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.

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.

[Reduction in malaria case-fatality rate after implementation of an emergency plan for improved case management in the Bittou health district, Burkina Faso]. / Réduction de la létalité du paludisme après la mise en œuvre d'un plan d'urgence pour l'amélioration de la prise en charge des cas dans le district sanitaire de Bittou, Burkina Faso.

Objective: To observe the evolution in malaria case-fatality rate among children under 5 years of age receiving care at the Bittou district hospital (CMA) after an improvement of the care practices. The management team implemented an emergency plan in 2016 with 5 components: i) health facilities staff sensitization to enable rapid referral of severe malaria cases to CMA; ii) reorganization of CMA paediatric emergencies to make a physician as the mainpoint of contact; iii) ensuring availability of supplies for severe malaria case management, including the availability of blood; iv) daily medical check-ups of hospitalized patients; v) reinforcement of clinical staff skills at all peripheral health facilities. At the same time were introduced i) free care for children under 5 years; ii) municipality involvement to finance ambulance fuel for the referrals of patients; iii) free blood collection in professional schools and soldiers; iv) a free telephone line between the health structures; v) presence of 5 medical doctors at the CMA. Material and methods: Analysis of data collected from the statistical yearbooks of the Ministry of Health of Burkina Faso from 2014 to 2021. Results: The malaria case-fatality rate (CFR) in under-five in the Bittou health district (1.39% and 1.52% in 2014 and 2015) was higher than the average for all districts in this region (1.08%). After implementation of the emergency plan, the malaria CFR in Bittou declined to 0% in 2016 and 2017, 0.2% in 2018, 0% in 2019, 0.07% in 2020 and 0.05% in 2021. The same trend was observed at the CMA level with 2.94% and 2.59% in 2014 and 2015, 0% in 2016 and 2017, 0.38% in 2018, 0% in 2019, then 0.17% and 0.47% in 2020 and 2021. Conclusion: Malaria control remains a challenge in Burkina Faso. However, the improved malaria CFRs observed in Bittou show that effective involvement of health district teams could potentially contribute to substantial reductions in malaria case-fatality risk.

Continuous spread of HIV-1 subtypes D and CRF01_AE in France from 2003 to 2009.

Among 61 and 35 patients who were infected in France by viruses of the rare clades D and CRF01_AE, respectively, approximately half of them originated from areas where HIV-1 is endemic, but the data showed that both clades have spread in the French indigenous population, particularly in men having sex with men (MSM).

Difficulties of Identifying the Early HIV Antibody Seroconversion Period Depending on the Confirmatory Assay.

BACKGROUND: Identification of HIV infection at the early stage is valuable for patient management, for prevention, and for research purposes. In practice, identification of a recent HIV infection at diagnosis proves challenging after HIV antibody seroconversion but can be suspected using Western blots (WBs) or immunoblots (IBs) as confirmatory assays. METHODS: Five commercially available confirmatory assays were compared using 43 samples from recently infected individuals. This included 2 WBs (New LAV Blot I, Biorad, and HIV Blot 2.2, MP Biomedicals), 2 IBs (INNO-LIA HIV I/II, Fujirebio, and RecomLine HIV-1 & HIV-2, Mikrogen Diagnostik), and 1 immunochromatographic single-use assay (Geenius HIV1/2 supplemental assay, Biorad). RESULTS: Following the manufacturer's recommendations for interpretation, the 2 WBs led to indeterminate results for 30% and 42% of the samples, suggesting recent infection, compared with 2%-7% for the 3 other assays. When interpreted based on the Fiebig classification, concordant stages were observed in 42% of samples, and only 49% were classified as early seroconversion by all 5 assays. For the remaining specimens, the distinction with chronic infection was highly variable depending on the assay (5%-100%). CONCLUSIONS: Clinical laboratories must consider this variability, which must be kept in mind both for initial diagnosis and for multicenter studies for which inclusion criteria refer to serological profiles by confirmatory assays.

A national cross-sectional study among drug-users in France: epidemiology of HCV and highlight on practical and statistical aspects of the design.

BACKGROUND: Epidemiology of HCV infection among drug users (DUs) has been widely studied. Prevalence and sociobehavioural data among DUs are therefore available in most countries but no study has taken into account in the sampling weights one important aspect of the way of life of DUs, namely that they can use one or more specialized services during the study period. In 2004-2005, we conducted a national seroepidemiologic survey of DUs, based on a random sampling design using the Generalised Weight Share Method (GWSM) and on blood testing. METHODS: A cross-sectional multicenter survey was done among DUs having injected or snorted drugs at least once in their life. We conducted a two stage random survey of DUs selected to represent the diversity of drug use. The fact that DUs can use more than one structure during the study period has an impact on their inclusion probabilities. To calculate a correct sampling weight, we used the GWSM. A sociobehavioral questionnaire was administered by interviewers. Selected DUs were asked to self-collect a fingerprick blood sample on blotting paper. RESULTS: Of all DUs selected, 1462 (75%) accepted to participate. HCV seroprevalence was 59.8% [95% CI: 50.7-68.3]. Of DUs under 30 years, 28% were HCV seropositive. Of HCV-infected DUs, 27% were unaware of their status. In the month prior to interview, 13% of DUs shared a syringe, 38% other injection parapharnelia and 81% shared a crack pipe. In multivariate analysis, factors independently associated with HCV seropositivity were age over 30, HIV seropositivity, having ever injected drugs, opiate substitution treatment (OST), crack use, and precarious housing. CONCLUSION: This is the first time that blood testing combined to GWSM is applied to a DUs population, which improve the estimate of HCV prevalence. HCV seroprevalence is high, indeed by the youngest DUs. And a large proportion of DUs are not aware of their status. Our multivariate analysis identifies risk factors such as crack consumption and unstable housing.

