Plasma samples collected from each patient at four or five time points between 1991 and 1998 were genotyped. The antiretroviral treatment histories and RT and protease mutations are shown in Tables and .
Antiretroviral treatments and reverse transcriptase (RT) and protease mutations of an HIV-1-infected couple (patients A and B)
Antiretroviral treatments and reverse transcriptase (RT) and protease mutations of an HIV-1-infected couple (patients D and E)
shows the neighbor-joining tree constructed from combined protease and RT sequences using the HKY85 + Γ nucleotide substitution model. Bootstrap values are provided for the most recent common ancestor (MRCA) of each transmission pair and the more recent sequences from each patient within the pair. Maximum likelihood and maximum parsimony trees constructed from complete sequences and sequences lacking positions associated with the development of drug resistance had branching patterns identical to those of the neighbor-joining tree.
FIG. 1 Neighbor-joining tree constructed from a combination of the reverse transcriptase and protease genes using the HKY85 nucleotide substitution model with a gamma distribution (HKY85 + Γ). Gray boxes highlight sequences from the HIV-1-infected couples. (more ...)
The sequences obtained from patient D in July 1991 were closest to the MRCA for the sequences from patients D and E, consistent with the history that the virus was transmitted from patient D to patient E at about that time. The bootstrap value at the MRCA node of patients D and E was 98.
The sequence obtained from patient A in January 1992 was closest to the MRCA for the sequences from patients A and B, consistent with the transmission of virus from patient A to patient B at about that time. However, the bootstrap value at the MRCA node for patients A and B was only 42. The genetic distance between the sequences from patients A and B at their initial time points was also higher than expected (2.9%, RT; 0.35%, protease).
Because of the high genetic distance between the initial RT sequences from patients A and B and because of the low bootstrap value at the their MRCA node, we constructed neighbor-joining, maximum likelihood, and maximum parsimony trees using RT sequences from the two patients and an additional 316 subtype B control sequences from GenBank, for a total 339 control sequences (including the 23 initial control sequences). In these trees, one of the original control sequences (ASRU007) and two of the 316 control sequences were found to share an MRCA node with patient B but not with patient A. ASRU007 was isolated in the United Kingdom in 1997, AJ006287 was isolated in Spain in 1989, and L07243 was isolated in Germany some time prior to 1992. A maximum likelihood tree constructed with the RT sequences from patients A and B and the three control sequences is shown in . A plot of the distance of each control sequence to the baseline sequences from patients A and B using the HKY85 nucleotide substitution model is shown in .
FIG. 2 (A) Maximum likelihood tree constructed from the reverse transcriptase sequences from patients A and B and three epidemiologically unrelated sequences that share a common ancestor with patient B sequences but not with patient A sequences. ASRU007 was (more ...)