Primary resistance to enfuvirtide (T20) in recently HIV-1 infected, antiretroviral-naive patients from the ANRS Aquitaine Cohort.
BACKGROUND
Transmission of HIV-1 variants with resistance to reverse transcriptase (RT) and protease inhibitors has been widely characterized in developed countries. However, no clear evidence of primary resistance to HIV-1 fusion inhibitors has been shown so far. We wished to investigate the possibility of genotypic resistance to enfuvirtide (T20) in a cohort of antiretroviral-naive, recently infected patients.


METHODS
We included patients from the Aquitaine Cohort with an estimated date of seroconversion in 2004 and 2005, a plasma sample obtained less than 18 months after seroconversion and no prior history of antiretroviral therapy. RT, protease and gp41 sequences were determined by direct population sequencing from plasma samples and drug resistance mutations were reported.


RESULTS
A total of 55 patients were included in the study. The overall prevalence of transmitted HIV-1 resistance was 20%. Two patients had viruses with resistance mutations to T20. The first case had an N42D mutation in the HR1 region of the gp41, along with transmitted resistance mutations in the protease (D30N, M361, N88D) and in the RT (M41L, L210W, T215D). The second case had a G36D HR1 mutation, with no evidence of other drug resistance mutations.


CONCLUSIONS
We have shown the first cases of primary resistance to T20 in recently infected patients in southwestern France. Epidemiological surveillance of the transmission of drug-resistant HIV-1 should include the resistance to T20.
Department de Virologie et Immunologie Biologique, CHU de Bordeaux, France.
Olivia
O
Peuchant
Sophie
S
Capdepont
Jean-Marie
JM
Ragnaud
Valérie
V
Aurillac-Lavignolle
Rodolphe
R
Thiébaut
Hervé
H
Fleury
Bernard
B
Masquelier
D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010446:Peptide Fragments / Q000494:pharmacology*; D010802:Phylogeny
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide; D054303:HIV Reverse Transcriptase; D016333:HIV Protease