International Scholarly Research Notices

Review Article

HIV-1 Genetic Variability and Clinical Implications

Table 1

Main drug resistance mutations observed in different HIV-1 subtypes.


Drug class	Subtype	Polymorphisms or mutations or positions associated with drug resistance	Drug(s) related	Comments	References

Reverse transcriptase

	C	K65R	d4T, ddI, ABC, TDF	Preferential selection	[14, 15, 148–152, 215, 216]
NRTI	C	K70E	d4T, ddI, AZT	High prevalence in subtype C endemic area	[153]
	B	D67N	d4T, AZT	Preferential selection	[148, 149, 151]

	G	A98S	NNRTIs	Common polymorphism	[15, 173]
	B, C, F, CRF02_AG	K103N	EFV, DLV, NPV	Lower frequency in subtype C compared to B, F, and AG subtype	[76, 168, 169, 172]
	B, C	V106M	EFV, NVP	Lower genetic barrier in subtype C in comparison with subtype B	[140, 141, 171]
NNRTI	C	E138K	ETR	Preferential selection under drug pressure in subtype C	[177, 178]
	C	G190A	NNRTIs	High frequency in subtype C	[140]
	A, B	Y181C	ETR	Preferential selection under drug pressure on A and B subtypes	[178]
	C	Y181C, Y188L	EFV, DLV, NPV	Higher frequency in subtype C	[76, 168, 169, 172]
	C	N348I	ETR	Higher frequency in subtype C at etravirine failure	[179, 180]

Protease

	CRF02_AG	G17E, I64M	NFV, ATV, IDV	Hypersusceptibility in CRF02_AG	[193]
	B, C, F, G, CRF01_AE	D30N	NFV	Lower prevalence in C, F, G, and CRF01_AE subtypes under NFV pressure compared to subtype B	[186, 187]
	Non-B	M36I	PIs	Natural polymorphism	[133, 139, 191]
PI	A, C, D, F, G, CRF02_AG	10, 13, 14, 20, 53, 63, 67, 73, 74, 77, 82, 88, 89	PIs	Natural polymorphisms	[87, 132, 133, 142–145, 194]
	A, C, F, CRF01_AE	L89M	ATV, LPV, NFV	Natural polymorphism that may lead to the L89T mutational pathway	[139, 192, 224]
	CRF02_AG	L89V	FPV, DRV, LPV	Higher prevalence in CRFF02_AG compared to subtype B	[76, 143]
	B, C, F, G, CRF01_AE, CRF02_AG	N88S, L90M	ATV, NFV	Higher prevalence in C, F, G, CRF01_AE, and CRF02_AG subtypes compared to subtype B	[186, 187, 194]
	C	T74P	TPV	Higher prevalence in subtype C in comparison to subtype B	[76]
	Non-B	V82A/M/F/S	PIs	High prevalence in some non-B subtypes at failure	[194]

Integrase

	B, C	N155H, E92Q	RAL, EVG	>10-fold resistance in subtype B in comparison to subtype C	[201]
	Non-B	T97A, V151I, G163R	RAL	High frequency in non-B subtypes endemic area	[203, 204]
INI	Non-B	L101I, T124A	DTG	Higher frequency in non-B subtypes in comparison to subtype B	[198]
INI	C, CRF02_AG	G118R	RAL	Emerging at RAL failure in subtype CRF02_AG	[202]
	B	R263K	DTG	Preferential selection under drug pressure	[206]

Env gene

FI	C	N42S, L54M, A67T	T20	Higher frequency in subtype C in comparison to B	[211]
CCR5 inhibitors	C	R315Q, A316T	MVC, VCV	Higher frequency in subtype C in comparison to B	[211]

ABC: abacavir; ATV: atazanavir; AZT: zidovudine; d4T: stavudine; ddI: didanosine; DRV: darunavir; DTG: dolutegravir; ETR: etravirine; EFV: efavirenz; EVG: elvitegravir; FI: fusion inhibitor; FPV: fosamprenavir; INI: integrase inhibitor; LPV: lopinavir; MVC: maraviroc; NFV: nelfinavir; NRTI: nucleotide reverse transcriptase inhibitor; NNRTI: non-NRTI; NVP: nevirapine; PI: protease inhibitor; RAL: raltegravir; TDF: tenofovir; T20: enfuvirtide; VCV: vicriviroc.