Sylvie Deuffic-Burban

Routine HIV Screening in France: Clinical Impact and Cost-Effectiveness

Background In France, roughly 40,000 HIV-infected persons are unaware of their HIV infection. Although previous studies have evaluated the cost-effectiveness of routine HIV screening in the United States, differences in both the epidemiology of infection and HIV testing behaviors warrant a setting-specific analysis for France. Methods/Principal Findings We estimated the life expectancy (LE), cost and cost-effectiveness of alternative HIV screening strategies in the French general population and high-risk sub-populations using a computer model of HIV detection and treatment, coupled with French national clinical and economic data. We compared risk-factor-based HIV testing (“current practice”) to universal routine, voluntary HIV screening in adults aged 18–69. Screening frequencies ranged from once to annually. Input data included mean age (42 years), undiagnosed HIV prevalence (0.10%), annual HIV incidence (0.01%), test acceptance (79%), linkage to care (75%) and cost/test (€43). We performed sensitivity analyses on HIV prevalence and incidence, cost estimates, and the transmission benefits of ART. “Current practice” produced LEs of 242.82 quality-adjusted life months (QALM) among HIV-infected persons and 268.77 QALM in the general population. Adding a one-time HIV screen increased LE by 0.01 QALM in the general population and increased costs by €50/person, for a cost-effectiveness ratio (CER) of €57,400 per quality-adjusted life year (QALY). More frequent screening in the general population increased survival, costs and CERs. Among injection drug users (prevalence 6.17%; incidence 0.17%/year) and in French Guyana (prevalence 0.41%; incidence 0.35%/year), annual screening compared to every five years produced CERs of €51,200 and €46,500/QALY. Conclusions/Significance One-time routine HIV screening in France improves survival compared to “current practice” and compares favorably to other screening interventions recommended in Western Europe. In higher-risk groups, more frequent screening is economically justifiable.

Quantification of fibrosis progression in patients with chronic hepatitis C using a Markov model

The knowledge of fibrosis progression in chronic hepatitis C and the impact of new treatments on progression is limited by the number of available liver biopsies per patient. Moreover, liver biopsies identify a patients stage of fibrosis at a given point in time, but cannot quantify the time spent in that stage nor the date of transition to that stage. This paper assesses the potential of Markov modelling to overcome these difficulties. The data from interferon‐treated (n=185) and untreated patients (n=102) are analysed to illustrate the power of this technique.

Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study

BackgroundIn France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients.MethodsCross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions.Results1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing.ConclusionsUnder current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities.

Impact of viral eradication on mortality related to hepatitis C : A modeling approach in France

BACKGROUND/AIMS In France, two recent studies enabled modeling of the impact of viral eradication on HCV mortality. METHODS The French HCV population was simulated from infection to death using a computer-based model. We took into account the impact of alcohol, present screening and antiviral therapy to predict 2006--2025 HCV mortality and to assess the impact of viral eradication. RESULTS In 2006, the model estimated that among HCV-RNA+, 55% were F0-F1, 18% F2, 22% F3-F4 and 6% had liver complications. The mortality ratio was 11-fold higher in alcoholic patients 40-65 years old. Current therapy will save 14,400 (95% CI, 13,900-15,000) lives compared to absence of therapy. Sensitivity analyses did not change the main results. Contrary to guidelines, if patients F<2 were treated in the same proportions as those with F> or = 2,700 (95% CI, 700-750) lives would be saved. If screening were to reach 75% in 2010, 4 years earlier than model expectation, 950 (95% CI, 900-1000) lives would be saved. If a new molecule improving eradication for genotype 1/4 by 40% were to become available in 2010, 1500 (95% CI, 1400-1600) lives would be saved. CONCLUSIONS Current therapy is reducing HCV mortality. Therapeutic guidelines must take into account their impact on HCV mortality.

Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France.

Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)‐infected patients with normal alanine aminotransferase (N‐ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E‐ALT). This study was undertaken to predict the impact of pegylated interferon (IFN) and ribavirin on HCV‐related morbidity and mortality in patients with N‐ALT. A previous Markov model was adapted to separately simulate patients with N‐ALT (30%) and those with E‐ALT (70%). The model estimates fibrosis progression rates according to age, sex, and whether ALT levels are normal or elevated, assuming that patients with E‐ALT have a 2.6 times higher progression than those with N‐ALT. It takes into account improvement in HCV screening and treatment and competitive mortality. We assumed that N‐ALT patients were treated 80% less frequently between 2002 and 2004 and 70% less frequently from 2005 on, as obtained in real life from three multicentric cohorts (Hepatys, Adequation, Persee). Antiviral treatment of HCV‐infected populations might reduce 2008‐2025 HCV‐related morbidity and mortality by 34,200 cases of cirrhosis (36%, 33,000‐35,000), 22,400 complications (28%, 21,000‐23,000) and 17,500 deaths (25%, 17,000‐18,000), including 3000 cases of cirrhosis (22%, 2000‐5000), 1200 complications (15%, 1000‐1700), and 1000 deaths (14%, 900‐1300) in the N‐ALT population, despite a probability of receiving treatment that is three to five times less in this population. If N‐ALT patients are treated at the same proportions as those with E‐ALT, morbidity and mortality could be further reduced by 1400 cases of cirrhosis (13%, 1200‐2200), 600 complications (9%, 600‐1000), and 500 deaths (9%, 500‐800). Conclusion: Treatment of N‐ALT patients would decrease HCV morbidity and mortality. These patients should be considered candidates for treatment just as others are. (HEPATOLOGY 2009.)

Efficacy of new antiretroviral drugs in treatment-experienced HIV-infected patients: a systematic review and meta-analysis of recent randomized controlled trials.

We performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) to assess the overall efficacy of new antiretroviral drugs, as well as the factors associated with increased efficacy. We compared CD4 cell count increases associated with chemokine (C‐C motif) receptor 5 (CCR5) inhibitors or other new drugs, using indirect comparison.

Impact of hepatitis C triple therapy availability upon the number of patients to be treated and associated costs in France: a model-based analysis

Objective The combination of pegylated interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor (PI) has been approved in summer 2011 for the treatment of genotype 1 (G1) hepatitis C virus (HCV)-infected patients, with a substantially improved efficacy. The aim of this study was to estimate the number of G1 patients to be treated in France in 2012 and associated costs. Methods A published model of HCV and data on PEG-IFN sales were used to estimate patients needing treatment using three scenarios. (1) HCV screening rate unchanged versus 2010; proportion of treated F0–F1 patients unchanged, proportion of treated F2–F4 patients increased to the current proportion of treated F2–F4 G2/3 patients. (2) Scenario 1 but the proportion of treated F0–F1 patients increased to the current proportion of treated F0–F1 G2/3 patients. (3) Scenario 2 but a 5% increase in the HCV screening rate. To estimate cost, treatment duration was multiplied by drug unit cost. Probabilities corresponding to treatment duration were estimated based on liver fibrosis stage, treatment-naive or experienced status of the patient and virological response kinetics on treatment. Results Compared with the 5100 G1 patients treated in 2010, the number of G1 patients receiving treatment in 2012 would be 15 000 in scenario 1, 18 300 in scenario 2 and 19 400 in scenario 3, among whom 2.5–3.7% may receive PEG-IFN/RBV and 96.3–97.5% PEG-IFN/RBV+PI. Costs associated with this regimen use ranged from 497 to 638 million Euros. Conclusion These model-based estimates indicate that new anti-HCV treatments may result in a three- to fourfold increase in the number of G1 patients to be treated in France in 2012.

2014 French guidelines for hepatitis B and C screening: a combined targeted and mass testing strategy of chronic viruses namely HBV, HCV and HIV

Worldwide and, to a lesser extent, in France, a minority of individuals infected with hepatitis B (HBV) and C (HCV) is aware of its status. Given the current availability of highly effective anti‐HBV and anti‐HCV agents, the high rate of undiagnosed people, associated with individual and community prejudices (liver disease worsening, persistence of a hidden transmission reservoir and medicoeconomic burden of delayed care), is unacceptable.

Expected response to protease inhibitors of HIV-1 non-B subtype viruses according to resistance algorithms.

The expected effectiveness of protease inhibitors was assessed according to the Agence Nationale de Recherches sur le SIDA (ANRS), Rega and Stanford 2007 resistance algorithms in 93 and 87 antiretroviral therapy-naive patients, respectively, infected with B and non-B subtype viruses.Either B or non-B subtypes were considered fully susceptible to protease inhibitors, except to tipranavir/ritonavir, for which the 2007 ANRS algorithm scored non-B subtypes as naturally resistant when this algorithm was extended to these subtypes.

Costs and cost-effectiveness of different follow-up schedules for detection of occupational hepatitis C virus infection

Objective: The purpose of this study was to compare the costs and cost-effectiveness (C/E) of early hepatitis C virus (HCV) RNA testing (alternative-US recommendations) after occupational exposure to HCV with existing follow-up strategies: (1) French, anti-HCV antibodies and alanine transaminase (ALT) activity at months 1, 3 and 6; (2) European, monthly ALT activity for 4 months and anti-HCV antibodies at month 6; (3) and baseline-US, anti-HCV antibodies and ALT activity at month 6. Methods: A decision tree simulated each strategy for 7300 healthcare workers (HCWs) exposed to HCV each year in France, taking into account the impact of early diagnosis on the response to antiviral treatment and the deterioration of HCW quality of life after exposure. Results: For a HCV transmission risk of 0.5% after exposure, the French strategy led to the highest costs/person (€181.40) and the baseline-US strategy to the lowest (€126.60) (€178.50) for alternative-US). The shortest mean time to HCV infection diagnosis (1 month) and the lowest number of chronic hepatitis C (CHC) patients (1.9/7300 HCWs exposed) was obtained with the alternative-US strategy (vs 6 months and 7.9 CHC, respectively with baseline-US). Compared with the alternative-US, the French strategy was associated with higher costs and lower utilities, and the European with a higher incremental C/E ratio. Compared with the baseline-US strategy, the alternative-US strategy C/E ratio was €2020 per quality-adjusted life year saved. Conclusion: In HCWs exposed to HCV, a strategy based on early HCV RNA testing shortens the period during which the HCW’s wait for his HCV status, leads to lower risk of progression to CHC and is reasonably cost-effective.