Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase

Retrovirology

Table 2 Association of 40F and 43E with thymidine analogue-associated mutations

pos1	pos2	phi	OR	% pos2 in pos1	P value
40F	43E	0.287	38.2	84%	<10E-09
40F	41L	0.125	6.9	99%	<10E-09
40F	210W	0.162	11.2	97%	<10E-09
40F	215Y	0.124	7.2	94%	<10E-09
40F	67N	0.107	6.6	79%	<10E-09
40F	70R	0.001	1.1	9%	NS
40F	215F	-0.001	0.9	4%	NS
40F	219E	0.032	4.6	14%	<10E-09
40F	219Q	-0.003	0.8	4%	NS
43E	40F	0.287	38.2	10%	<10E-09
43E	41L	0.326	6.3	91%	<10E-09
43E	210W	0.367	9.0	78%	<10E-09
43E	215Y	0.31	6.4	82%	<10E-09
43E	67N	0.211	4.8	58%	<10E-09
43E	70R	-0.002	0.9	9%	NS
43E	215F	0.014	1.4	7%	9.7E-08
43E	219E	0.009	1.4	4%	NS
43E	219Q	0.004	1.1	6%	NS

Binomial correlation coefficients (phi) and Odds Ratios (OR) were calculated for 57 amino acid substitutions at 34 reverse transcriptase codons to study the association of E40F and K43E with each other and with known thymidine analogue associated mutations.
Phi: binomial correlation coefficient (1.0 = perfect pairwise correlation). OR: Odds Ratio – the observed frequency of the pair divided by the product of the individual mutation frequencies. P-value: chisquare probability was evaluated for significance at a Benjamini-Hochberg false discovery rate (FDR) of 0.01 for 1,566 multiple comparisons.
NS: Not significant at FDR 0.01.
Sequences with a phi value of 0.15 or greater, an odds ratio of > 2 and FDR of 0.01 were considered to be co-varying.

ISSN: 1742-4690