HIV Drug Resistance Database

version 4.3.2, 2008-01-08

the following PI mutation scores were updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
24I	TPV	2	0
48V/M	ATV	10	25
54L	TPV	5	0
58E	NFV	0	5
58E	TPV	2	5
74P	NFV, TPV	2	10
74S	NFV	0	10
76V	TPV	0	-5
83D	TPV	2	10
84VAC	TPV	25	20

the following NRTI mutation score was updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
115F	TDF	0	10

Relevant reference:

Baxter JD, Schapiro JM, Boucher CA, Kohlbrenner VM, Hall DB, Scherer JR, Mayers DL (2006). Genotypic changes in human immunodeficiency virus type 1 protease associated with reduced susceptibility and virologic response to the protease inhibitor tipranavir. J Virol 80(21):10794-801. Epub 2006 Aug 23.
Deforche K, Silander T, Camacho R, Grossman Z, Soares MA, Van Laethem K, Kantor R, Moreau Y, Vandamme AM; non-B Workgroup (2006).Analysis of HIV-1 pol sequences using Bayesian Networks: implications for drug resistance. Bioinformatics 22(24):2975-9. Epub 2006 Oct 4.
Lanier ER, Givens N, Stone C, Griffin P, Gibb D, Walker S, Tisdale M, Irlbeck D, Underwood M, St Clair M, Ait-Khaled M (2004). Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimens. HIV Med 5(6):394-9.
Margot NA, Miller MD (2005). In vitro combination studies of tenofovir and other nucleoside analogues with ribavirin against HIV-1. Antivir Ther 10(2):343-8.
Rhee SY, Taylor J, Wadhera G, Ben-Hur A, Brutlag DL, Shafer RW (2006). Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proceedings of National Academy of Sciences of the United States of America Oct 25, 2006.
Scherer J, Boucher CA, Baxter JD, Schapiro JM, Kohlbrenner VM, Hall DB (2007). Improving the prediction of virological response to tipranavir: the development of a tipranavir weighted score. [Poster P3.4/07] 11th European AIDS Conference; Madrid, Spain.
Vermeiren H, Van Craenenbroeck E, Alen P, Bacheler L, Picchio G, Lecocq P; Virco Clinical Response Collaborative Team (2007).Prediction of HIV-1 drug susceptibility phenotype from the viral genotype using linear regression modeling. J Virol Methods 145(1):47-55. Epub 2007 Jun 15.
Wirden M, Marcelin AG, Simon A, Kirstetter M, Tubiana R, Valantin MA, Paris L, Bonmarchand M, Conan F, Kalkias L, Katlama C, Calvez V (2005). Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients. J Med Virol 76(3):297-301.

version 4.3.1, 2007-09-25

the following NRTI mutation scores were updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
70G	3TC, FTC	0	10
	ABC	0	20
	DDI	0	25
	TDF	0	15
	D4T	0	0
	AZT	12	0

Relevant reference:

Bradshaw D, Malik S, Booth C, Van Houtte M, Pattery T, Waters A, Ainsworth J, Geretti AM (2007) Characterization of a novel drug-resistance pattern associated with the mutations K70G and M184V in HIV-1 reverse transcriptase. Antimicrob Agents Chemother 2007 Sep 17; [Epub ahead of print].

version 4.3.0.3, 2007-09-22

Almost all comments were updated.

version 4.3.0.2, 2007-08-28

The abbreviation for the NNRTI drug Etravirine was changed from TMC125 to ETV.

version 4.3.0.1, 2007-08-23

the following NNRTI mutation scores were updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
101E	DLV, NVP	20	30
101E	EFV	10	15
138K	DLV, NVP	0	20
138K	EFV	0	10
179F	DLV, NVP	25	30
179F	EFV	10	15
227C	DLV, NVP	0	30
227C	EFV	0	15
318F	DLV	30	50
318F	NVP	12	30

TMC125 was added with the following scores
Mutation	Score
98G	5
98S	0
100I	20
100V	10
101E/P	15
101Q/R	0
101H/N	5
103N/S/T	10
103R/Q/E	5
106A/M	10
106I/L	0
108I	5
138K	20
179D/M	10
179E	10
179I/T/G/A	0
179F	40
181C	30
181I/V	30
181S	10
188C	10
188H	15
188L	20
190A	15
190C/Q/V/T	20
190E/S	30
225H	10
227C	15
227L	10
227Y/S	0
230L	20
234I	0
236L/S	0
238T/N/R	0
318F	0

Relevant references:

