Characterization of the patterns of drug-resistance mutations in newly diagnosed HIV-1 infected patients naïve to the antiretroviral drugs

Claudia Alteri,Massimo Ciccozzi,Francesca Ceccherini-Silberstein,Caterina Gori,Massimo Giuliani,Valentina Svicher,Paola Elia,Carlo Federico Perno,Stefano Aviani Bardacci,Roberta Balzano,Roberta D'Arrigo,Nicoletta Orchi,Paola Scognamiglio,Enrico Girardi,Marina Selleri

doi:10.1186/1471-2334-9-111

Abstract

BackgroundThe transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment. To better define this problem, a study in a cohort of newly diagnosed HIV-1 infected individuals has been conducted. This study is aimed to assess the prevalence and the patterns of the mutations recently associated with transmitted drug resistance in the reverse transcriptase (RT) and in protease (PR) of HIV-1.MethodsPrevalence of transmitted drug resistant strains is determined in 255 newly diagnosed HIV-1 infected patients enrolled in different counselling and testing (CT) centres in Central Italy; the Avidity Index (AI) on the first available serum sample is also used to estimate time since infection. Logistic regression models are used to determine factors associated with infection by drug resistant HIV-1 strains.ResultsThe prevalence of HIV-1 strains with at least one major drug resistance mutation is 5.9% (15/255); moreover, 3.9% (10/255) of patients is infected with HIV nucleoside reverse transcriptase inhibitor (NRTI)-resistant viruses, 3.5% (9/255) with HIV non-NRTI-resistant viruses and 0.4% (1/255) with HIV protease inhibitor (PI)-resistant viruses. Most importantly, almost half (60.0%) of patients carries HIV-1 resistant strains with more than one major drug resistance mutation. In addition, patients who had acquired HIV through homosexual intercourses are more likely to harbour a virus with at least one primary resistance mutation (OR 7.7; 95% CI: 1.7–35.0, P = 0.008).ConclusionThe prevalence of drug resistant HIV-1 strains among newly diagnosed individuals in Central Italy is consistent with the data from other European countries. Nevertheless, the presence of drug-resistance HIV-1 mutations in complex patterns highlights an additional potential risk for public health and strongly supports the extension of wide genotyping to newly diagnosed HIV-1 infected patients.

Highlights

The transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment
Our study shows that the prevalence of HIV-1 drug-resistant strains in newly diagnosed patients is 5.9%, in the range described by other European and American reports [11,12,13,14,15,16], and that the majority (60.0%) of these HIV-1 strains carries more than one major drug resistance mutation
By performing a cluster analysis, we observed, in our cohort of newly diagnosed HIV-1 B subtype infected patients, the existence of a complex mutational cluster involving the revertant forms T215D/S and the TAM1 M41L, L210W, the K103N and the polymorphism V60I. This mutation has been shown to rescue the replicative capacity impaired by the major drug resistance mutations in the absence of drug pressure, and to contribute to the persistence over time of major drug resistance mutations in drug naïve patients [30]. Consistent with this finding, patients infected by HIV-1 strain with V60I and TAM1 had an higher viremia than those infected by HIV1 strain with TAM1 only (5.30 versus 3.9 log copies/ml, respectively, P = 0.09); the limited sample size allow us to describe only a trend, that needs to be confirmed in a larger dataset

Summary

Introduction

The transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment. Its frequent detection among HIV-infected treatment failing patients [1,2,3] can in turn increase the risk of new infections driven by drug-resistant viral strains [4]. The presence of drug-resistant HIV-1 strains in drug naïve patients is associated with an increased probability of virological failure to the first-line antiretroviral therapy [6,7,8]. The new guidelines recommend to perform the genotypic resistance testing in all drug naive patients, before beginning a first line antiretroviral regimen [9,10]

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