Stéphane Le Vu

Population-based HIV-1 incidence in France, 2003–08: a modelling analysis

BACKGROUND Routine national incidence testing with enzyme immunoassay for recent HIV-1 infections (EIA-RI) has been done in France since January, 2003. From the reported number of HIV infections diagnosed as recent, and accounting for testing patterns and under-reporting, we aimed to estimate the incidence of HIV infection in France in 2003-08. METHODS We analysed reports from the French National Institute for Public Health Surveillance for patients who were newly diagnosed with HIV between January, 2003, and December, 2008. Missing data were imputed with multiple imputation. Patients were classified with non-recent or recent infection on the basis of an EIA-RI test, which was calibrated with serial measurements from HIV seroconverters from the French ANRS-PRIMO cohort. We used an adapted stratified extrapolation approach to calculate the number of new HIV infections in men who have sex with men (MSM), injecting drug users (IDUs), and heterosexual men and women by nationality. Population sizes were obtained from the national census and national behavioural studies. FINDINGS After accounting for under-reporting, there were 6480 (95% CI 6190-6780) new diagnoses of HIV infection in France in 2008. We estimate that there were 6940 (6200-7690) new HIV infections in 2008, suggesting an HIV incidence of 17 per 100 000 person-years. In 2008, there were 3550 (3040-4050) new infections in heterosexuals (incidence of 9 per 100 000 person-years), 3320 (2830-3810) in MSM (incidence of 1006 per 100 000 person-years), and 70 (0-190) in IDUs (incidence of 86 per 100 000 person-years). Overall HIV incidence decreased between 2003 and 2008 (p<0·0001), but remained comparatively high and stable in MSM. INTERPRETATION In France, HIV transmission disproportionately affects certain risk groups and seems to be out of control in the MSM population. Incidence should be tracked to monitor transmission dynamics in the various population risk groups and to help to target and assess prevention strategies. FUNDING French National Institute for Public Health Surveillance (InVS) and French National Agency for Research on AIDS and Viral Hepatitis (ANRS).

Monitoring the Dynamics of the HIV Epidemic Using Assays for Recent Infection and Serotyping among New HIV Diagnoses: Experience after 2 Years in France

BACKGROUND New tools to better monitor dynamics of human immunodeficiency virus (HIV) transmission are needed. METHODS National surveillance of newly HIV diagnoses included the collection of dried serum spots to identify both recent infections (<6 months) and HIV serotypes. Multivariate analyses were used to identify factors associated with recent infection and infection with non-B subtypes. RESULTS Between 2003 and March 2005, 7902 new HIV diagnoses were reported. The overall proportion of recent infections was 24.9% (95% confidence interval, 23.8%-26.0%) and was highest among men who have sex with men (MSM; 46%). Recent infection was associated with being an MSM, <30 years old, of French nationality, and living in Paris. Nearly half of newly HIV-1 diagnoses were with non-B subtypes. The highest proportion of non-B infections was reported among African heterosexual persons (81%), but important proportions were reported among French heterosexual persons (34%) and MSM (12%). Being infected by a non-B subtype was independently associated with being African, <30 years old, heterosexual, and living in Paris. The proportion of HIV-2 infection was 1.9%, and 11 cases of HIV-1 group O infection were identified, mainly among West Africans. CONCLUSIONS There is evidence of high levels of HIV transmission among MSM in France and transmission of non-B subtypes within the indigenous French population.

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.

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.

Biomarker-based HIV incidence in a community sample of men who have sex with men in Paris, France.

Background Population-based estimates of HIV incidence in France have revealed that men who have sex with men (MSM) are the most affected population and contribute to nearly half of new infections each year. We sought to estimate HIV incidence among sexually active MSM in Paris gay community social venues. Methodology/ Principal Findings A cross-sectional survey was conducted in 2009 in a sample of commercial venues such as bars, saunas and backrooms. We collected a behavioural questionnaire and blood sample. Specimens were tested for HIV infection and positive specimens then tested for recent infection by the enzyme immunoassay for recent HIV-1 infection (EIA-RI). We assessed the presence of antiretroviral therapy among infected individuals to rule out treated patients in the algorithm that determined recent infection. Biomarker-based cross-sectional incidence estimates were calculated. We enrolled 886 MSM participants among which 157 (18%) tested HIV positive. In positive individuals who knew they were infected, 75% of EIA-RI positive results were due to ART. Of 157 HIV positive specimens, 15 were deemed to be recently infected. The overall HIV incidence was estimated at 3.8% person-years(py) [95%CI: 1.5–6.2]. Although differences were not significant, incidence was estimated to be 3.5% py [0.1–6.1] in men having had a negative HIV test in previous year and 4.8% py [0.1–10.6] in men having had their last HIV test more than one year before the survey, or never tested. Incidence was estimated at 4.1% py [0–8.3] in men under 35 years and 2.5% py [0–5.4] in older men. Conclusions/ Significance This is the first community-based survey to estimate HIV incidence among MSM in France. It includes ART detection and reveals a high level of HIV transmission in sexually active individuals, despite a high uptake of HIV testing. These data call for effective prevention programs targeting MSM engaged in high-risk behaviours.