Prevalence of HIV-2 and HIV-1 group O infections among new HIV diagnoses in France: 2003-2006.

French national surveillance of new HIV diagnoses included the collection of dried serum spots to identify HIV serotypes. Between January 2003 and June 2006, 10,184 new diagnoses were reported. The proportions of HIV-2 and HIV-1 group O infections were 1.8 and 0.1%, respectively. Most of these cases occurred in patients infected through heterosexual contact and originated from the corresponding endemic areas. Three cases of HIV-2 infections were reported in non-African men having sex with men.

HIV surveillance combining an assay for identification of very recent infection and phylogenetic analyses on dried spots.

BACKGROUND: Transmitted/founder viruses isolated at the early stage of infection are indicators of the variants that are spreading within a population. The French reporting system for new HIV diagnoses is linked to a virological surveillance using dried serum spots. METHODS: We combined an immunoassay for very recent infection (less than 31 days) to a phylogenetic analysis of transmitted/founder viruses and sociodemographic information to analyze the dynamics of the HIV-1 epidemic during a 3-year period. Bayesian coalescent-based methods were used to explore the temporal and spatial dynamics of the identified clusters. RESULTS: Of 17 010 dried serum spots collected, 549 very recent infections were identified for which both env sequences and sociodemographic data were available. Non-B transmitted/founder viruses were found in 196 cases (35.7%), belonging to six subtypes and seven circulating recombinant forms. Forty-three dyads/clusters were identified (range 2-11 cases), including 107 individuals (19.5%), mainly MSM. The largest cluster involved MSM infected by a CRF02_AG variant. Reconstruction of viral migrations across time suggests that Paris was the major hub of dissemination. CONCLUSION: The study shows the feasibility of the surveillance of the HIV epidemic using this methodology. The observation of actively growing spatiotemporal clusters allows identification of specific networks that may be targets for intervention.

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).

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 (< or =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. STUDY DESIGN AND METHODS: Of the 1027 donations found to be HIV-1-positive between 1992 and 2006, a total of 459 could be retrospectively tested with the EIA-RI. Multivariate analysis was performed to determine the donor characteristics associated with recent infection. Incidence rates and residual risk obtained with the EIA-RI were compared to classical cohort estimates derived from repeat donor histories. RESULTS: Of the 459 HIV-1-positive donors studied, 105 (22.9%; 95% confidence interval [CI], 19.2-27.0) were identified as recently infected. Factors independently associated with recent infection were repeat donor status (adjusted odds ratio [AOR], 4.0; 95% CI, 2.4-6.9) and non-B subtypes (AOR, 2.0; 95% CI, 1.2-3.6). Incidence decreased from 4.3 (95% CI, 1.9-9.4) in 1992 through 1994 to 1.3 (95% CI, 0.6-2.8) per 10(5) in 2004 through 2006 in first-time donors and from 3.2 (95% CI, 2.0-5.0) to 0.8 (95% CI, 0.4-1.4) per 10(5) in repeat donors. Incidence and residual risk estimates were similar to those obtained with the classical cohort method. CONCLUSION: This study suggests that the EIA-RI can be used to estimate HIV-1 incidence in a population with low HIV incidence. The estimated HIV-1 incidence in the blood donor population confirms the extremely low risk (1 in 3,350,000 donations) of HIV-infected blood donations entering the blood supply in France.

Human immunodeficiency virus serotyping on dried serum spots as a screening tool for the surveillance of the AIDS epidemic.

Many studies have demonstrated the utility of the dried blood spot (DBS) or dried plasma/serum spot (DSS) method for serological and molecular diagnosis of HIV infection. Here, we report on the description of a serotyping assay performed on DSS, and its application to a national surveillance program of HIV variants. We combined serotyping assays that we developed previously to discriminate between HIV-1 and HIV-2, between HIV-1 group O and HIV-1 group M, and between B and non-B subtypes of HIV-1 group M. The assays are based on antibody binding to either the immunodominant epitope of gp41 or the V3 domain of gp120 of these various types, groups and subtypes. Therefore, a unique enzyme-linked immunosorbent assay (ELISA) format applied to serum eluted from DSS allowed the simultaneous discrimination between infections caused by HIV-1 B, HIV-1 non-B, HIV-1 group O, and HIV-2. Together, this serotyping assay and an immunoassay for recent infection were used for a virological surveillance linked to the anonymous mandatory notification of HIV infection in France. The preliminary results of this virological surveillance allowed us to obtain estimates of the prevalence of the rare variants HIV-2 and HIV-1 group O. It also allowed identification of the two first cases of M/O dual infections reported outside the endemic group O region of the western part of equatorial Africa, and showed that non-B subtypes circulate widely in France, almost 50% of new HIV diagnoses in 2003 being due to these variants.