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Abstract:

Background: Every day, around 7000 people still get infected with HIV worldwide. Antiretroviral (ARV) therapy reduced morbidity and mortality, and while early ART is expected to reduce incidence, transmission of HIV infection is still ongoing. Transmission investigations shed light on how to prevent HIV spread and on the origin of transmitted drug resistance (TDR). Clinical, socio-behavioral and therapy adherence factors influence the transmission of HIV and the efficacy of interventions. Objectives: The main goal is to construct a cohort to analyze the prevalence and characteristics of TDR in newly diagnosed HIV-1 patients and to describe and analyze risk factors associated with HIV-1 infection and transmission of drug resistance in Portugal. Methods: The BEST HOPE cohort includes patients at least 18 years old, with a new HIV diagnosis since September 2014 and a baseline drug resistance test. Data include clinical characteristics of the patients collected through a questionnaire and the HIV genomic sequence obtained from the drug resistance test. Additionally, patients from specific vulnerable groups - Men who have sex with Men (MSM) and Migrants - fill in a questionnaire concerning socio-behavioral factors associated with HIV infection. Patients are being recruited in 18 Portuguese hospitals, covering most regions of the country. Drug resistance testing with population-based Sanger sequencing of protease and partial reverse transcriptase. TDR mutations were defined according to the 2009 list of surveillance drug resistance mutations from the WHO. Nucleotide sequences were submitted to the Calibrated Population Resistance tool -HIV drug resistance database version 6.0 and the clinical impact of TDR was evaluated with HIVdb v7.0 and Rega v 9.1.0. Results: Until now, we have collected data from 248 HIV-positive patients, including 38 migrants and 101 MSM. The most common subtypes identified were B (42%) and G (17%). The incidence of subtype G decreased substantially when compared to the last study performed in Portugal (SPREAD) (29.4%). Conversely, the incidence of subtype A1 increased from 1.7% to 11%. Subtype A1 is circulating in Portuguese MSMs (18%), concordantly to what has been found in other European countries. The subtypes circulating in MSMs compared to migrants are very different, suggesting the existence of compartmentalized epidemics. Primary drug resistance (PDR) was detected in 13.7% of individuals. This value almost doubled compared to SPREAD, where 7.8% of patients were identified as carrying resistance associated mutations. Detected PDR to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) is worrying, with 5.2% of patients presenting high level resistance to Efavirenz (EFV) or Nevirapine (NVP) and 0,8% to Rilpivirine (RPV) at baseline. Primary drug resistance was found in 11.9% of MSMs and in 11.1% of migrants. Conclusion: Our study will provide an innovative molecular epidemiological perspective about the determinants of HIV transmission, with or without TDR. These results will be useful to inform Public Health entities for designing prevention policies. We will present preliminary results concerning the molecular epidemiology and characteristics of TDR in Portugal and in specific vulnerable groups.