Late Diagnosis and Entry to Care after Diagnosis of Human Immunodeficiency Virus Infection: A Country Comparison

Background Testing for HIV infection and entry to care are the first steps in the continuum of care that benefit individual health and may reduce onward transmission of HIV. We determined the percentage of people with HIV who were diagnosed late and the percentage linked into care overall and by demographic and risk characteristics by country. Methods Data were analyzed from national HIV surveillance systems. Six countries, where available, provided data on two late diagnosis indicators (AIDS diagnosis within 3 months of HIV diagnosis, and AIDS diagnosis within 12 months before HIV diagnosis) and linkage to care (≥1 CD4 or viral load test result within 3 months of HIV diagnosis) for people diagnosed with HIV in 2009 or 2010 (most recent year data were available). Principal Findings The percentage of people presenting with late stage disease at HIV diagnosis varied by country, overall with a range from 28.7% (United States) to 8.8% (Canada), and by transmission categories. The percentage of people diagnosed with AIDS who had their initial HIV diagnosis within 12 months before AIDS diagnosis varied little among countries, except the percentages were somewhat lower in Spain and the United States. Overall, the majority of people diagnosed with HIV were linked to HIV care within 3 months of diagnosis (more than 70%), but varied by age and transmission category. Conclusions Differences in patterns of late presentation at HIV diagnosis among countries may reflect differences in screening practices by providers, public health agencies, and people with HIV. The percentage of people who received assessments of immune status and viral load within 3 months of diagnosis was generally high.

Human immunodeficiency virus type 1 incidence among blood donors in France, 1992 through 2006 : use of an immunoassay to identify recent infections

BACKGROUND: In France, blood donations found to be positive for the presence of human immunodeficiency virus type 1 (HIV‐1) are further tested to detect recent infections (≤180 days) using an enzyme immunoassay (EIA‐RI) developed in 2002. The characteristics of recently infected donors, estimates of HIV‐1 incidence, and the residual risk of transfusion‐transmitted HIV‐1 are presented, in both first‐time and repeat donors.

Performance of an immunoassay at detecting recent infection among reported HIV diagnoses.

Introduction:An enzyme immunoassay to detect recent HIV-1 infection (EIA-RI) of less than 6 months is routinely performed on diagnoses reported to the National HIV case surveillance in France. We assessed the performance of the EIA-RI infection on this country population scale by measuring its agreement with other indicators of time since infection that were obtained through clinical, biological or testing history recorded on the surveillance reporting form. Methods:We used data from the National HIV case surveillance from its debut in March 2003 to June 2007. Infection within 6 months was defined as a negative test reported within 6 months prior to diagnosis. We further ascertained this definition by adding information about of a symptomatic primary infection or biological evidence of recent seroconversion. Infection established for more than 6 months was defined when a positive test had occurred more than 6 months prior to the reported diagnosis. Results:Time since infection could be ascertained in 6782 of 15 331 (44.2%) HIV diagnoses. Assay sensitivity and specificity were 73.8 and 83.7%, respectively. Among the 1940 cases originating from Sub-Saharan Africa, sensitivity and specificity were 54.1 and 90.8%, respectively. Discussion:Assessment of the performance of the EIA-RI on a large and heterogeneous population revealed two major findings—significant discrepancies in timing from infection near the 180-day cutoff, and a performance that depends on the geographic origin of patients. This has implications for estimating the assay window period and in the perspective of incidence estimation from HIV case surveillance.

Characteristics of Patients Recently Infected with HIV-1 Non-B Subtypes in France: a Nested Study within the Mandatory Notification System for New HIV Diagnoses

ABSTRACT The presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. The French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415-bp env region, followed by phylogenetic analysis and search for transmission clusters. Two hundred thirty-three recent HIV-1 infections with non-B variants were identified. They involved 5 subtypes and 7 circulating recombinant forms (CRFs). Ninety-two cases (39.5%) were due to heterosexual transmissions, of which 39 occurred in patients born in France. Eighty-five cases (36.5%) were identified in men having sex with men (MSM). Forty-three recent non-B infections (18.5%) segregated into 14 clusters, MSM being involved in 11 of them. Clustered transmission events included 2 to 7 cases per cluster. The largest cluster involved MSM infected by a CRF02_AG variant. In conclusion, we found that the spread of non-B subtypes in France occurs in individuals of French origin and that MSM are particularly involved in this dynamic.

Undiagnosed HIV prevalence based on nontargeted screening in emergency departments.

To estimate the 2009–2010 undiagnosed HIV prevalence in the Paris metropolitan region, where half of Frances new HIV cases are diagnosed annually, we used a direct method based on a large sample of emergency department patients unaware of their HIV status. The overall expected prevalence was 0.09% (95% confidence interval 0.04–0.13). Undiagnosed infections were exclusively found in high-risk groups. This prevalence is below the 0.1% threshold suggested by regulatory authorities for implementing universal screening.