The evolution of HIV-1 reverse transcriptase in route to acquisition of Q151M multi-drug resistance is complex and involves mutations in multiple domains

Table 1 The sequential acquisition of Q151M MDR mutations and the frequency of other RT mutations linked to MDR mutations, in patient P66.

Type or Location of mutations	Wild-type residue^a	Genetic linkage of other mutations to Q151M MDR
		4 months (636)^b		17 months (51,000)	37 months (108,769)
		n = 5^c	n = 1	n = 33	n = 31
	A62	V		V	V
Q151M MDR	V75			I	I
	Q151				M
	T69			N⁴⁵	N¹⁰⁰
Other NRTI	M184	I⁸⁰V^20d	I¹⁰⁰	V¹⁰⁰	V¹⁰⁰
	L210			S⁶F³	F⁸⁷
	V90	I²⁰		I³
	E138	A¹⁰⁰	A¹⁰⁰	A¹⁰⁰	A¹⁰⁰
NNRTI	Y181	I¹⁰⁰	I¹⁰⁰	I¹⁰⁰	I¹⁰⁰
	H221			Y⁷⁰	Y¹⁰⁰
	M230		L¹⁰⁰
	N348	I¹⁰⁰	I¹⁰⁰	I³
	I31			L⁹⁴	L¹⁰⁰
	A33				V⁹⁷
	T48				S¹⁰⁰
	S68				G¹⁰⁰
	K102				R⁶¹
	S123				N¹⁰⁰
Other DNA pol domain	I135	V⁸⁰		L⁵⁸V¹⁸T¹⁵	T¹⁰⁰
	R174			K¹⁸	K⁹⁷
	K197				E⁸⁷
	V202			I⁹¹	I¹⁰⁰
	E203			D³	D¹⁰⁰
	V314				I²⁶
	M357			R¹⁸L³
	A371				T²³
	T386			I⁹	I¹⁰⁰
Other connection subdomain	E399			D⁵⁸	D¹⁰⁰
	A403	T²⁰		T⁴⁵	T⁹⁷
	I458	V²⁰	V¹⁰⁰	V²⁴	V⁸⁴
	E471			D³⁹	D⁹⁷
RNase H domain	L517	I⁶⁰	I¹⁰⁰	I⁵⁶	I⁹⁴

^a Wild-type residue was determined based on 4-month sequences and frequency in treatment-naïve individuals as determined using Stanford University HIV database
^b Viral load in copies/mL
^c Number of single genomes linked or unlinked to Q151M MDR mutations
^d Percent of single genomes with that particular mutation calculated as follows: number of mutations per codon/number of single genomes linked or unlinked to Q151M MDR (n) × 100%

ISSN: 1742-4690