000 02898cam a2200193 4500
001 NMDX7767
008 120401t2015 xxu||||| |||| 00| 0 eng d
100 _aAinsworth, J.
240 _aHIV Medicine
245 _aDolutegravir in clinical practice: UK experience within the named patient programme
260 _c2015
500 _aNMUH Staff Publications
500 _aEMBASE
500 _a16
520 _a<span style="font-size: 10pt;">Background: Dolutegravir (DTG) is a new integrase inhibitor (INI) with activity against raltegravir resistant virus. In 2011, a named patient programme (NPP) was initiated for patients with INI resistance or where DTG offered potential benefits over existing antiretrovirals. We report the UK experience of the NPP. Methods: Centres accessing DTG for HIV-1 infected patients within the NPP were invited to submit demographic, ART history, resistance, viral load (VL) and CD4 outcomes. Patients were analysed according to known presence (INI-R) or absence (INI-S) of INI mutations. Results: 34 patients were identified from 13 centres, 50% (17) with INI resistance. 5/17 INI-R vs 11/17 INI-S were male, median age was 46 vs 46 years, 8 vs 11 were of white ethnicity and 8 vs 8 were MSM. 3 vs 0 were known to be co-infected with HBV, and 1 vs 1 with HCV. Patients were generally highly ART experienced with significant resistance (see table). 9/17 vs 7/17 had high level resistance (Stanford HIVdb) to darunavir, etravirine or tenofovir. The most common major INI mutations were at positions 155 (n=8), 148 (4), and 140 (3). 5/17 had more than one major INI mutation, 3/5 had Q148 with >=2 secondary mutations from G140A/C/S, E138A/K/T, or L74I. At switch, 14/17 vs 11/17 had a known VL>1000c/ml, with median CD4 93 (range 1-1093) cells/mm</span><sup><span style="font-size: 10pt;">3</span></sup><span style="font-size: 10pt;"> vs 213 (2-490; p=0.90). Median number of additional ARVs in the optimised background regimen was 3 (range 1-6) for INI-R and 2.6 (1-5) for INI-S. For INI-R, VL<50c/ml in 5/9, 7/10 and 5/6 at 12, 24 and 48 weeks respectively, compared to 7/12, 5/7 and 2/3 in those with INI-S virus. In the INI-R group, after a median (range) of 71.1 (2.1-182.9) weeks FU, 10/13 had a final VL<50c/ml, and in the INI-S group, after 13.7 (2.7-62.1) weeks, 8/13 had VL<50c/ml. 4 patients in each group had no prospective FU. 2 stopped DTG after 61 and 166 weeks due to patient choice, and 2 died whilst taking DTG after 17 and 26 weeks. Conclusion: Early experience of DTG on the NNP in this highly treatment experienced group is mixed and likely influenced as much by patient adherence as regimen activity. (Conference abstract)</span>
700 _aWood, C.
700 _aOkoli, C.
856 _uhttp://onlinelibrary.wiley.com/doi/10.1111/hiv.12265/epdf
999 _c76561
_d76561