Molecular epidemiology and prevalence of drug resistance-associated mutations in newly diagnosed HIV-1 patients in Portugal

摘要

BACKGROUND: Drug resistance transmission in newly diagnosed, drug-naive HIV-1 infected individuals has been previously reported, with rates ranging from 5 to 27%. The aim of this study is to investigate the prevalence of resistance-associated mutations in drug-naive, newly diagnosed patients, as well as monitoring the diversity of HIV-1 strains circulating in Portugal. METHODS: One hundred eighty samples from newly diagnosed patients were prospectively collected during 2003, according to the distribution of HIV-1 infections in Portugal. Epidemiological, clinical and laboratory data was collected using a standardized form. Population sequencing was performed using an automated sequencer (ABI Prism 3100, Applied Biosystems) and a commercially available assay (ViroSeq HIV-1 Genotyping System, v2.0, Abbott). Stanford HIV Sequence Database was used for interpretation of resistance data; subtyping was performed using the REGA Subtyping Tool. When subtype was unassigned, further analysis was done using an alignment with reference sequences, and phylogenetic tools like Simplot and PHYLIP. Mutations listed by the International AIDS Society-USA were considered, except E44D and V118I. RESULTS: Patient population included 124 males (69%) and 56 females (31%), the median age being 35. Western Europe was the main region of origin (77.2%), followed by Africa (18.3%), South America (2.8%) and Asia (1.1%). The most common route of transmission was heterosexual contact (54.4%), followed by intravenous drug use (20%), homo/bisexual individuals (19.4%) and blood transfusion (0.6%). The commonest subtypes were B (41.7%) and G (29.4%), while other non-B subtypes rated 12.8% and recombinant forms represented 16.1% of the samples. Fourteen patients (7.78%) were identified as carrying resistance-associated mutations. Ten were resistant to drugs from one class, three to drugs from two classes and one to drugs from all three classes. No statistically significant associations were found between age, gender, route of transmission, subtype and resistance. CONCLUSIONS: The identification of newly diagnosed individuals carrying resistance-associated mutations confirms that drug resistance transmission is a public health problem in Portugal, with a possible impact on prevention, treatment and monitoring of HIV-1 infections.