| |
Drug |
Gene (Protein) |
Variants (ref.) |
Genetic consequence |
Clinical impact |
Clinical relevance |
References |
| |
|
|
|
|
Efficacy |
Toxicity |
|
|
| NNRTI |
EFV |
CYP2B6 (CYP2B6) |
516C>T (rs3745274) |
Gln172His Disminished function |
Yes Higher plasma levels |
Yes CNS adverse effects |
EFV range: 1-4 µg/mL. TT genotype associated with more risk for CNS adverse effects |
[6-9,13] |
| |
|
|
785A>G (rs2279343) |
Lys262Arg Disminished function |
Yes Higher plasma levels |
Yes CNS adverse effects |
Genotype 516/983 associated with increased CNS events |
[10-14] |
| |
|
|
983T>C (rs28399499) |
Ile328Thr Decreased protein expression |
Yes Higher plasma levels |
Yes CNS adverse effects |
Genotype 516/983 associated with increased CNS events |
[11-13] |
| |
|
ABCB1 (P-gp) |
3435C>T (rs1045642) |
Ile1145Ile Synonymous substitution. In LD with ABCB1 1236 and 2677 |
Controversial influence in plasma EFV levels |
- |
Decreased likelihood of virologic failure and decreased emergence of resistant virus |
[1,17-19] |
| |
NVP |
CYP2B6 (CYP2B6) |
516C>T (rs3745274) |
Gln172His Disminished function |
Yes Higher plasma levels |
No |
- |
[23,31-33] |
| |
|
|
983T>C (rs28399499) |
Ile328Thr Decreased protein expresion |
Yes Higher plasma levels |
No |
- |
[35,36] |
| |
|
ABCB1 (P-gp) |
3435C>T (rs1045642) |
Ile1145Ile Synonymous substitution. In LD with ABCB1 1236 and 2677 |
No |
No |
T allele associated with lower risk of hepatotoxicity |
[37,39] |
| |
|
HLA-DR |
HLA-DRB1*0101 |
- |
No |
Yes HSR |
Greater risk for hypersensitivity reaction |
[24,25] |
| |
|
HLA-C |
HLA-Cw*8 |
- |
No |
Yes HSR |
Greater risk for hypersensitivity reaction. |
[26,27] |
| |
|
HLA-B |
HLA-B3505 |
- |
No |
Yes |
NVP skin rash |
[28] |
| IPs |
ATV |
UGT1A1 (UGT1A1) |
*28 (rs8175347) (rs887829) |
*280=Promoter region. (Insertion at TATA Box) |
No |
Yes Gilbert´s syndrome. Increased levels of bilirubin |
Higher risk of hyperbilirubinemia. |
[48,61-63] |
| |
|
ABCB1 (P-gp) |
3435C>T (rs1045642)
2677G>T (rs2032585) |
Ile1145Ile Synonymous substitution.
Ala893Ser |
Yes Lower ATV plasma levels. |
No |
ATV minimum effective concentration= 0.15 µg/mL. Risk of subtherapeutic levels in TT carriers. |
[47-49]
|
| |
|
NR1I2 (PXR) |
63396C>T (rs2472677) |
- |
Yes Lower ATV plasma levels |
|
Risk of subtherapeutic levels in TT carriers |
[53,54] |
| |
LPV |
SLCO1B1 (OATP1B1) |
521T>C (rs4149056) |
Val174Arg Reduced transport activity |
Yes Higher LPV plasma levels with CC genotype |
No |
- |
[64-67] |
| NRTIs |
ABC |
HLA-B HLA-B*57:01 |
NA |
- |
No |
Yes |
Abacavir Hypersensitivity Reaction (ABC-HSR) |
[72-73] |
| |
|
HLA complex P5 (HCP5) |
335T>G (rs2395029) |
Val112Gly |
No |
Yes |
Alternative marker for screening of individuals at risk for ABC-HSR |
[82-85] |
| |
TFV |
ABCC2(MRP2) |
CATC Haplotype (-24, 1249, 3563, 3972) (rs717620, rs2273697, rs8187694, rs3740066)
-24CC (rs717620) |
NA Val417Ile Val1188Glu Ile1324Ile
- |
No
No |
Yes
Yes |
CATC Haplotype associated with greater risk of KTD.
-24CCassociated with higher risk of KTD |
[99-100] |
| |
|
ABCC4(MRP4) |
3463A>G (rs1751034) |
- |
Yes Higher intracellular TFV-DP |
No |
- |
[98] |
| |
|
ABCC4 (MRP4) |
-669C>T (rs899494) |
- |
No |
Yes |
Risk for KTD |
[100] |
| |
|
ABCC10 (MRP7) |
Intron-4 (rs9349256) |
- |
No |
Yes |
Urine phosphate wasting and β2-microglobulinuria |
[100] |
| II |
RAL |
UGT1A1*28 [A(TA7)TAA] |
*28 (rs8175347) |
*280=Promoter region. (Insertion at TATA Box) |
No |
No |
- |
[109,110] |
| |
|
ABCB1 (P-gp) |
3435C>T (rs1045642) |
Ile1145Ile Synonymous substitution. |
Yes |
No |
Allele T is associated with lower RAL plasma exposure |
[113] |
