Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data

Oliver T Stirrup,Anton Pozniak,Caroline A Sabin,Alison Cox,David Asboe,Chloe Orkin,Anna Tostevin,Patricia Cane,David T Dunn,Fabiola Martin

doi:10.1186/s12981-018-0198-7

Abstract

BackgroundThe prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations.MethodsWe considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997–2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case–control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival.ResultsA total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection.ConclusionsThe Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis.

Highlights

The prevalence of human immunodeficiency virus (HIV)-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries
Highly potent and effective antiretroviral therapies (ART) to treat HIV-1 infection are available and drug resistance was a considerable problem in the early years of ART use, its impact has declined in high-income countries
The more recent introduction of widespread ART in low- and middle-income countries (LMICs) has been associated with an increase in transmitted drug resistance [33] and whilst it may be expected that the phase-out of older drug regimens [24] and improved access to viral load (VL) monitoring [11] will lead to an eventual reduction, the overall levels of drug resistance have yet to show such a decline [34]

Summary

Introduction

The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. Potent and effective antiretroviral therapies (ART) to treat HIV-1 infection are available and drug resistance was a considerable problem in the early years of ART use, its impact has declined in high-income countries. Drug resistance remains a considerable problem in the successful treatment of HIV infection in many low- and middle-income countries (LMICs) [5,6,7]. This is in part due to limited drug options, and to a lack of (or limited) routine viral load (VL) monitoring [8] as patients continuing to use ART while failing to suppress viral replication may develop resistance mutations. This has led to calls for improved provision of VL monitoring and resistance testing [9,10,11]

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