Andries K, Azijn H, Thielemans T, Ludovici D, Kukla M, Heeres J, Janssen P, De Corte B, Vingerhoets J, Pauwels R, De Bethune M-P. (2004) TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 48(12):4680-6.
Brillant JE, Klumpp K, Swallow S, Mirzadegan T, Cammack N, Heilek-Snyder G. (2004) In vitro Resistance Development for a second generation NNRTI: TMC125. [Poster 16] XIII International Drug Resistance Workshop; Canary Islands, Spain.
Das K, Clark AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW, Ho CY, Ye H, Lichtenstein MA, Andries K, Pauwels R, De Bethune M-P, Boyer PL, Clark P, Hughes SH, Janssen PA, Arnold E. (2004) Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 47(10):2550-60.
Harrigan PR, Salim M, Stammers DK, Wynhoven B, Brumme ZL, McKenna P, Larder B, Kemp SD. (2002) A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. J Virol 76(13):6836-40.
Katlama C, Campbell T, Clotet B, etal. (2007) DUET-2: 24 week results of a phase III randomised double-blind trial to evaluate the efficacy and safety of TMC125 versus placebo in 591 treatment-experienced HIV-1 infected patients. Abstract (late-breaker) WeSS204:2. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia.
TMC125-C223 Writing Group, Nadler JP, Berger DS, Blick G, Cimoch PJ, Cohen CJ, Greenberg RN, Hicks CB, Hoetelmans RM, Iveson KJ, Jayaweera DS, Mills AM, Peeters MP, Ruane PJ, Shalit P, Schrader SR, Smith SM, Steinhart CR, Thompson M, Vingerhoets JH, Voorspoels E, Ward D, Woodfall B. (2007) Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis. AIDS 21(6):F1-10.
Rhee SY, Taylor J, Wadhera G, Ben-Hur A, Brutlag DL, Shafer RW. (2006) Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proc Natl Acad Sci USA. 103(46):17355-60. Epub 2006 Oct 25.
Sato A, Hammond J, Alexander TN, Graham JP, Binford S, Sugita K, Sugimoto H, Fujiwara T, Patick AK (2006) In vitro selection of mutations in human immunodeficiency virus type 1 reverse transcriptase that confer resistance to capravirine, a novel nonnucleoside reverse transcriptase inhibitor. Antiviral Res 70(2):66-74. Epub 2006 Jan 25.
Su G, Li Y, Paul A, Hang J, Harris S, Hogg H, Dunn J, Yan J, Chow E, Cammack N, Klumpp K, Heilek G. (2007) In vitro Selection and Characterization of Viruses Resistant to R1206, a Novel Nonnucleoside Reverse Transcriptase Inhibitor. XVI International Drug Resistance Workshop; Barbados, Barbados.
Vingerhoets J, Buelens A, Peeters M, Picchio G, Tambuyzer L, Van Marck H, De Smedt G, Woodfall B, De Bethune M-P. (2007) Impact of Baseline NNRTI Mutations on the Virologic Response to TMC 125 in the Phase III Clinical Trials DUET-1 and DUET-2. [Oral Presentation] [Poster 32] XVI International Drug Resistance Workshop; Barbados, Barbados.
Vingerhoets J, Janssen P, Welkenhuysen-Gybels J, Peeters M, Cao-Van K, Tambuyzer L, Woodfall B, De Bethune M-P. (2006) Impact of baseline K103N or Y181C on the virological response to the NNRTI TMC125: analysis of study TMC125-C223. [Poster 17] XV International Drug Resistance Workshop; Sitges, Spain.
Vingerhoets J, Azijn H, Fransen E, De Baere I, Smeulders L, Jochmans D, Andries K, Pauwels R, De Bethune M-P. (2005) TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J Virol 79(20):12773-82.
Vingerhoets J, De Baere I, Azijn H, Van den Bulcke T, McKenna P, Pattery T, Pauwels R, De Bethune M-P. (2004) Antiviral Activity of TMC125 against a Panel of Site-directed Mutants Encompassing Mutations Observed in vitro and in vivo. [Poster 621] 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA.
Vingerhoets J, Van Marck H, Velderman J, Peeters M, McKenna P, Pauwels R, De Bethune M-P. (2003) Antiviral Activity of TMC125, a Potent Next-Generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), against >5000 Recombinant Clinical Isolates exhibiting a wide range of NNRTI Resistance. [abstract 8] 12th International HIV Drug Resistance Workshop; Los Cabos, Mexico.

version 4.2.9, 2007-05-30

Updated PR and RT comments.

version 4.2.8, 2007-05-10

the following NRTI mutation scores were updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
70E	3TC, FTC	0	15
70E	ABC, DDI	0	25
70E	TDF	8	25
70E	AZT	12	0

Relevant references:

Delaunay C, Brun-Vezinet F, Landman R, Collin G, Peytavin G et al. (2005) Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021). J Virol 79(15): 9572-9578
Gallant JE, Rodriguez AE, Weinberg WG, Young B, Berger DS et al. (2005) Early Virologic Nonresponse to Tenofovir, Abacavir, and Lamivudine in HIV-Infected Antiretroviral-Naive Subjects. J Infect Dis 192(11): 1921-1930.
Ross L, Gerondelis P, Liao Q, Wine B, Lim ML et al. (2005) Selection of the HIV-1 reverse transcriptase mutation K70E in antiretroviral-naive subjects treated with tenofovir/abacavir/lamivudine therapy [abstract 92]. Antiviral Therapy 10 (Supplement 1): S102.
Sluis-Cremer N, Sheen CW, Zelina S, Argoti Torres PS, Parikh UM et al. (2006) Molecular Mechanism by which K70E in HIV-1 Reverse Transcriptase Confers Resistance to Nucleoside Reverse Transcriptase Inhibitors. Antimicrob Agents Chemother.
Van Houtte M, Staes M, Geretti A, Pattery T, Bacheler L (2006) NRTI resistance associated with the RT mutation K70E in HIV-1. Antivir Ther 11: S160.

version 4.2.6, 2006-12-12

the following PI mutation score was updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
82L	TPV	30	40

Relevant references:

Baxter JD, Schapiro JM, Boucher CA, Kohlbrenner VM, Hall DB, Scherer JR, Mayers DL. (2006) Genotypic changes in human immunodeficiency virus type 1 protease associated with reduced susceptibility and virologic response to the protease inhibitor tipranavir. J Virol. 80(21):10794-801.
Doyon L, Tremblay S, Bourgon L, Wardrop E, Cordingley MG. (2005). Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res. 68(1):27-35.

version 4.2.5, 2006-12-04

the following PI mutations scores were updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
20ILMRTV	All PIs	1	0
63P	All PIs	1	0
16E	ATV	2	0
77I	NFV	2	0

Other changes included:

The list of major and minor protease inhibitor resistance mutations has been updated:
- L76V has been added to the list of major mutations.
- L23I, L24IF, L33FI, F53LY, G73ACST have been moved from the major mutation category to the minor mutation category.
- Mutations at positions 20, 36, 63, and 77 have been moved from the minor mutation category to the other mutation category because they are highly polymorphic (meaning they occur commonly in the absence of therapy) and because in many cases substitutions at these positions represent the consensus amino acid in one or more non-B subtypes (Rhee AIDS 2006). Moreover, their contribution to decrease susceptibility is minimal and depends entirely on the presence of other mutations.
  In contrast, mutations at positions 10 and 71 occur in about 10% and 5% of PI-naive sequences from all subtypes and steadily increase in frequency with increasing therapy. Two mutations at position 10 (L10F/R) and one at position 71 (A71I) are also nonpolymorphic and remain as minor mutations.
- V11I, E35G, K43T, Q58E, T74P, N83D, and L89V have been added to the minor mutation list.
The list of atypical mutations was updated.
In the "Mutation Scoring" tables, all mutations with scores are shown.
Atypical mutations are shown first.

All mutations at one of the major positions will appear in the "PI Major Resistance Mutations" list except for V82I which will appear in the "PR Other Mutations" list because it is polymorphic for most subtypes and is the consensus for subtype G.
Mutations at a minor position that are not on the minor mutation list will appear in "PR Other Mutations".

