Epidemiological Surveillance of HIV-1 Transmitted Drug Resistance in Spain in 2004-2012: Relevance of Transmission Clusters in the Propagation of Resistance Mutations

Abstract

Our objectives were to carry out an epidemiological surveillance study on transmitted drug resistance (TDR) among individuals newly diagnosed of HIV-1 infection during a nine year period in Spain and to assess the role of transmission clusters (TC) in the propagation of resistant strains. An overall of 1614 newly diagnosed individuals were included in the study from January 2004 through December 2012. Individuals come from two different Spanish regions: Galicia and the Basque Country. Resistance mutations to reverse transcriptase inhibitors (RTI) and protease inhibitors (PI) were analyzed according to mutations included in the surveillance drug-resistance mutations list updated in 2009. TC were defined as those comprising viruses from five or more individuals whose sequences clustered in maximum likelihood phylogenetic trees with a bootstrap value ≥90%. The overall prevalence of TDR to any drug was 9.9%: 4.9% to nucleoside RTIs (NRTIs), 3.6% to non-nucleoside RTIs (NNRTIs), and 2.7% to PIs. A significant decrease of TDR to NRTIs over time was observed [from 10% in 2004 to 2% in 2012 (p=0.01)]. Sixty eight (42.2%) of 161 sequences with TDR were included in 25 TC composed of 5 or more individuals. Of them, 9 clusters harbored TDR associated with high level resistance to antiretroviral drugs. T215D revertant mutation was transmitted in a large cluster comprising 25 individuals. The impact of epidemiological networks on TDR frequency may explain its persistence in newly diagnosed individuals. The knowledge of the populations involved in TC would facilitate the design of prevention programs and public health interventions.

Recent trends and patterns in HIV‐1 transmitted drug resistance in the United Kingdom

“…In the UK, the prevalence of TDRMs remains higher in MSM than in heterosexuals, consistent with other studies in high‐income countries . This difference has been consistently reported in the UK and can be attributed to historical patterns of HIV acquisition.…”

“…Analysis of TDR in the ART‐naïve UK population has revealed a trend for decreasing prevalence of TDRMs from 2005 to 2013, with 7.5% of individuals tested in recent years (2010–2013) having detectable TDRM. Other European cohort studies have also recently reported temporal trends for decreasing TDR and clinically relevant resistance to first‐line treatments, including Spanish cohorts and the PRIMO cohort in France .…”

Prevalence of Transmitted HIV Drug Resistance Among Recently Infected Persons in San Diego, CA 1996–2013

“…The combined prevalence of TDR to one or more drugs in the first three ART classes was approximately 13.5% over the 18 years of the study. Given the episodic nature of HIV transmission, we expected to observe year-to-year variation in TDR rates, similar to what has been shown in other recent studies [47-49]; however we did observe a significant increase in the overall rate of TDR over time. The TDR rates found from 2005-2013 mirror the most recent CDC study evaluating TDR nationally between 2007 and 2010, which reported a 16.2% rate of TDR among ART-naïve HIV-infected individuals across the United States.…”

Epidemiological trends of HIV‐1 infection in blood donors from Catalonia, Spain (2005‐2014)

“…Finally, we also identified four individuals who were infected with CRF_BG variants, which are even less common in Spain. 31 The prevalence of TDRMs to antiretroviral drugs in Catalonian blood donors was 14%, which was greater than the values recently reported in Barcelona (9%), 12 in the CoRIS population (9.9%), 32 and in Madrid (8.3%). 33 It was also higher than the stable overall TDRM levels of 9.6% in Belgium and 9% in France, where the results were obtained using a study design and time frame similar to the work presented here, 34,35 and higher than the overall trend of 9.4% described in Europe between 2000 and 2013.…”