Skip to main content
editorial
. 2015 Aug 12;4(3):169–177. doi: 10.5501/wjv.v4.i3.169

Table 1.

Summary of most relevant genetic determinants of antiretroviral drug pharmacokinetics and toxicity

Drug/drug class Gene, allele(s)/SNPs SNP Reported associations Additional observations Ref.
Abacavir HLA-B*5701 2395029 ↑ risk of HSR Cost effective test and included in all ART guidelines [11-13]
Tenofovir ABCC2 (MRP2)1249G > A 2273697 ↑ risk of renal proximal tubulopathy in French populations To be confirmed in other populations [14,15]
Lamivudine, Zidovudine ABCC4 (MRP4) 3724G > A, 4131T > G 22736973742106 ↑ intracellular exposure of stavudine triphosphate Uncertain clinical significance [15,53]
NRTIs TNFα238G > A 361525 Earlier onset of lipoatrophy Negative findings reported by others [16-20]
Stavudine, NRTIs IL1β + 3954C > T 1143634 ↓ risk of lipodystrophy in Spanish populations To be confirmed in other populations [20]
NRTIs MMP1-16071G > 2G 1799750 ↑ risk of lipodystrophy in Spanish populations To be confirmed in other populations [21]
Stavudine, Zidovudine TS ↓ expression and MTHFR 1298 A > C ↑ activity genotypes 1801131 ↑ risk of lipodystrophy and peripheral neuropathy in Spanish populations To be confirmed in other populations [24,25]
NRTIs LPS-binding protein (LBP) T > C 2232582 ↑ risk of lipodystrophy in Spanish population To be confirmed in other populations [22]
NRTIs Mitochondrial DNA (haplogroup T): MTND1*LHON4216C, MTND2*LHON4917G, 7028C > T, 10398G > A, 13368G > A 28357980 ↑ risk of peripheral neuropathy Tissue specific mitochondrial DNA depletion may also play some role in NRTI toxicity [7,26,27]
NRTIs HFE845G > A ↓ risk of peripheral neuropathy Negative findings reported by others [28,29]
NRTIs CFTR 1717-1G > A, IVS8 5T, SPINK-1 112C > T ↑ risk of pancreatitis Reported also in the general population [30]
Nevirapine HLA-DRB1*0101 ↑ risk of HSR and hepatotoxicity CD4 cell % > 25% associated with ↑ risk [31,32]
Nevirapine HLA-cw8 ↑ risk of HSR in Italian and Japanese populations [33,34]
Nevirapine CYP2B6 983T > C 28399499 ↑ risk of HSR in Malawian and Ugandan populations Stevens-Johnson syndrome or toxic epidermal necrolysis, but no other HSR [37]
Nevirapine, Efavirenz ABCB1 (MDR1) 3435C > T 1045642 ↓ risk of hepatotoxicity [35,36]
Efavirenz ABCB1(MDR1) 3435C > T 1045642 ↓ plasma exposure Negative findings reported by some authors [51-53]
Efavirenz CYP2B6 *1/*1 haplotype ↓ plasma concentrations In patients receiving antituberculosis treatment [45]
Efavirenz ABCB1 (MDR1 3435C > T 1045642 ↑ HDL-cholesterol in Spanish populations To be confirmed in other populations [60]
Efavirenz CYP2B6 516G > T, 983T > C 3745274 28399499 ↑ plasma exposure and ↑ risk of CNS side effects Reports of successful efavirenz dose individualization [39,42,44,46,48,49]
Efavirenz CYP2A6 48T > G, UGT2B7 735A > G 2839943328365062 ↑ plasma concentrations in Black and White, but not in Hispanic individuals from the United States To be confirmed in other populations [47]
Efavirenz, Nevirapine CYP2B6 516G > T, 983T > C 28399499 ↑ plasma exposure in African populations To be confirmed in other populations [43]
NNRTIs ABCA1/Hepatic Lipase (LIPC)/Cholesteryl Ester Transfer Protein (CETP) 41493131735393764261 ↑ LDL-cholesterol in Spanish populations To be confirmed in other populations [61]
PIs ABCA1 2962A > G ↑ risk of hyperlipidemia [60]
PIs CETP 279A > G ↑ risk of hyperlipidemia [60]
PIs APOA5-1131T > C, 64G > C 662799 ↑ risk of hyperlipidemia [60,62]
Antiretrovirals APOE/LDL Receptor (LDLR) 4055092228671 ↑ risk of trunk fat gain in Spanish populations To be confirmed in other populations [23]
PIs APOC3 482 C > T, 455 C > T, 3238 C > G 285411728541165128 ↑ risk of hyperlipidemia [18,63]
PIs APOE ε2 and ε3 haplotypes ↑ risk of hyperlipidemia [18]
Antiretrovirals Insulin Receptor Substrate 1 (IRS1) 1801278 ↑ risk of limbs lipoatrophy in Spanish populations To be confirmed in other populations [23]
Raltegravir UGT1A1*28/*28 ↑ modestly plasma levels Clinically no significant [57]
Atazanavir, Indinavir UGT1A1*28 Unconjugated hyperbilirubinemia and jaundice [54,55]
Atazanavir ABCB1 (MDR1) 3435C > T 1045642 Unconjugated hyperbilirubinemia and jaundice ↑ plasma levels [57]
Atazanavir ABCB1 (MDR1) 2677 G > T 2032582 ↑ intracellular/plasma concentration ratios For GG homozygous as compared with GT and TT genotypes [58]
Nelfinavir CYP2C19*2 (681G > A) 4244285 ↑ drug exposure in Italian and multiracial Americans To be confirmed in other populations [39]
Indinavir CYP3A5*3 (A6986G) ↑ oral clearance To be confirmed in other populations [53]
Maraviroc CCR5WT/Δ32 No effect on virologic response Clinically not significant [7]

SNP: Single-nucleotide polymorphisms; HSR: Hypersensitive reaction; ART: Antiretroviral therapy; CNS: Central nervous system; NRTIs: Nucleoside reverse transcriptase inhibitors; NNRTIs: Non-nucleoside reverse transcriptase inhibitors; PIs: Protease inhibitors.