the model and demonstrate how it may be employed to assess the cost-effectiveness of oral ganciclovir for prevention of cytomegalovirus (CMV) infection. RESULTS: Ganciclovir prophylaxis confers an estimated additional 0.7 quality-adjusted month of life at a net cost of $10,700, implying an incremental cost-effectiveness ratio of roughly $173,000 per quality-adjusted life year gained. Sensitivity analysis reveals that this baseline result is stable over a wide range of input data estimates, including quality of life and drug efficacy, but it is sensitive to CMV incidence and drug price assumptions. CONCLUSIONS: The Monte Carlo simulation framework offers decision makers a powerful and flexible tool for evaluating choices in the realm of chronic disease patient care. The authors have used it to assess HIV-related treatment options and continue to refine it to reflect advances in defining the pathogenesis and treatment of AIDS. Compared with alternative interventions, CMV prophylaxis does not appear to be a cost-effective use of scarce HIV clinical care funds. However, targeted prevention in patients identified to be at higher risk for CMV-related disease may warrant consideration.

Continuous peritoneal dialysis-associated peritonitis of nosocomial origin.

OBJECTIVE: To describe our experience with nosocomial continuous peritoneal dialysis (CPD)-associated peritonitis focusing on the incidence, possible risk factors, spectrum of organisms, and outcome. DESIGN: Retrospective review of the medical records of our CPD patients admitted to an acute-care hospital between November, 1993 and December, 1994. SETTING: University-associated acute-care hospitals in New Haven, Connecticut. PATIENTS: One hundred and eighty-eight patients maintained on CPD therapy and admitted to an acute-care hospital. RESULTS: Nineteen patients (5%) developing nosocomial peritonitis (NP) were identified from the 408 admissions occurring during the study period. Patients developing NP were older than the hospitalized CPD patients not developing NP (65.5 +/- 14.6 vs 58.4 +/- 14.7 years, p < 0.05). Comorbid diseases including diabetes, peripheral vascular disease, gastrointestinal disease, cardiovascular disease, and human immunodeficiency virus seropositivity were not more common in the patients developing NP. Patients developing NP were hospitalized significantly longer than the CPD patients not developing NP (39.5 +/- 46.5 days vs 12.7 +/- 12.4 days, p < 0.001). The mean serum albumin was lower in the NP patients than in the CPD patients not developing NP (2.35 +/- 0.52 g/dL vs 3.02 +/- 0.60 g/L, p < 0.001). Antecedent antibiotic use and performance of invasive procedures were noted in 89% and 68% of the patients developing NP, respectively. Staphylococcal species, enterococcal species, and gram-negative organisms accounted for 26%, 21%, and 53% of the episodes of NP, respectively. Furthermore, two strains of Enterococcus resistant to vancomycin were cultured. Eight patients developing NP expired, 8 patients continued CPD therapy, 2 patients transferred to hemodialysis, and one patient recovered renal function. CONCLUSION: We conclude that NP is uncommon. Increased age, increased length of hospital stay, and hypoalbuminemia may predispose patients to the development of NP. Further studies with case controls should help to clarify whether antecedent antibiotics or prior performance of invasive procedures predispose patients to the development of nosocomial peritonitis. The spectrum of organisms accounting for NP is different than the spectrum of organisms causing community-acquired CPD-associated peritonitis. Some of these organisms may be resistant to standard antibiotic therapies. Patients developing NP do poorly, with 42% expiring while being treated for NP.

Teaching care of terminally ill patients: a primary care perspective.

Currently there is a great interest in educating medical students in the care of patients with terminal illness. When medical students do encounter patients with terminal illness, it is often in the acute care setting. We have designed a workshop for fourth-year medical students who are working in general medical, family, or pediatrics practices as part of their month-long primary-care clerkship. The emphasis of this workshop is on the care of the terminally ill patient as a natural extension of the continuum of care offered by a primary-care physician. The workshop involves an interactive interview of a patient with a terminal illness by a group of four to eight students and the guidance of an experienced physician facilitator. Four themes are identified as central to the primary care of patients with terminal illness, and emphasis is placed on communication skills and the meaning of language to the dying patient.

Upregulation of CD26 expression in epithelial cells and stromal cells during wound-induced skin tumour formation.

We have previously described InvEE transgenic mice in which non-dividing, differentiating epidermal cells express oncogenically activated MAPK kinase 1 (MEK1). Skin wounding triggers tumour formation in InvEE mice via a mechanism that involves epidermal release of IL-1α and attraction of a pro-tumorigenic inflammatory infiltrate. To look for potential effects on the underlying connective tissue, we screened InvEE and wild-type epidermis for differential expression of cytokines and immune modulators. We identified a single protein, CD26 (dipeptidyl peptidase-4). CD26 serum levels were not increased in InvEE mice. In contrast, CD26 was upregulated in keratinocytes expressing mutant MEK1 and in the epithelial compartment of InvEE tumours, where it accumulated at cell-cell borders. CD26 expression was increased in dermal fibroblasts following skin wounding but was downregulated in tumour stroma. CD26 activity was stimulated by calcium-induced intercellular adhesion in keratinocytes, suggesting that the upregulation of CD26 in InvEE epidermis is due to expansion of the differentiated cell layers. IL-1α treatment of dermal fibroblasts stimulated CD26 activity, and therefore epidermal IL-1α release may contribute to the upregulation of CD26 expression in wounded dermis. Pharmacological blockade of CD26, via Sitagliptin, reduced growth of InvEE tumours, while combined inhibition of IL-1α and CD26 delayed tumour onset and reduced tumour incidence. Our results demonstrate that inappropriate activation of MEK1 in the epidermis leads to changes in dermal fibroblasts that, like the skin inflammatory infiltrate, contribute to tumour formation.

The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in a low-resource setting.

We assessed the cost-effectiveness of including boys vs girls alone in a pre-adolescent vaccination programme against human papillomavirus (HPV) types 16 and 18 in Brazil. Using demographic, epidemiological, and cancer data from Brazil, we developed a dynamic transmission model of HPV infection between males and females. Model-projected reductions in HPV incidence under different vaccination scenarios were applied to a stochastic model of cervical carcinogenesis to project lifetime costs and benefits. We assumed vaccination prevented HPV-16 and -18 infections in individuals not previously infected, and protection was lifelong. Coverage was varied from 0-90% in both genders, and cost per-vaccinated individual was varied from IUSD 25 to 400. At 90% coverage, vaccinating girls alone reduced cancer risk by 63%; including boys at this coverage level provided only 4% further cancer reduction. At a cost per-vaccinated individual of USD 50, vaccinating girls alone was

The long-term benefits of genotypic resistance testing in patients with extensive prior antiretroviral therapy: a model-based approach.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of opportunistic diseases on chronic mortality in HIV-infected adults in Côte d'Ivoire.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.