Abstract

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.

Highlights

  • In recent years, the number of newly diagnosed HIV-1 patients increased in Belgium [1] with a rate of 10.7 per 100,000 population in 2011, one of the highest rates in Europe [2].Studies carried out in Europe and America highlighted the important role of transmission networks in the spread of transmitted drug resistance (TDR) [3,4,5,6,7]

  • HIV-1 patients from Sub-Saharan countries were more likely to be co-infected with hepatitis B than patients from Belgium (60.9% vs. 34.8%; OR: 4.49, 95% Wilson score confidence interval (95% CI) 1.75– 12.15, p,0.001)

  • This result is in line with the 9.5% of the latest national survey that included 285 patients who were newly diagnosed in Belgium between 2003 and 2006 [11]

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Summary

Introduction

The number of newly diagnosed HIV-1 patients increased in Belgium [1] with a rate of 10.7 per 100,000 population in 2011, one of the highest rates in Europe [2].Studies carried out in Europe and America highlighted the important role of transmission networks in the spread of transmitted drug resistance (TDR) [3,4,5,6,7]. The number of newly diagnosed HIV-1 patients increased in Belgium [1] with a rate of 10.7 per 100,000 population in 2011, one of the highest rates in Europe [2]. Three nationwide studies were performed previously in Belgium and reported a TDR prevalence of 29% (67/231; 95% CI: 23.5–35.2) between 1995 and 1998 [9], 7.2% (6/83; 95% CI: 3.4–14.9) in 2000 [10] and 9.5% (27/285, 95% CI: 6.6–13.4) between 2003 and 2006 [11]. Recent reports revealed the rapid onward transmission of an HIV-1 strain with K103N mutation [12] and the involvement of transmission clusters (TCs) in approximately half of patients with TDR [4] in a local HIV epidemic in Belgium

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