Class	resistance positions with their most common / well-recognized mutations
PI Major	D30N, V32I, M46ILV, I47VA, G48VM, I50VL, I54VMLTAS, L76V, V82ATFTLSMC, I84VAC, N88DSTG, L90M
PI Minor	L10IVFRY, V11I, L23I, L24IF, L33FI, E35G, K43T, F53LY, Q58E, A71VTI, G73CATS, T74P, N83D, L89V

Short summary descriptions of each of these mutations (as well as several others that are less clinically relevant) can be found at http://hivdb.stanford.edu/cgi-bin/PIResiNote.cgi and using the mouse-over feature on the mutations listed on the left side of the page.

Relevant references:

Pellegrin I, Breilh D, Ragnaud JM, Boucher S, Neau D, Fleury H, Schrive MH, Saux MC, Pellegrin JL, Lazaro E, Vray M. (2006). Virological responses to atazanavir-ritonavir-based regimens: resistance-substitutions score and pharmacokinetic parameters (Reyaphar study). Antivir Ther. 11(4):421-9.
Rhee SY, Kantor R, Katzenstein DA, Camacho R, Morris L, Sirivichayakul S, Jorgensen L, Brigido LF, Schapiro JM, and Shafer RW for the international Non Subtype B HIV-1 Working Group (2006). HIV-1 pol mutation frequency by subtype and treatment experience: extension of the HIVseq program to seven non-B subtypes. AIDS 20(5):643-651.

version 4.2.4, 2006-11-21

the following PI mutations scores were updated
Mutation	Drugs	Score
Mutation	Drugs	Old	New
20ILMRTV	All PIs	2	1
71T	All PIs	2	1
74P	NFV, SQV, TPV	0	2
33F	TPV	20	8
35G		0	2
43T		0	2
50V		0	-5
58E		0	2
82S		20	15
83D		0	2
90M		5	6
16E	ATV	5	2

Other changes included:

drug name abbreviation for Prezista (darunavir) was changed from TMC114 to DRV
drug name abbreviation for Lexiva (fosamprenavir) was changed from fAPV to FPV
PI, NRTI, and NNRTI Comments were updated.

Relevant references:

Baxter JD, Schapiro JM, Boucher CA, Kohlbrenner VM, Hall DB,Scherer JR, Mayers DL. (2006). Genotypic changes in human immunodeficiency virus type 1 protease associated with reduced susceptibility and virologic response to the protease inhibitor tipranavir. J Virol. 80(21):10794-801.
Elston R, Scherer J, Hall D, Schapiro J, Bethell R, Kohlbrenner V and Mayers D. (2006). De-selection of the I50V mutation occurs in clinical isolates during aptivus/r (tipranavir/ritonavir)-based therapy. Antivir Ther. 11:s102.
Pellegrin I, Breilh D, Ragnaud JM, Boucher S, Neau D, Fleury H, Schrive MH, Saux MC, Pellegrin JL, Lazaro E, Vray M. (2006). Virological responses to atazanavir-ritonavir-based regimens: resistance-substitutions score and pharmacokinetic parameters (Reyaphar study). Antivir Ther. 11(4):421-9.
Piliero PJ, Parkin N, Mayers D. (2006). Impact of protease mutations L33F, V82A, I84V, and L90M on ritonavir (RTV)-boosted protease inhibitor susceptibility. 46th ICAAC. September 27-30, 2006. San Francisco. Abstract H-998.

version 4.2.3, 2006-10-11

PI
the following mutations were updated:
Mutation	Drugs	Score
Mutation	Drugs	Old	New
10F	TMC114	4	2
32I		12	10
54L		12	10
46V		8	6
76V		8	12
36I/L/V/T/A	All PIs	1	0
63P	All PIs	2	1

version 4.2.2, 2006-09-18

PI
the following mutations were updated:
Mutation	Drugs	Score
Mutation	Drugs	Old	New
46I/L	TMC114	8	6
54S/T/V/A
82F/A/S/T/M/L/C
90M
53L	All PIs	5	3

PI Comments were updated.

version 4.2.1, 2006-07-31

TMC114 was added with the following scores:

Mutation	Score
10F	4
10I/R/V/Y	2
11I	4
11F/T/C	0
16A/E	0
20I/M/R/T/V/L	2
23I	0
24I	2
24F	1
30N	0
32I	12
32A	5
33F	5
33V/I	0
36I/L/V/T/A	1
46I/L/V	8
47V	12
47A	10
48V/M/A/S/T	0
50V	20
50L	0
53L/Y	5
54L/M	12
54S/T/V/A	8
63P	2
71T/V/I	2
73C	2
73S/T	5
73A	2
76V	8
77I	0
82A/F	8
82I	0
82S/T/M/L/C	8
84A/V/C	12
88D/S/T/G	0
89V	4
89I/T	2
89M	0
90M	8
93L/M	0

A number of new mutations were added to PIs with the following scores:

Mutation	Drugs	Score
11I	fAPV	4
11I	ATV, IDV, LPV, NFV, SQV, TPV	2
11F/T/C	All PIs	0
76V	fAPV, IDV	12
	NFV	5
	SQV, ATV	-5
	LPV	8
	TPV	0
89V	fAPV, NFV	4
	IDV	2
	SQV, LPV, ATV, TPV	1
89I/T	fAPV, NFV	2
89I/T	IDV, SQV, LPV, ATV, TPV	1
89M	All PIs	0

Ritonavir has been removed from the report because it is rarely, if ever, used except at low doses as a pharmacologic booster thus making it increasingly difficult to develop meaningful interpretations for this drug as the sole PI.

Comments were updated to reflect new PI drug TMC114.

