Molecular and epidemiological characterization of HIV-1 infection networks involving transmitted drug resistance mutations in Northern Greece

Skoura, Lemonia; Metallidis, Simeon; Buckton, Andrew J.; Mbisa, Jean L.; Pilalas, Dimitrios; Papadimitriou, Evangelia; Papoutsi, Androniki; Haidich, Anna‐Bettina; Chrysanthidis, Theofilos; Tsachouridou, Οlga; Antoniadou, Zoe; Kollaras, Panagiotis; Nikolaidis, Pavlos; Malisiovas, Nikolaos

doi:10.1093/jac/dkr386

Cited by 18 publications

(23 citation statements)

References 24 publications

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“…In the present study we found a substantial increase in the levels of TDR among newly diagnosed antiretroviral naive HIV‐1‐infected individuals in our region from 2009 to 2011 compared with the period 2000–07 (21.8% vs 12.5%) . This increase was driven by an increase in NNRTI (18.9% vs 5.4%) and NRTI resistance (14.3% vs 7.6%); a reduction was observed in protease inhibitor resistance (1.2% vs 3.3%).…”

Section: Discussionsupporting

confidence: 45%

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011

Skoura

Metallidis

Pilalas

et al. 2013

Clinical Microbiology and Infection

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We conducted a retrospective study on the prevalence and correlates of transmitted drug resistance among newly-diagnosed antiretroviral naive human immunodeficiency virus (HIV) patients in Northern Greece, during the period 2009-11. Transmitted drug resistance was documented in 21.8% of patients enrolled, affecting approximately 40% of subtype A HIV-1-infected individuals. Overcoming challenges due to the ongoing financial crisis, effective preventive measures should be implemented to control further dissemination of resistant HIV strains.

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Section: Discussionsupporting

confidence: 45%

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011

Skoura

Metallidis

Pilalas

et al. 2013

Clinical Microbiology and Infection

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“…Similar results were reported in various countries for different subtypes, with most common transmission of NRTI DRMs [22], [41], [42], [43]. As expected, no integrase inhibitor (InI) transmitted resistance was found, which is consistent to the fact that all infections were acquired before introduction of InI in the clinical practice.…”

Section: Discussionsupporting

confidence: 88%

“…Prevalence of major protease and reverse transcriptase mutations is similar across the variants, however both virologic and immunologic treatment efficacy is similar to the subtype B [19], [20]. In general, frequency of primary drug resistance differs locally in Europe, often being associated with transmission clusters, fluctuates over time and is usually limited to a single class of antiretrovirals [21], [22], [23], [24]. In Poland the prevalence of transmitted drug resistance in the years 2006–2009 ranged from 3.9% to 7.4% [25].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Subtype D Infections among Caucasians from Northwestern Poland—Phylogenetic and Clinical Analysis

et al. 2012

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BackgroundHIV-1 subtype D infections, which are associated with a faster rate of progression and lymphocyte CD4 decline, cognitive deficit and higher mortality, have rarely been found in native Europeans. In Northwestern Poland, however, infections with this subtype had been identified. This study aimed to analyze the sequence and clinical data for patients with subtype D using molecular phylogeography and identify transmission clusters and ancestry, as well as drug resistance, baseline HIV tropism and antiretroviral treatment efficacy.MethodsPhylogenetic analyses of local HIV-1 subtype D sequences were performed, with time to the most recent common ancestor inferred using Bayesian modeling. Sequence and drug resistance data were linked with the clinical and epidemiological information.ResultsSubtype D was found in 24 non-immigrant Caucasian, heterosexually infected patients (75% of females, median age at diagnosis of 49.5 years; IQR: 29–56 years). Partial pol sequences clustered monophyletically with the clades of Ugandan origin and no evidence of transmission from other European countries was found. Time to the most common recent ancestor was 1989.24 (95% HPD: 1968.83–1994.46). Baseline drug resistance to nucleoside reverse transcriptase inhibitors was observed in 54.5% of cases (mutations: M41L, K103N, T215S/D) with evidence of clustering, no baseline integrase or protease resistance and infrequent non-R5 tropism (13.6%). Virologic failure was observed in 60% of cases and was associated with poor adherence (p<0.001) and subsequent development of drug resistance (p = 0.008, OR: 20 (95%CI: 1.7–290).ConclusionsLocal subtype D represented an independently transmitted network with probably single index case, high frequency of primary drug resistance and evidence of transmission clusters.

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“…Because other studies consistently showed regional differences between the drivers of the HIV-1 epidemic [13], [14], this study aimed to characterize the temporal trend in TDR, the factors associated with TDR including TCs and the clinical impact of TDR for a period of 15 years in a regional epidemic, serviced by the Leuven University Hospitals. The data included socio-demographic, clinical and virological variables.…”

Section: Introductionmentioning

confidence: 99%

Trends and Predictors of Transmitted Drug Resistance (TDR) and Clusters with TDR in a Local Belgian HIV-1 Epidemic

et al. 2014

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We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7–11.9), 6.5% (CI: 5.0–8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4–3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4–3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.

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Molecular and epidemiological characterization of HIV-1 infection networks involving transmitted drug resistance mutations in Northern Greece

Abstract: Our findings underline the substantial impact of transmission networks on TDR in our population.

Cited by 18 publications

References 24 publications

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011

HIV-1 Subtype D Infections among Caucasians from Northwestern Poland—Phylogenetic and Clinical Analysis

Trends and Predictors of Transmitted Drug Resistance (TDR) and Clusters with TDR in a Local Belgian HIV-1 Epidemic

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