RESUMO
A case, in which the clinical suspicion of perinatal HIV transmission of a newly diagnosed 17-year-old woman was supported by the phylogenetic analyses of pol sequences obtained for routine resistance testing and further substantiated by analyses of gag and env, is described.
Assuntos
Genes Virais/genética , Infecções por HIV/transmissão , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas , Adolescente , Sequência de Bases , Feminino , Infecções por HIV/virologia , Humanos , Dados de Sequência Molecular , Filogenia , GravidezRESUMO
A molecular epidemiologic study of HIV-1 in Greenland showed distinct transmission clusters correlated with demographic and behavioral data. Resistance mutations were found in a majority of the pol sequences. The objective of the present study was to estimate prevalence of drug resistance in Greenland and identify transmission chains by comparing resistance data with phylogeny and treatment history. Of 60 untreated patients, 15 (25%) had primary resistance mutations. The most prevalent mutations were T69D/N (15%), K70R (15%), and M184V (10%). Four possible transmission chains were identified based on phylogeny and mutation profiles. The clusters consisted of treated and untreated patients and showed the same mutation profiles in both resistance and nonresistance positions. Prevalence of transmitted drug resistance in Greenland (25%) is higher than in Denmark where only 3% transmission was observed. Suboptimal use of nucleoside reverse transcriptase inhibitor (NRTI) in Greenland was reflected in the high prevalence of NRTI-related resistance in the patients. A combination of phylogeny and genotypic resistance tests enabled us to study the number of transmissions and how the virus was transmitted. Resistance mutations detected in untreated patients were backed up by the treatment history of index patients in the possible transmission chains and indicated that these drug-resistant variants were in fact transmitted and had not emerged due to unregistered drug intake.
Assuntos
Farmacorresistência Viral Múltipla , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , Estudos de Coortes , Feminino , Genes pol/genética , Groenlândia/epidemiologia , Humanos , Masculino , Filogenia , PrevalênciaRESUMO
A multi-drug-resistant, non-compliant HIV-1 patient was treated successfully with a combination of the drugs darunavir and etravirine for more than 8 months. The patient experienced an immunoreconstitution syndrome due to improved compliance. Examining previous resistance tests for this type of patient is valuable when assigning new medication.
Assuntos
Farmacorresistência Viral Múltipla , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Darunavir , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Testes de Sensibilidade Microbiana , Nitrilas , Cooperação do Paciente , Piridazinas/farmacologia , Piridazinas/uso terapêutico , Pirimidinas , Inibidores da Transcriptase Reversa/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Replicação Viral/efeitos dos fármacosRESUMO
Introduction of HIV-1 into a population may not always give rise to a subsequent epidemic. Greenland is an isolated and sparsely populated island in The Danish Kingdom. We aimed to estimate the number of introductions of HIV-1 into Greenland, the number of subsequent epidemics, and the countries from which the virus was introduced. Phylogenetic analyses were performed on three regions of HIV-1 (gag, pol, and env) in samples from 70 Greenlandic patients. Furthermore, we included gene sequences from contemporary Danish HIV-1-infected patients and sequences from the Los Alamos HIV Sequence Database. All Greenlandic sequences were subtype B except one sequence found to be a recombinant (probably CRF13). Sequence clusters in the phylogenetic trees indicated that there had been at least nine introductions of HIV-1 into Greenland. One cluster, supported by bootstrap values of 81, 76, and 96% for gag, pol, and env, corresponding to one introduction, contained 53 (76%) of the Greenland patients. The patients in the cluster differed from other Greenlandic patients in epidemiological parameters. Two distinct subgroups within the main cluster were concentrated around the two largest Greenlandic towns. Although HIV-1 has been introduced into Greenland at least nine times, only one introduction gave rise to an epidemic. The phylogeny did not indicate from where the main Greenland cluster had been introduced as no database sequence from outside Greenland was genetically close to this cluster. The large diversity between the main Greenland cluster and the rest of the sequences is most likely due to a founder effect.