Relevant references:

De Meyer S, Hill A, De Bacre I, Rimsky L, et al (2006). Effect of baseline susceptibility and on-treatment mutations on TMC114 and control PI efficacy: preliminary analysis of data from PI-experienced patients from POWER 1 and POWER 2. [Abstract 157] 13th Conference on Retroviruses and Opportunistic Infection; Denver, Colorado.
De Meyer S, Vangeneugden T, Lefebvre E, et al (2006). Phenotypic and genotypic determinants of resistance to TMC114: pooled analysis of POWER 1, 2 and 3. [Abstract 73] XV International Drug Resistance Workshop; Sitges, Spain.
Tibotec, Inc. (2006). Prezista (darunavir, TMC114) prescribing information. PDF version

version 4.2.0, 2006-05-24

NRTI
The following mutation was added
Mutations	Drugs	Score
65N	3TC, FTC, TDF, DDI	15
	ABC	10
	AZT, D4T	0

Relevant references:

Ross LL, Dretler R, Gerondelis P, Rouse EG, Lim ML, Lanier ER (2006). A rare HIV reverse transcriptase mutation, K65N, confers reduced susceptibility to tenofovir, lamivudine and didanosine. AIDS20(5):787-9.

version 4.1.9, 2006-02-24

PI
Mutation	Drugs	Old Score	New Score
47V	TPV	8	10
54L/M/S/T		10	5
54A		10	15
82T		20	25

Relevant references:

Parkin N and Chappey C. (2005). Protease mutations associated with higher or lower than expected Tipranavir (TPV) susceptibility basd on the TPV mutation score [poster 637]. 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO.

PI
The following mutations were added
Mutations	Drugs	Score
20V/L	All PIs	2
32A	All PIs	5
36T/A	All PIs	1
48A/S/T	SQV	30
	NFV	15
	IDV, RTV, LPV, ATV	5
	fAPV, TPV	0
82C	IDV, NFV, RTV, LPV, TPV	10
82C	fAPV, SQV, ATV	5
All Z scores were removed

NNRTI
The following mutations were added
Mutations	Drugs	Score
100V	All NNRTIs	10
101H/N	DLV, NVP	15
101H/N	EFV	10
103E	DLV, NVP	15
103E	EFV	10
106L	DLV, NVP	10
106L	EFV	5
179M	All NNRTIs	10
179T/G/A	All NNRTIs	0
179F	DLV, NVP	25
179F	EFV	10
181S	DLV, NVP	30
181S	EFV	10
190T	EFV, NVP	60
190T	DLV	0
227S	All NNRTIs	0
227Y	DLV, EFV	0
227Y	NVP	10
236S	DLV	25
236S	EFV, NVP	0
All Z scores were removed

NRTI
The following mutations were added
Mutations	Drugs	Score
67E	3TC, FTC, TDF	0
	ABC, DDI	5
	AZT, D4T	10
67S/T/H	3TC, FTC	0
67S/T/H	ABC, AZT, D4T, DDI, TDF	5
69E	All NRTIs	2
70T/S/N	3TC, FTC, ABC, DDI, TDF	0
70T/S/N	AZT, D4T	5
75L	3TC, FTC	0
75L	ABC, AZT, D4T, DDI, TDF	2
151L	3TC, FTC, TDF	10
151L	ABC, AZT, D4T, DDI	20
210S/M	All NRTIs	0
219W	3TC, FTC	0
	ABC, DDI, TDF	5
	AZT, D4T	10
219T	3TC, FTC, ABC, DDI, TDF	0
	D4T	5
	AZT	10
All Z scores were removed

version 4.1.8, 2006-01-31

PI
Mutation	Drugs	Old Score	New Score
10F	fAPV, ATV, IDV, LPV, NFV, RTV, SQV	3	4
54A	fAPV, ATV, IDV, LPV, NFV, RTV, SQV	5	10
82L	fAPV, ATV, IDV, LPV, NFV, RTV, SQV	NA	10
FPV was renamed fAPV

TPV was added with the following scores:

Mutation	Score
10F/I/R/Y	2
10V	3
10 (Not F/I/R/V/Y)	0
16A/E	0
16 (Not A/E)	0
20I/M/R/T	2
20 (Not I/M/R/T)	2
23I	0
24I	2
24F	1
24 (Not I/F)	1
30N	0
30 (Not N)	0
32I	8
32 (Not I)	5
33F	20
33V/I	0
33 (Not F/V/I)	0
36I/L/V	1
36 (Not I/L/V)	0
46I/L/V	8
46 (Not I/L/V)	5
47V	8
47A	5
47 (Not V/A)	0
48V/M	10
48 (Not V/M)	5
50V/L	0
50 (Not V/L)	0
53L	5
53Y	2
53 (Not L/Y)	0
54L/M/T/S/V/A	10
54 (Not L/M/T/S/V/A)	5
63P	2
63 (Not P)	0
71T/I	2
71V	3
71 (Not T/V/I)	2
73C/S/T/A	2
73 (Not C/S/T/A)	2
77I	0
77 (Not I)	0
82A/M	10
82F	15
82S/T	20
82I	0
82L	30
82 (Not A/F/I/S/T/M/L)	15
84A/V/C	25
84 (Not A/V/C)	20
88D/S/T/G	0
88 (Not D/S/T/G)	0
90M	5
90 (Not M)	10
93L/M	0
93 (Not L/M)	0

Relevant references:

Doyon L, Tremblay S, Bourgon L, Wardrop E, Cordingley MG. (2005). Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res. 68(1):27-35.
Larder BA, Hertogs K, Bloor S, van den Eynde CH, DeCian W, Wang Y, Freimuth WW, Tarpley G. (2000). Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS. 14(13):1943-8.
Boehringer Ingelheim Pharmaceuticals, Inc. (2006). Aptivus (Tipranavir) prescribing information. PDF version

version 4.1.7, 2006-01-20

PI
Mutation	Drugs	Old Score	New Score
G16E	ATV	NA	5
G16E	APV, IDV, LPV, NFV, RTV, SQV	NA	0
G16A	APV, ATV, IDV, LPV, NFV, RTV, SQV	NA	0
G16 (Not A/E)	APV, ATV, IDV, LPV, NFV, RTV, SQV	NA	0
L33F	ATV	3	5
V82A	ATV	20	15
APV was renamed FPV

NRTI
Mutation	Drugs	Old Score	New Score
T69deletion	ABC, ddI	15	25
	AZT, D4T	15	30
	TDF	10	15
K70R	D4T	5	10
L74V	ddI	50	55
L74V	ABC	25	30
L74I	ddI	25	30
M184V/I	ddI	10	5
M184V/I	TDF	-5	-8
M184 (Not V/I)	ddI	10	0
T215C/D/E/I/S/V	D4T	15	20
T215F	ddI	15	20
T215F/Y	D4T	25	30
T215 (Not C/D/E/F/I/S/V/Y)	ABC, ddI, TDF	5	0
T215 (Not C/D/E/F/I/S/V/Y)	D4T	5	10
T219E/N/Q	ABC, ddI, TDF	5	0

NNRTI
Mutation	Drugs	Old Score	New Score
K101E	DLV, NVP	10	20
K101P	DLV, EFV, NVP	20	30
K103N	DLV	70	60
Y188L	DLV	25	30
G190E/Q	DLV	12	15
G190C	DLV	12	0
G190V	NVP, EFV	NA	60
G190V	DLV	NA	0
P225H	DLV	-10	0
M230L	DLV	70	60
P236L	DLV	50	60
P236L	NVP, EFV	-10	0
K238T	EFV	12	15

Comments were updated accordingly.

