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

AIDS Research and Therapy

the UK HIV Drug Resistance Database¹  the UK Collaborative HIV Cohort¹  Chloe Orkin²  Oliver T. Stirrup³  Anna Tostevin³  David T. Dunn³  Caroline A. Sabin⁴  Anton Pozniak⁵  David Asboe⁵  Patricia Cane⁶  Fabiola Martin⁷  Alison Cox⁸ 

[1] ;Barts Health NHS Trust;Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, University College London;Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London;Chelsea and Westminster Hospital NHS Foundation Trust;High Containment Microbiology, Public Health England;Hull York Medical School, University of York;Infection and Immunity laboratory, Charing Cross Hospital;

关键词: 151 complex;    69 insertion complex;    HIV;    Multidrug resistance;    Multi-NRTI resistance;    NRTI;   

DOI  :  10.1186/s12981-018-0198-7

来源: DOAJ

【 摘 要 】

Abstract Background 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. 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. Methods We 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. Results A 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. Conclusions The 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.

【 授权许可】

Unknown