Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study

被引：41

作者：

Dolling, David ^{[1
]}

Sabin, Caroline ^{[23
]}

Delpech, Valerie ^{[10
]}

Smit, Erasmus ^{[24
]}

Pozniak, Anton ^{[3
]}

Asboe, David ^{[3
]}

Brown, Andrew Leigh

Churchill, Duncan ^{[7
]}

Williams, Ian ^{[28
]}

Geretti, Anna Maria ^{[11
]}

Phillips, Andrew ^{[23
]}

Mackie, Nicola ^{[20
]}

Murphy, Gary

Castro, Hannah

Pillay, Deenan ^{[23
]}

Cane, Patricia ^{[5
]}

Dunn, David

Aitken, Celia ^{[2
]}

Asboe, David ^{[3
]}

Pozniak, Anton ^{[3
]}

Booth, Clare ^{[4
]}

Cane, Patricia ^{[5
]}

Castro, Hannah

Crofts, Jonathan

Dunn, David

Dolling, David ^{[1
]}

Fearnhill, Esther

Porter, Kholoud

Chadwick, David ^{[6
]}

Churchill, Duncan ^{[7
]}

Clark, Duncan ^{[8
]}

Collins, Simon ^{[9
]}

Delpech, Valerie ^{[10
]}

Geretti, Anna Maria ^{[11
]}

Goldberg, David ^{[12
]}

Hale, Antony ^{[13
]}

Hue, Stephane ^{[14
]}

Kaye, Steve ^{[15
]}

Kellam, Paul ^{[16
,17
]}

Lazarus, Linda ^{[18
]}

Leigh-Brown, Andrew ^{[19
]}

Mackie, Nicola ^{[20
]}

Orkin, Chloe ^{[21
]}

Rice, Philip ^{[22
]}

Pillay, Deenan ^{[23
]}

Phillips, Andrew ^{[23
]}

Sabin, Caroline ^{[23
]}

Smit, Erasmus ^{[24
]}

Templeton, Kate ^{[25
]}

Tilston, Peter ^{[26
]}

机构：

[1] UK HIV Drug Resistance Database, MRC Clin Trials Unit, London WC2B 6NH, England

[2] Gartnavel Royal Hosp, Glasgow, Lanark, Scotland

[3] Chelsea & Westminster Hosp, London, England

[4] Royal Free NHS Trust, London, England

[5] Hlth Protect Agcy, Porton Down, England

[6] S Tees Hosp NHS Trust, Middlesbrough, Cleveland, England

[7] Brighton & Sussex Univ Hosp NHS Trust, Brighton, E Sussex, England

[8] St Bartholomews & London NHS Trust, London, England

[9] HIV I Base, London, England

[10] Hlth Protect Agcy, Ctr Infect, London, England

[11] Univ Liverpool, Liverpool, Merseyside, England

[12] Hlth Protect Scotland, Glasgow, Lanark, Scotland

[13] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England

[14] UCL, London WC1E 6BT, England

[15] Imperial Coll London, London, England

[16] Wellcome Trust Sanger Inst, Hinxton, England

[17] UCL Med Sch, London, England

[18] Hlth Protect Agcy, London, England

[19] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland

[20] Imperial NHS Trust, London, England

[21] St Bartholomews Hosp, London, England

[22] St Georges Healthcare Trust, London, England

[23] UCL, Sch Med, London WC1E 6BT, England

[24] Birmingham Heartlands Hosp, Hlth Protect Agcy, Birmingham, W Midlands, England

[25] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland

[26] Manchester Royal Infirm, Manchester, Lancs, England

[27] Guys & St Thomas NHS Fdn Trust, London, England

[28] Mortimer Market Ctr, London, England

[29] Addenbrookes Hosp, Cambridge, England

[30] Kings Coll Hosp London, London, England

来源：

BMJ-BRITISH MEDICAL JOURNAL | 2012年 / 345卷

基金：

英国医学研究理事会;

关键词：

TRANSMISSION; MUTATIONS; REVEALS; ADULTS; VIRUS;

D O I：

10.1136/bmj.e5253

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom. Design Multicentre observational study. Setting All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care. Participants 14 584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009. Main outcome measure Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization. Results 1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t) ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively). Conclusions The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.

引用

页数：7

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