Relevant references:

Huang, W., A. Gamarnik, K. Limoli, C. J. Petropoulos, and J. M. Whitcomb. (2003). Amino acid substitutions at position 190 of human immunodeficiency virus type 1 reverse transcriptase increase susceptibility to delavirdine and impair virus replication. J. Virol. 77:1512-23.
Marcelin, A. G., P. Flandre, J. Pavie, N. Schmidely, M. Wirden, O. Lada, D. Chiche, J. M. Molina, and V. Calvez. (2005). Clinically relevant genotype interpretation of resistance to Didanosine. Antimicrob. Agents Chemother. 49:1739-44.
Parkin, N. T., S. Gupta, C. Chappey, and C. J. Petropoulos. (2006). The K101P and K103R/V179D Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Resistance to Nonnucleoside Reverse Transcriptase Inhibitors. Antimicrob. Agents Chemother. 50:351-4.
Vora, S., A. G. Marcelin, H. F. Gunthard, P. Flandre, H. H. Hirsch, B. Masquelier, A. Zinkernagel, G. Peytavin, V. Calvez, L. Perrin, and S. Yerly. (2006). Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitor-experienced patients. Aids 20:35-40.

version 4.1.4, 2005-06-20

PI
Mutation	Drugs	Old Score	New Score
V82M	APV,ATV,LPV,NFV,RTV,SQV	NA	10
V82M	IDV	NA	15

NRTI
Mutation	Drugs	Old Score	New Score
K70R/E	TDF	0	8

Comments were updated accordingly.

Relevant references:

Delaugerre C, Roudiere L, Peytavin G, Rouzioux C, Viard JP, Chaix ML (2005). Selection of a rare resistance profile in an HIV-1-infected patient exhibiting a failure to an antiretroviral regimen including tenofovir DF. J Clin Virol. 2005 Mar; 32(3): 241-4.
L Ross, P Gerondelis, Q Liao, B Wine, M Lim, M Shaefer, A Rodriguez, K Limoli, W Huang, NT Parkin, J Gallant, R Lanier (2005). Selection of the HIV-1 Reverse Transcriptase Mutation K70E in Antiretroviral-Naive Subjects Treated with Tenofovir/Abacavir/Lamivudine Therapy. [abstract 92] Antivir. Ther. Volume 10:S102
R Camacho, AR Godinho, P Gomes, A Abecasis, A-M Vandamme, C Palma, AP Carvalho, J Cabanas, K Goncalves (2005). Different substitutions under drug pressure at protease codon 82 in HIV-1 subtype G compared to subtype B infected individuals including a novel I82M resistance mutation. [abstract 138] Antivir. Ther. Volume 10:S151

version 4.1.3, 2005-05-26

Updated the <ALG_VERSION> tag in the xml to reflect the version number instead of the month.

version 4.1.2, 2005-04-11

PI
Mutation	Drugs	Old Score	New Score
N88S	NFV	25	40
N88D	SQV	5	10
V82I	APV,NFV	5	0

NNRTI
Mutation	Drugs	Old Score	New Score
K101Q	DLV,EFV,NVP	5	0

Relevant references:

Eoin Coakley, M Mass, and N Parkin (2005). Atazanavir Resistance in a Protease Inhibitor-nave Patient Treated with Atazanavir/Ritonavir Associated with Development of High-level Atazanavir Resistance and the N88S Mutation in Protease. [abstract 716] Conference on Retroviruses and Opportunistic Infections, Boston, MA.

version 4.1.1, 2005-04-05

NNRTI
Mutation	Drugs	Old Score	New Score
V106M	DLV,EFV,NVP	50	60

version 4.1, 2005-03-17

Protease
Mutation	Drugs	Old Score	New Score
N88S	IDV	5	10
N88S	ATV	15	30
N88T	RTV	5	0
N88G	APV, RTV, LPV	NA	0
	IDV, SQV	NA	5
	ATV	NA	15
	NFV	NA	25

NRTI
Mutation	Drugs	Old Score	New Score
M41L	3TC, FTC	0	4
L210W		0	4
T215F/Y		0	4
T69insert		20	25
L74I	ABC	12	20
L74V		20	25
Y115F		20	25

Relevant references:

Soo-Yon Rhee, Tommy Liu, Jaideep Ravela, Matthew J. Gonzales and Robert W. Shafer (2004). Distribution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Mutation Patterns in 4,183 Persons Undergoing Genotypic Resistance Testing. Antimicrobial Agents and Chemotherapy 48(8):3122-3126
Eoin Coakley, M Mass, and N Parkin (2005). Atazanavir Resistance in a Protease Inhibitor-nave Patient Treated with Atazanavir/Ritonavir Associated with Development of High-level Atazanavir Resistance and the N88S Mutation in Protease. [abstract 716] Conference on Retroviruses and Opportunistic Infections, Boston, MA.

