The concordance of the limiting antigen and the Bio-Rad avidity assays in persons from Estonia infected mainly with HIV-1 CRF06_cpx

BACKGROUND: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains. We evaluated the concordance of these assays in a population infected mainly with HIV-1 CRF06_cpx. MATERIAL/METHODS: Remnant serum samples (n = 288) collected from confirmed, newly-diagnosed HIV-positive persons from Estonia in 2013 were tested. Demographic and clinical data were extracted from clinical databases. LAg was performed according to the manufacturer’s protocol and BRAI testing was done using a validated protocol. Samples with LAg-pending or BRAI-invalid results were reclassified as recent if they were from persons with viral loads <1000 copies/mL or were reclassified as long-term if presenting with AIDS. RESULTS: In total 325 new HIV infections were diagnosed in 2013 in Estonia. Of those 276 persons were tested with both LAg and BRAI. Using assay results only, the recency rate was 44% and 70% by LAg and BRAI, respectively. The majority of samples (92%) recent by LAg were recent by BRAI. Similarly, 89% of samples long-term by BRAI were long-term by LAg. After clinical information was included in the analysis, the recency rate was 44% and 62% for LAg and BRAI, respectively. The majority of samples (86%) recent by LAg were recent by BRAI and 91% of long-term infections by BRAI were long-term by LAg. CONCLUSIONS: Comparison of LAg and BRAI results in this mostly CRF06_cpx-infected population showed good concordance for incidence classification. Our finding of a higher recency rate with BRAI in this population is likely related to the longer MDRI for this assay

HIV incidence in the Estonian population in 2013 determined using the HIV-1 limiting antigen avidity assay

Estonia has one the highest number of new HIV diagnoses in the European Union, mainly among injecting drug users and heterosexuals. Little is known of HIV incidence, which is crucial for limiting the epidemic. Using a recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV incidence in 2013. All individuals aged ≥18 years newly-diagnosed with HIV in Estonia January- December 2013, except blood donors and those undergoing antenatal screening, were included. Demographic and clinical data were obtained from the Estonian Health Board and the Estonian HIV-positive patient database. Serum samples were tested for recent infection using the LAg-avidity EIA assay. HIV incidence was estimated based on previously published methods. Of 69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age of 33 years (IQR: 28-42) and 65% male. Self-reported routes of HIV transmission were mostly heterosexual contact (n = 157, 53%) and injecting drug use (n = 62, 21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new infections in 2013 among the non-screened population. Incidence was highest (1.48%) among people who inject drugs. These high HIV incidence estimates in Estonia call for urgent action of renewed targeted public health promotion and HIV testing campaign

Implementation of a centralized pharmacovigilance system in academic pan‐European clinical trials : experience from EU‐Response and conect4children consortia

Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors