Abstract
ObjectiveTo 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.MethodsFrequency 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.ResultsAmong 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).ConclusionsWe 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.
Highlights
The antiretroviral drug class of protease inhibitors (PI) is known to have a high genetic barrier to resistance [1]
When regarding the prevalence of the L76V mutation among the PI-resistant viruses, containing at least one major PI resistance-associated mutations (RAM), it was found at 5.42% (430/7,934)
A similar prevalence of the L76V mutation was observed among B- and ‘‘non-B’’-infected patients until 2008 (Figure 1)
Summary
The antiretroviral drug class of protease inhibitors (PI) is known to have a high genetic barrier to resistance [1]. The recent large clinical trials assessing the efficacy of boosted PI-containing regimen in antiretroviral-naıve patients showed a very low rate of selection of PI resistance-associated mutations (RAM) in case of virological failure [2,3]. Some studies reported a high prevalence of L76V in ‘‘non-B’’ subtypes, in the CRF02_AG recombinant [4,8]. In the MONARK study, assessing lopinavir monotherapy in antiretroviral-naıve patients, the prevalence of the L76V in case of virological failure was 9.4% in this study and all patients displaying L76V-mutated viruses at failure were infected with CRF02_AG recombinant [4]. In a study assessing genotypic resistance profiles in 57 patients living in Cameroon, all infected with HIV-1 ‘‘non-B’’ subtypes, the prevalence of the L76V was 8.8% [8]. Few data are available on the impact of the viral subtype on the selection of the L76V mutation
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