version 4.0, 2004-10-27

Protease
Mutation	Drugs	Old Score	New Score
L10F	All	2	3
L23I	NFV	0	15
L24F	All	2	1
L33F	APV,RTV,LPV	3	5
M36I/V/L	All	2	1
M46I	APV	20	12
M46L	APV	15	12
M46V	APV	15	10
M46I/L	IDV,RTV, LPV	10	12
M46V	LPV	5	10
M46I/L	ATV	10	15
M46L	NFV	20	25
I47V	IDV	10	5
I47A	LPV	20	40
G48V/M	APV	10	5
G48V/M	LPV	5	10
G48M	SQV	40	50
I50V	APV	40	50
I50L	ATV	40	50
F53L	SQV	10	5
F53Y	SQV	5	2
I54V	SQV	10	15
I54A	ATV	10	5
A71V	All	4	3
G73C/S/T	SQV	5	10
G73S/C/T/A	APV,LPV	5	2
V77I	NFV	1	2
V82A/F/S/T	LPV	18	20
V82I	NFV	10	5
I84V	APV,NFV,SQV	40	35
I84A	APV	40	35
	RTV	25	35
	ATV	20	25
I84C	RTV	15	20
N88D/S	RTV	5	0
	SQV	2	5
	LPV	3	0
N88S/T	ATV	10	15
N88T	SQV	2	5
I93L	All	1	0

Relevant references:

Clevenbergh, P., R. Boulme, M. Kirstetter, and P. Dellamonica. 2004. Efficacy, safety and predictive factors of virological success of a boosted amprenavir-based salvage regimen in heavily antiretroviral-experienced HIV-1-infected patients. HIV Med 5:284-8.
Colonno, R., R. Rose, C. McLaren, A. Thiry, N. Parkin, and J. Friborg. 2004. Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens. J. Infect. Dis. 189:1802-10.
Colonno, R. J., A. Thiry, K. Limoli, and N. Parkin. 2003. Activities of Atazanavir (BMS-232632) against a Large Panel of Human Immunodeficiency Virus Type 1 Clinical Isolates Resistant to One or More Approved Protease Inhibitors. Antimicrob. Agents. Chemother. 47:1324-33.
Johnston, E., M. A. Winters, S. Y. Rhee, T. Merigan, C. A. Schiffer, and R. W. Shafer. 2004. A novel HIV-1 protease substrate-cleft mutation, L23I: Association with protease inhibitor therapy and in vitro resistance. Antimicrob Agents Chemother (In press).
Marcelin, A. G., C. Lamotte, C. Delaugerre, N. Ktorza, H. Ait Mohand, R. Cacace, M. Bonmarchand, M. Wirden, A. Simon, P. Bossi, F. Bricaire, D. Costagliola, C. Katlama, G. Peytavin, and V. Calvez. 2003. Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Antimicrob. Agents. Chemother. 47:594-600.
Mo, H., N. Parkin, K. Stewart, L. Lu, T. Dekhtyar, D. Kempf, and A. Molla. 2003. I84A and I84C mutations in protease confer high-level resistance to protease inhibitors and impair replication capacity Antivir. Ther. Volume 8:S56.
Parkin, N., C. Petropoulos, C. Chappey, J. Friend, T. Liegler, J. Martin, and S. Deeks. 2004. Isolated lopinavir resistance after virological rebound of a lopinavir/ritonavir-based regimen Antivir. Ther. Volume 9:S79.
Parkin, N. T., C. Chappey, and C. J. Petropoulos. 2003. Improving lopinavir genotype algorithm through phenotype correlations: novel mutation patterns and amprenavir cross-resistance. AIDS 17:955-61.
Rhee SY, Liu T, Ravela J, Gonzales MJ and Shafer RW. 2004. Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother 48:3122-6
Yerly, S., S. Vora, H. Günthard, P. Vernazza, H. Furrer, A. Zinkernagel, B. Hirschel, L. Perrin, and t. S. H. C. S. (SHCS). 2004. Virological response following switch to atazanavir/ritonavir in relation to baseline genotypic resistance pattern Antivir. Ther. Volume 9:S165
Genotype-phenotype correlations in Stanford HIVRT&PrDB

NRTI
Mutation	Drugs	Old Score	New Score
E44D/A	3TC,FTC	8	5
T69A/I/S	3TC,FTC	5	2
T69insertion	3TC,FTC	30	20
V75I, F77L, F116Y	3TC,FTC	4	5
V118I	3TC,FTC	8	5
M41L	D4T	12	15
A62V	AZT,D4T	5	2
K65R	AZT	0	-5
67deletion	AZT	18	30
67deletion	D4T	12	30
D67N/G/E	AZT	18	15
T69A/I/S	AZT,D4T	5	2
T69insertion	AZT,D4T	25	30
T69D/N	D4T	12	10
T69G	D4T	5	10
L74V	AZT	-8	-5
L74I	AZT	-8	0
V75A/I	D4T	20	10
V75T	D4T	50	30
L210W	AZT,D4T	12	15
T215C/D/E	D4T	5	15
T215S	D4T	10	15
K219Q/E/N	AZT	18	15
K219Q/E/N	D4T	12	10
M41L	DDI,TDF	10	12
A62V	ABC,DDI	5	2
K65R	ABC	20	25
67deletion	ABC	10	25
	DDI	5	25
	TDF	5	15
D67N/G/E	ABC	10	8
D67N/G/E	DDI	5	8
T69insertion	ABC	25	30
T69N	DDI	20	10
T69S/A/I	ABC,TDF	5	2
T69A/I	DDI	10	5
T69G	DDI	5	20
K70R	ABC,DDI,TDF	5	0
L74V	ABC	25	20
L74I	ABC	25	12
L74I	DDI	50	25
V75A/I/M/T	TDF	3	5
F77L	TDF	2	5
Y115F	ABC	15	20
F116Y	TDF	3	5
M184V/I	ABC	16	12
	DDI	12	10
	TDF	-8	-5
L210W	DDI	10	12
T215Y	DDI	12	20
T215F	DDI	12	15
T215C/D/E/I/V/S	ABC,TDF	5	10
T215C/D/E/S	DDI	0	10
T215I/V	DDI	5	10
K219Q/E/N	ABC	10	5
K219R	ABC	10	0
K219R	TDF	5	0

Relevant references:

