Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes.
OBJECTIVE
To describe the prevalence of the L76V protease inhibitors resistance-associated mutation (PI-RAM) in relation with patients' characteristics and protease genotypic background in HIV-1 B- and "non-B"-infected patients.


METHODS
Frequency of the L76V mutation between 1998 and 2010 was surveyed in the laboratory database of 3 clinical centers. Major PI-RAMs were identified according to the IAS-USA list. Fisher's and Wilcoxon tests were used to compare variables.


RESULTS
Among the overall 29,643 sequences analyzed, the prevalence of L76V was 1.50%, while was 5.42% in PI-resistant viruses. Since 2008 the prevalence of L76V was higher in "non-B"-infected than in B-infected patients each year. Median time since diagnosis of HIV-1 infection and median time under antiretroviral-based regimen were both shorter in "non-B"- than in B-infected patients (8 vs 11 years, P<0.0001; and 7 vs 8 years, P = 0.004). In addition, "non-B"-infected patients had been pre-exposed to a lower number of PI (2 vs 3, P = 0.016). The L76V was also associated with a lower number of major PI-RAMs in "non-B" vs B samples (3 vs 4, P = 0.0001), and thus it was more frequent found as single major PI-RAM in "non-B" vs B subtype (10% vs 2%, P = 0.014).


CONCLUSIONS
We showed an impact of viral subtype on the selection of the L76V major PI-RAM with a higher prevalence in "non-B" subtypes observed since 2008. In addition, in "non-B"-infected patients this mutation appeared more rapidly and was associated with less PI-RAM.
Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Paris 7, PRES Sorbonne Paris Cité, EA4409, Paris, France. charlotte.charpentier@bch.aphp.fr
Charlotte
C
Charpentier
Sidonie
S
Lambert-Niclot
Claudia
C
Alteri
Alexandre
A
Storto
Philippe
P
Flandre
Valentina
V
Svicher
Carlo-Federico
CF
Perno
Françoise
F
Brun-Vézinet
Vincent
V
Calvez
Anne-Geneviève
AG
Marcelin
Francesca
F
Ceccherini-Silberstein
Diane
D
Descamps
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D016333:HIV Protease