hiv-1 reverse transcriptase thymidine analogue resistance
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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
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