Pharmacogenetics as a tool to tailor antiretroviral therapy: A review

Table 1 Pharmacogenetics and highly active antiretroviral therapy toxicity

ARVs	Polymorphisms	Effects
NRTIs
Abacavir (ABC)	HLA-B*5701	Hypersensitivity Reaction Syndrome
Tenofovir (TDF)	ABCC2-MRP2 (1249G > A)	Increased risk of tubulopathy
Lamivudine (3TC)	MRP4 4131T > G	Increased plasma concentrations
Zidovudine (AZT)	MRP4 3724 G > A	Increased plasma concentrations
Didanosine (ddI)	CFTR 1717-1G > A,	Higher risk of pancreatitis
	IV585T,
Didanosine (ddI), Zalcitabine (ddC), Stavudine (d4T)	SPINK-1 112C > T	Leber’s Hereditary Optic Neuropathy, Peripheral Neuropathy
	MTND1 LHON4216C,
	MTND2 LHON4917G
NNRTIs
Nevirapine (NVP)	HLA-B*58:01, *15:02, *35:05	Cutaneous rash, SJS/TEN
	ABCC10rs2125739, CYP2B6 516G > T	Increased plasma concentration, hepatotoxicity
		Reduced risk of hepatotoxicity
Efavirenz (EFV)	MDR1 3435C > T	Higher plasma concentrations, SNC side effects
	CYP2B6 G516T, T983C
PIs
Atazanavir (ATV)	UGT1A1*28, MDR1 3435C/C	Hyperbilirubinemia and jaundice
All PIs	TNF gene 238G > A	Early onset of lypodistrophy
	APOA5 (1131T > C, 64G > C),	High risk of dyslipidemia
	APOC3 (482C > T, 455C > T, 3238C > G)
	ABCA1 2962A > G
	APOE (ε2, ε3 haplotypes)
Others
Maraviroc (MVC)	SLC01B1 521T > C (rs4149056)	Increased plasma concentrations
Raltegravir (RAL)	UGT1A1*28	Increased plasma concentrations

Table 2 Pharmacogenetics and highly active antiretroviral therapy response

Polymorphisms	Drug response
CYP3A5*1	Increased PIs clearance
CYP2B6 rs3475274, rs28399499	Increased EFV and NVP plasma concentrations
ABCB1 3435C > T	Better viral responses to EFV exposure
ABCB1 rs1045642 (3435T > C)	CT/CC genotype associated with higher CD4 count in EFV, 3TC, NVP containing regimen

PIs: Protease inhibitors; NVP: Nevirapine; EFV: Efavirenz.