The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

Wiesmann, Frank; Vachta, Jan; Ehret, Robert; Walter, Hauke; Kaiser, Rolf; Stürmer, Martin; Tappe, André; Däumer, Martin; Berg, Thomas; Naeth, Gudrun; Braun, Patrick; Knechten, Heribert

doi:10.1186/1742-6405-8-7

Table 1 Active drug score (ADS) for the follow-up therapy

From: The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

	GROUP A										GROUP B
Pat-ID	#1	#2	#4	#12	#14	#17	#18	#21	#22	#46	#3	#5	#8	#9	#10	#11	#16	#19	#24	#25	#26	#27	#31	#33	#37	#39	#40	#41
*Therapy*	ATV SQV RTV FTC	ATV SQV RTV 3TC	ATV SQV RTV	ATV/r SQV 3TC T20	SQV TPV/r 3TC ddI	ddI d4T SQV	ATV SQV 3TC T20	ATV EFV TDF AZT 3TC MVC	ATV/r SQV AZT 3TC TDF	SQV/r TDF FTC	LPV/r SQV 3TC d4T TDF	LPV/r ATV AZT 3TC	LPV/r SQV d4T	LPV/r SQV ENF	LPV ATV FTC TDF	LPV/r ATV EFV	LPV/r SQV	LPV/r SQV	APV SQV TDF	APV SQV ddC d4T	APV/r SQV	LPV/r SQV FTC TDF	LPV/r SQV 3TC ETR	LPV/r SQV AZT 3TC TDF	LPV/r SQV ddI 3TC	LPV/r SQV TDF	LPV/r SQV TDF MVC	LPV/r ATV TDF AZT ABC 3TC
*Rev.-Transcriptase mutations*	41L 44D 67N 98G 103N 118I 210F 215Y 219R	41L 67ss 69S 188L 215Y	41L 118I 184V 215Y	41L 44A 67N 75I 103N 108I 118I 210W 215Y	41L 67N 69D 70R 74V 103N 181C 210W 215F 219Q	67N 70R 103NS 190A 184V 219Q	41L 67N 69E 75I 103N 108I 118I 178M 210W 215Y	41L 67N 74V 101Q 184V 215Y	41L 44D 67N 101E 103N 118I 184V 210W 215Y 219E	n.d.	41L 67ss 69S 101Q 181C 190S 215Y	65R 70R 103N 108I 115F 151M 179E 184V 219E	67N 184V 210W 215Y 219Q	41L 44D 67N 75L 118I 181C 184V 190A 210S 215Y	41L 44D 67N 70R 190A 227L 184V 210W 215F 219R	41L 67N 74V 98G 118I 184V 210W 215Y 227L	41L 44D 103N 118I 184V 210W 215Y	no data	no data	no data	67N 70R 103S 184V 190A 215F 219Q	41L 67N 75I 118I 210W 215F	41L 44A 67N 75M 101Q 118I 184V 210W 215F	41L 74V 101Q 103N 108I 181C 190A 210W 215Y	41L 44D 67G 103N 118I 184V 210W 215F	67N 70R 215I 219Q	67N 70R 215I 219Q	41L 67N 70R 184V
*Protease mutations*	10F 20I 36I 46I 50V 54I/V 76V	10V 46I 47V 71V 76V 77I	10V 20R 36I 46I 76V 90M	10I 33F 46L 76V 82F 90M	10V 20R 33F 36I 54V 73S 76V 90M	10F 20R 46I 54V 63P 76V 82F	10I 33F 36L 46L 76V 82F 84V 90M	10I 53L 54V 71V 76V 77I 82A 84V 90M	10I 33F 46L 54V 71I 76V 77L 82A 90M	10I 33V 60E 76V	10V 46L 54V 63P 71V 82A 93L	10I 20I 36I 46I 54L 76V 84V	20R 32I 46I 76V 82A	10I 24I 33F 46I 54V 63P 71V 76V 82A	10V 20I 36I 46I 47V 53L 76V 84V 90M	10F 33F 46L 54L 71V 76V 77I 84V 90M	10F 46I 54M 71V 76V 82A	10I 20R 24I 36I 46I 54V 76V 82C	10F 33F 54V 71V 76V 77I 82A	10I 20R 35D 46I 54V 76V	10I 20R 36I 46I 54V 71V 76V 82F 90M	10I 46I 47V 71V 76V 90M	10I 13V 32I 33F 36I 46I 76V 84V 90M	10F 46I 47V 76V 84V	10R 32I 33F 46I 47V 76V 84V 88S 90M	10F 20I 36I 46I 76V 84V	10V 13V 24I 33F 46I 54V 76V 82A	20I 36I 54V 76V 82A