Brun-Vezinet, F., D. Descamps, A. Ruffault, B. Masquelier, V. Calvez, G. Peytavin, F. Telles, L. Morand-Joubert, J. L. Meynard, M. Vray, and D. Costagliola. 2003. Clinically relevant interpretation of genotype for resistance to abacavir. AIDS 17:1795-1802.
De Luca, A., M. Vendittelli, F. Baldini, S. Di Giambenedetto, M. P. Trotta, A. Cingolani, A. Bacarelli, C. Gori, C. F. Perno, A. Antinori, and G. Ulivi. 2004. Construction, training and clinical validation of an interpretation system for genotypic HIV-1 drug resistance based on fuzzy rules revised by virological outcomes. Antivir. Ther. 9:583-93.
Elion, R., C. Cohen, E. DeJesus, R. Redfield, J. Gathe, R. Hsu, L. Yau, L. Ross, B. Ha, E. Lanier, and T. Scott. 2004. COL40263: Resistance and efficiacy of once-daily trizivir and tenofovir DF in antiretroviral naive subjects [abstract 53]. 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA.
Lanier, E., M. Ait-Khaled, J. Scott, C. Stone, T. Melby, G. Sturge, M. St Clair, H. Steel, S. Hetherington, G. Pearce, B. Spreen, and S. Lafon. 2004. Antiviral efficacy of abacavir in antiretroviral-therapy experienced adults harbouring HIV-1 with specific patterns of resistance to nucleoside reverse transcriptase inhibitors. Antivir. Ther. 9:37-45.
Lanier, E., D. Irlbeck, L. Ross, P. Gerondelis, M. R. Underwood, N. Parkin, C. Chappey, and M. St Clair. 2003. Prediction of NRTI options by linking RT genotype and phenotype breakpoings [abstract 586]. 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA.
Marcelin, A., P. Flandre, J. Pavie, N. Schmidely, M. Wirden, O. Lada, D. Chiche, M. Bernard, J. Molina, and V. Calvez. 2004. New genotypic score comprising mutations impacting negatively and positively the virological response to didanosine in treatment-experienced patients from the randomized didanosine add on Jaguar study Antivir. Ther. Volume 9:S146.
Masquelier, B., E. Race, C. Tamalet, D. Descamps, J. Izopet, C. Buffet-Janvresse, A. Ruffault, A. S. Mohammed, J. Cottalorda, A. Schmuck, V. Calvez, E. Dam, H. Fleury, and F. Brun-Vezinet. 2001. Genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 variants with insertions or deletions in the reverse transcriptase (RT): multicenter study of patients treated with RT inhibitors. Antimicrob. Agents. Chemother. 45:1836-42.
Masquelier, B., C. Tamalet, B. Montes, D. Descamps, G. Peytavin, L. Bocket, M. Wirden, J. Izopet, V. Schneider, V. Ferre, A. Ruffault, P. Palmer, A. Trylesinski, M. Miller, F. Brun-Vezinet, and D. Costagliola. 2004. Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients. Antivir. Ther. 9:315-23.
Miller, M. D., N. Margot, B. Lu, L. Zhong, S. S. Chen, A. Cheng, and M. Wulfsohn. 2004. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. J. Infect. Dis. 189:837-46.
Rhee SY, Liu T, Ravela J, Gonzales MJ and Shafer RW. 2004. Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother 48:3122-6
Violin, M., A. Cozzi-Lepri, R. Velleca, A. Vincenti, S. D'Elia, F. Chiodo, F. Ghinelli, A. Bertoli, A. d'Arminio Monforte, C. F. Perno, M. Moroni, and C. Balotta. 2004. Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy. AIDS 18:227-35.
Whitcomb, J. M., N. T. Parkin, C. Chappey, N. S. Hellmann, and C. J. Petropoulos. 2003. Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. J. Infect. Dis. 188:992-1000.
Winters, M. A., K. L. Coolley, P. Cheng, Y. A. Girard, H. Hamdan, L. C. Kovari, and T. C. Merigan. 2000. Genotypic, phenotypic, and modeling studies of a deletion in the beta3- beta4 region of the human immunodeficiency virus type 1 reverse transcriptase gene that is associated with resistance to nucleoside reverse transcriptase inhibitors. J. Virol. 74:10707-13.
Genotype-phenotype correlations in Stanford HIVRT&PrDB

NNRTI
Mutation	Drugs	Old Score	New Score
A98G	DLV,EFV	10	5
K101Q	ALL	10	5
K103Q	ALL	5	10
Y181V	DLV,NVP	30	60
Y181V	EFV	10	20
G190A	EFV	50	40
L234I	ALL	12	0

Relevant references:

Rhee SY, Liu T, Ravela J, Gonzales MJ and Shafer RW. 2004. Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother 48:3122-6
Genotype-phenotype correlations in Stanford HIVRT&PrDB

Interpretation for ddC is no longer provided

version 3.9, 2004-03-25

Several comments for Protease and RT positions were updated. FTC was added with scores identical to 3TC:

Mutation	Score
41L	0
44A/D	8
62V	0
65R	30
65 (Not R)	10
67del	15
67E/G/N	0
69del	15
69A/I/D/N/S	5
69ins	30
69 (Not A/I/D/N/S)	5
70RGE	0
74IV	0
75A/M/T/S	0
75I	4
77L	4
100I	0
115F	0
116Y	4
118I	8
151L	10
151M	15
151 (Not L/M)	5
181C	0
184I/V	60
184 (Not IV)	30
210FW	0
215C/D/E/F/I/V/S/Y	0
219E/N/Q/R	0
333D/E	0

Protease
Mutation	Drugs	Old Score	New Score
48 (Not VM)	SQV	10	15
48M	APV, IDV, RTV, ATV	na	10
	LPV	na	5
	NFV	na	25
	SQV	na	40
73A	APV, IDV, NFV, RTV, SQV, LPV, ATV	na	5
82F	LPV	15	18
82I	NFV	5	10
82T	LPV	15	18
84V	LPV	10	12

NRTI
Mutation	Drugs	Old Score	New Score
41L	ABC	10	12
41L	DDC, DDI	5	10
44A/D	ABC, AZT, D4T, DDC, DDI, TDF	0	2
67N	DDC, DDI	2	5
67 (Not E/G/N)	DDC, DDI	3	5
74I/V	AZT	-10	-8
74I/V	D4T	-5	0
100I	AZT	-10	-4
100I	TDF	-5	-4
118I	ABC, AZT, D4T, DDC, DDI, TDF	0	2
181C	AZT, TDF	-5	-4
184I	AZT, TDF	-10	-8
184V	ABC	20	16
	AZT	-10	-8
	DDI	20	12
	TDF	-10	-8
210W	ABC, D4T, TDF	10	12
210W	DDC, DDI	5	10
215F/Y	DDC, DDI	10	12

NNRTI
Mutation	Drugs	Old Score	New Score
98 (Not GS)	DLV, EFV, NVP	5	0
101P	DLV, EFV, NVP	10	20
106I	DLV, EFV, NVP	5	0

Relevant references:

Molina, J. M., G. Marcelin, J. Pavie, C. Merle, M. Troccaz, G. Leleu, and V. Calvez. (2003). Didanosine (ddI) in treatment experienced HIV-infected patients: results from a randomized double-blind study. (AI454-176 Jaguar) [Abstract H-447]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL.

version 3.8.1, 2003-12-15

NRTI
Mutation	Drugs	Old Score	New Score
65R	TDF	30	40

The resistance mutations were further classified; Major and Minor Resistance mutations for Protease Inhibitors, and NRTI and NNRTI Resistance Mutations for RT Inhibitors.

