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. 2013;8(1):e54381.
doi: 10.1371/journal.pone.0054381. Epub 2013 Jan 18.

Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes

Charlotte Charpentier  1 , Sidonie Lambert-Niclot, Claudia Alteri, Alexandre Storto, Philippe Flandre, Valentina Svicher, Carlo-Federico Perno, Françoise Brun-Vézinet, Vincent Calvez, Anne-Geneviève Marcelin, Francesca Ceccherini-Silberstein, Diane Descamps
Affiliations

Description of the L76V resistance protease mutation in HIV-1 B and "non-B" subtypes

Charlotte Charpentier et al. PLoS One. 2013.

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Prevalence of the L76V mutation between 1998 and 2010 in a database containing 29,643 sequences issued from clinical samples with any antiretroviral drug resistance.
Figure 2
Figure 2. Proportion of protease inhibitors resistance-associated mutations with the L76V mutation in HIV-1 subtype B samples and in HIV-1 “non-B” samples.
P-values are indicated only if significant.
Figure 3
Figure 3. Dendrograms obtained from average linkage hierarchical agglomerative clustering, showing significant clusters of L76V protease inhibitors resistance mutations among B subtype sequences (A), and among “non-B” subtype sequences (B).
The length of branches reflects distances between mutations in the original distance matrix. Bootstrap values, indicating the significance of clusters, are reported in the boxes.
See this image and copyright information in PMC

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