Active Drug Scores
HIVdb 4.3.6	[1.5]	(2.25)	0.5	[1.75]	0.75	1,25	[1.5]	[1.75]	0.25	3.0	1,5	[0.5]	[0.75]	1.25	0.25	[0.75]	[0.5]	[0.5]	1.5	n.d.	0.5	[1.25]	[0.25]	[1.5]	0.0	[1.0]	[1.75]	[1.75]
Rega V7.1.1	2.0	(2.75)	1.5	2.0	1.0	1.0	2.0	3.5	0.0	3.0	1.75	[1.0]	[1.5]	1.0	0.0	[0.25]	[0.75]	[0.75]	1.75	n.d.	0.75	[1.0]	[0.5]	2.75	0.5	2.0	2.25	4.25
HIVGrade04/08	2.5	(3.0)	1.5	2.25	1.0	0.5	2.75	2.75	0.0	3.0	(2.0)	[1.0]	[1.0]	(2.0)	0.0	[1.0]	[1.0]	[1.0]	(2.0)	n.d.	1.0	[1.75]	[0.0]	[1.75]	0.0	[0.75]	2.0	2.0
ANRS 10/2007	3.0	(2.0)	0.5	[1.0]	1.0	1.0	2.0	2.5	0.5	3.0	1.5	[0.0]	2.0	1.0	0.5	[1.0]	[1.0]	[0.5]	(2.0)	n.d.	0.5	2.0	[0.5]	2.5	1.5	[1.5]	2.5	3.0
geno2pheno	2.0	(3.0)	1.0	2.5	(2.0)	n.d.	n.d.	2.0	n.d.	3.0	(2.0)	[0.5]	[0.5]	1.5	0.0	[1.0]	n.d.	n.d.	n.d.	n.d.	0.0	2.5	n.d.	2.0	0.0	1.0	2.0	4.0
VircoType	2.25	(2.0)	(2.0)	2.5	1.5	n.d.	n.d.	3.5	n.d.	3.0	2.5	2.0	2.0	1.0	0.5	[0.5]	[1.0]	[1.0]	n.d.	n.d.	0.5	[1.0]	[1.0]	3.0	1.5	2.0	3.0	3.5
*Phenotype*	2.5	n.d.	0.0	n.d.	n.d.	(3.0)	3.0	3.0*	n.d.	n.d.	n.d.	2.5	2.5	(2.0)	n.d.	n.d.	n.d.	[0.5]	n.d.	n.d.	0.0	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.	n.d.
Follow-up
*Baseline VL*	1070	160000	26900	3231	47653	859000	7700	27000	35400	4248	6680	25900	4840	31400	39000	20163	8751	8800	88100	16100	310510	< 50	72100	14900	1300	744	2078	443
*Lowest VL (12-96 weeks)*	< 50	3410	38700	< 50	4943	190	< 50	< 50	1020	< 50	1320	< 50	< 50	116	24000	< 50	< 50	< 50	559	< 50	18270	< 50	< 50	< 50	1300	< 50	< 50	< 50
*VL at week 96*	13589	46570	152000	< 50	20626	LFU	LFU	LFU	16500	LFU	LFU	< 50	< 50	116	LFU	< 50	< 50	LFU	LFU	1777	LFU	391	60	< 50	LFU	< 50	< 50	< 50

Based on five genotypic resistance interpretation tools as well as two phenotypic resistance tests, an active drug score (ADS) for the follow-up therapy was calculated by adding the activity score for every active drug ranging from AS = 1.0 for complete sensitivity, AS = 0.75 for potential low-level resistance, AS = 0.5 for intermediate resistance, AS = 0.25 for possible resistance and AS = 0.0 for complete resistance. Their prediction on follow-up therapy was then compared with the virological response in a time frame of 96 weeks. Sucessfull therapies despite an active drug score prediction of <2 are displayed in bold and square brackets. Unsucessfull therapies despite an active drug score prediction of ≥2 are displayed in round brackets. LFU=loss of follow-up.

Back to article page

ISSN: 1742-6405

Contact us

Submission enquiries: journalsubmissions@springernature.com

AIDS Research and Therapy

Contact us