Relevant references:

Gallant J, Rodriguez AE, Weinberg W. (2003). Early non-response to tenofovir DF (TDF) + abacavir (ABC) and lamivudine (3TC) in a randomized trial compared to efavirenz (EFV) + ABC and 3TC: ESS30009 [Abstract 1722a].43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL.

version 3.8, 2003-10-15

Protease
Mutation	Drugs	Old Score	New Score
84V	ATV	20	25

NRTI
Mutation	Drugs	Old Score	New Score
184 (Not I/V)	AZT	-10	0
184 (Not I/V)	D4T	-5	0

NNRTI
Mutation	Drugs	Old Score	New Score
101Q	DLV, EFV, NVP	5	10
236 (Not L)	EFV, NVP	-5	0

In order to minimize the number of X amino acids being called, we updated our triplets table. We now translate a codon to X only when the amino acid mixture is greater than four, ie. now, codon YYY translates to FLPS and ANY to INST, when previously they translated to X.

version 3.7, 2003-09-16

NRTI
Mutation	Drugs	Old Score	New Score
106M	EFV	15	50

NNRTI
Mutation	Drugs	Old Score	New Score
75A/I/M/S	D4T	30	20

version 3.6, 2003-08-01

The Protease Resistance Notes page was updated; position 47 is now responsible for Intermediate Resistance to LPV, instead of Contributing to Resistance.
Many scores were updated for Protease and RT, and a new Protease drug was added, ATV.

ATV was added with the following scores:

Mutation	Score
10F/I/R/V	2
10 (Not F/I/R/V)	2
20I/M/R	2
20 (Not I/M/R)	2
24I/F	2
24 (Not I/F)	2
30N	0
30 (Not N)	0
32I	10
32 (Not I)	2
33F	3
33V/I	0
33 (Not F/V/I)	0
36I/L/V	2
36 (Not I/L/V)	2
46I/L/V	10
46 (Not I/L/V)	5
47V/A	5
47 (Not V/A)	5
48V	10
48 (Not V)	10
50V	0
50L	40
50 (Not V/L)	20
53L	5
53Y	2
53 (Not L/Y)	0
54L/M/T/S/V/A	10
54 (Not L/M/T/S/V/A)	5
63P	2
63 (Not P)	1
71T/I	2
71V	4
71 (Not T/V/I)	2
73C/S/T	5
73 (Not C/S/T)	2
77I	0
77 (Not I)	0
82A/F/S/T	20
82I	0
82 (Not A/F/I/S/T)	15
84A/V/C	20
84 (Not A/V/C)	10
88D/S/T	10
88 (Not D/S/T)	5
90M	20
90 (Not M)	20
93L	1
93 (Not L)	0

Relevant references:

version 3.5.1, 2003-07-25

Several comments were updated for Protease and RT positions.

version 3.5, 2003-07-10

Almost all comments for Protease and RT positions were updated.

Protease
Mutation	Drugs	Old Score	New Score
47V	APV	25	20
47V	LPV	5	10
47A	APV, LPV	0	20
47A	IDV, NFV, RTV, SQV	0	5
47 (Not V/A)	LPV	2	10
47 (Not V/A)	IDV, NFV, RTV, SQV	2	5
84A	APV, NFV, SQV	0	40
	IDV, RTV	0	25
	LPV	0	10
84C	APV, NFV, SQV	0	25
	IDV, RTV	0	15
	LPV	0	10

NRTI
Mutation	Drugs	Old Score	New Score
65R	D4T	0	15

NNRTI
Mutation	Drugs	Old Score	New Score
103S	DLV, NVP	30	60
103S	EFV	30	50
103T	DLV, NVP	30	60
103T	EFV	30	50
103Q	DLV, EFV, NVP	0	5

Relevant references:

version 3.4, 2003-06-09

Comments were added to the HIVDB algorithm to include RT positions 238 and 333. In addition comments for protease positions 20, 32, 46, 47, 54, 63, and 82, and RT positions 65, 74, 98, 101, 103, 151, 184, and 215 were updated.
The default font for the reports has been increased for improved readability.

version 3.3.1, 2003-05-02

Mutations at RT position 238 are now classified as resistance mutations
RT mutation V106M now has a comment describing its involvement in NNRTI resistance, and is no longer classified as an 'atypical' mutation
The default setting for the programs is now the mutation input form, rather than the sequence input form.

Relevant references:

Brenner, B, et al. (2003).

version 3.3, 2003-04-25

The programs now accept as input Visible Genetics sequencer files (GRFs)

Protease
Mutation	Drugs	Old Score	New Score
V32I	LPV	3	10
L33F/V	NFV	0	2
L33F/V	RTV	0	2
G48 (Not V)	APV, IDV, LPV, RTV	0	5
G48 (Not V)	NFV, SQV	0	10
I54L	APV	10	15
I54L	LPV	10	12
I54M	LPV	10	12

Relevant references:

Parkin, NT, et al. (2003).

version 3.2, 2003-03-04

The results of subtyping analysis by reference sequence comparison are now rounded to one decimal point, rather than the integer value.
RT mutations V179I and A98S are no longer classified as resistance mutations
V179I is no longer classified as an atypical mutation
If no sequence identifier is provided but the file uploaded feature has been used, the sequence name becomes the name of the submitted file
General comments are now sorted by position number

version 3.1, 2003-02-19

Internal Release

version 3.0, 2003-01

A local alignment progam (LAP), instead of the previous global alignment program (NAP), is now used.

A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

Sequence Analysis Programs

Table of Contents

The Team

The Data