RESUMO
We investigated the prevalence of HIV-1-associated transmitted drug resistance (TDR) in Victoria from the time of first availability of highly active antiretroviral therapy. Drug resistance genotyping was performed on virus present in blood samples collected from individuals with serologically confirmed primary infection, between 1996 and 2007. The significance of any mutations detected was interpreted according to a standardised list of drug resistance mutations. The main outcomes measured were the prevalence by year of TDR to any antiretroviral drug class, the numbers of infected individuals with TDR involving multiple drug classes, and the resistance mutations implicated in all cases. There was an average annual prevalence of TDR of 16%, predominantly associated with nucleoside and non-nucleoside reverse transcriptase (RT) inhibitors and most commonly occurring at codons 41, 103 and 215 in the RT. The prevalence of thymidine-associated mutations remained high throughout the period of study. While mutations known to cause resistance to protease inhibitors were uncommon, they were present in several individuals infected with virus resistant to multiple drug classes. The prevalence of TDR in Victoria is similar to geographical locations outside Australia where HIV-specific drug treatment is widely available. Primary infection with drug resistant HIV is a future treatment issue for the individual patient and for the wider population at risk of infection. At this time TDR shows no sign of waning and our data support recent treatment guidelines recommending baseline testing for TDR before therapy is initiated.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Austrália/epidemiologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Feminino , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Masculino , PrevalênciaRESUMO
Resistance to the HIV fusion inhibitor enfuvirtide is associated with mutations in the first heptad repeat region of gp41, but little is known of their impact on replicative fitness in vivo. We followed seven patients undergoing salvage therapy that included enfuvirtide in order to document the temporal generation of genotypic and phenotypic resistance in parallel with replicative fitness. Resistance to enfuvirtide was not associated with decreased replicative fitness of HIV strains infecting these patients.
