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

Abstract

Background: The 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.

Methods: Prevalence 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.

Results: The 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).

Conclusion: The 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.

Figure 1

Phylogenetic relationships based on pol gene (1302 nt) of the HIV-1 pol gene between the HIV-1 non-B pure subtypes circulating in Italy (shown in bold and underlined) and representative strains of HIV-1 M group (subtypes A, C, D, F1, F2, G, H, J, K) from the Los Alamos HIV Sequence Database. The scale bar indicates 5% nucleotide sequence divergence.* indicates the P value < 0.001 (zero length branch test) and the bootstrap values more than 70%.

Figure 2

Phylogenetic relationships on pol gene (1302 nt) of the HIV-1 pol gene between the HIV-1 putative recombinant forms circulating in Italy (shown in bold and underlined) and the reference sequences of the CRFs of the HIV-1 M group from the Los Alamos HIV Sequence Database. Bootstrap values <90% are not shown. The scale bar indicates 3% nucleotide sequence divergence.* indicates the P value < 0.001 (zero length branch test) and the bootstrap values more than 70%.

Figure 3

Dendrogram obtained from average linkage hierarchical agglomerative clustering, showing significant clusters of RTI resistance mutations. 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.