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

Abstract

ObjectivesTransmission of drug‐resistant HIV‐1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013.MethodsResistance tests conducted in antiretroviral treatment (ART)‐naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society‐USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs.Results TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)‐related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first‐line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART‐naïve.ConclusionsWe observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first‐line ART, including integrase inhibitors, remained reassuringly low.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

“…Unless preexisting kidney or liver damage or high likelihood of transmitted drug resistance exists, the results of these tests should not delay start of ART (evidence rating BIII). 78–81 Testing for CCR5 tropism is recommended each time when considering maraviroc, and HLA-B*5701 testing (only needed once) is recommended before starting abacavir (evidence rating AIa).…”

A cross-sectional study to characterize local HIV-1 dynamics in Washington, DC using next-generation sequencing

“…An overall DRM prevalence of 1.4%, 35.7%, and 15.7% was estimated for PR, RT, and int, respectively. The [40][41][42][43][44][45][46][47][48][49] year-olds in our study had the highest prevalence of DRMs (22.9%), while the [20][21][22][23][24][25][26][27][28][29] year-olds in our study did not show any DRMs. Overall, DRMs caused amino acid changes in only one codon position in PR, while 22 and 9 different codons positions changed in RT and int, respectively, when analyzing the consensus sequences.…”

“…Additionally, this mutation was found to be persistent in the DC HIV-1 viral population since 2005 34 . Previous studies showed that the most important NNRTI mutation currently is 103 N because of its connection to first-line treatment failure [39][40][41] ; a quarter of our DC Cohort participants with one or more DRMs contained this mutation, which was also found to be at a low frequency in the DC HIV-1 viral population since 2005 34 .…”

“…In treatment-naïve participants, both when using consensus sequences and haplotypes, we estimated a low prevalence rate of DRMs (14.3%). Similarly, low prevalence rates have been seen in the past in the US ( 42 ; 15% between 1999 and 2011) and even lower in treatment-naïve individuals in Europe ( 41,(43)(44)(45) ; 10% between 2001 and 2013). Moreover, we also found fewer DRMs in treatment-naïve participants compared to a recent study of PLWH in DC 28 (22.5% between 1994 and 2013).…”

“…The only codon position predicted by FUBAR in the haplotypes was 230 for int, and it is associated with reduced susceptibility to integrase inhibitors (INSTI) 27 . Seven (4,34,41,43,44,45,64) and eight (22,40,84,92,93,95,105,111) codons were inferred to be under positive selection for V1V2 and V3 haplotype sequences, respectively. Interestingly, only a handful of inferred positively selected codons overlapped between the haplotype and consensus sequences, those were at position 35 for RT; positions 201, 265, and 283 for int; 34 for V1V2; and 93 for V3.…”