hiv-1 reverse transcriptase thymidine analogue resistance

Poster No TUPDA 205XVII International AIDS Conference 2008

AZT/d4T, 3TC and NVP/EFV is widely available, inexpensive generic regimen in AZT/d4T, 3TC and NVP/EFV is widely available, inexpensive generic regimen in

India.India.

Monitoring patients for IF/CF in developing countries is likely to mean that Monitoring patients for IF/CF in developing countries is likely to mean that

patients will experience virological failure (VF) on thymidine analogues for a patients will experience virological failure (VF) on thymidine analogues for a

prolonged periodprolonged period

To analyze the pattern of resistant mutations among patients failing first-line To analyze the pattern of resistant mutations among patients failing first-line

HAART HAART

BACKGROUND & OBJECTIVEBACKGROUND & OBJECTIVE

Gallant JE, 2007, Sungkanuparph Gallant JE, 2007, Sungkanuparph et al.,et al., 2007 2007

MATERIALS AND METHODSMATERIALS AND METHODS

350 - IF to first-line regimens ; 326 350 - IF to first-line regimens ; 326 (AZT/d4T+3TC+NVP/EFV)(AZT/d4T+3TC+NVP/EFV)

Group A n=179 Group B n=171 Group A n=179 Group B n=171

Homebrew genotyping (Boden Homebrew genotyping (Boden et alet al., 1999 and ., 1999 and Larder Larder et alet al., 1991) ., 1991) http://hivdb.stanford.edu/hiv, , accessed on 21 January 2008.accessed on 21 January 2008.

TAM1 (41L, 210W, 215Y) and TAM2 (67N, 70R, TAM1 (41L, 210W, 215Y) and TAM2 (67N, 70R, 215F, 219E/Q)215F, 219E/Q)

Chi-square tests and student’s t-test Chi-square tests and student’s t-test

Demographics and Clinical history (n=350)

RT Resistance Mutations (n=326)

RT MutationsRT Mutations Frequency(%)Frequency(%)

K65RK65R 20 (6%)20 (6%)

L74VL74V 26 (7%)26 (7%)

T69NT69N 21 (6%)21 (6%)

T69DT69D 28 (8%)28 (8%)

TAMSTAMS 217(62%)217(62%)

Q complexQ complex 33 (9%)33 (9%)

M184VM184V 250 (71%)250 (71%)

M184IM184I 12 (3%)12 (3%)

E44DE44D 36 (10%)36 (10%)

V118IV118I 39 (11%)39 (11%)

RT MutationsRT Mutations Frequency(%)Frequency(%)

L1001L1001 9(3%)9(3%)

K103NK103N 101 (29%)101 (29%)

V106MV106M 42 (12%)42 (12%)

V106AV106A 6 (2%)6 (2%)

V108IV108I 35 (10%)35 (10%)

Y181CY181C 106 (30%)106 (30%)

Y188L/H/CY188L/H/C 35 (10%)35 (10%)

G190AG190A 92 (26%)92 (26%)

G190/E/SG190/E/S 6 (2%)6 (2%)

V179DV179D 7 (2%)7 (2%)

P225HP225H 9 (3%)9 (3%)

A98GA98G 53 (15%)53 (15%)

M230LM230L 3 (1%)3 (1%)

K101E/PK101E/P 42 (12%)42 (12%)

F227LF227L 18 (5%)18 (5%)

Selection of TAMs among patients failing first-line regimen containing thymidine analogue (n=326)

0%

5%

10%

15%

20%

25%

30%

35%

40%

Freq

uenc

y (%

)

AZT(76) D4T(103) AZT(75) D4T(72)

Group A (n=179) Group B (n=147)

Thymidine Analogues

TAM1 TAM2 MIX

Selection of TAMs pathway with respect to AZT/d4T exposure (n=326)

SUMMARY AND CONCLUSION

When thymidine analogues were used, NRTI cross resistance could be prevented by identifying early virological failure and modifying therapy, thus easier to design fully suppressive second-line regimen after treatment failure

TAMs – second most predominant (62%) next to M184V.

TAM 1 pathway was significantly (p<0.05) selected among mono/dual exposed