Divergence of HIV-1 Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection populations for the duration of cART could end result both from on-going cycles of replication major to the emergence of new variants or as a consequence of shifts in the viral variants Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection existing in the plasma in the course of suppression, indicating a dynamic reservoir. To investigate the possibility of populace change (divergence) throughout cART, we used a test for panmixia to detect modifications in the inhabitants composition throughout therapy in contrast to pretherapy virus. The panmixia take a look at compares populations of one-genome sequences obtained from longitudinal samples and offers a p-benefit for the probability that the populations are the exact same . Chances of <10ÃÂ¢ÃÂÃÂ3 were considered to indicate significantly different populations, taking into account the large numbers of comparisons. Figure 3 and Table 3 show the panmixia results for single-genome sequences from group 1 (Figure 3a, Table 3), group 2, (Figure 3b, Table 3), and group 3 (Figure 3c, Table 3) compared to pretherapy sequences. Panmixia probabilities of virus populations in samples collected from patients on cART compared to pre-therapy populations did not achieve significance (Figure 3a) in 8/10 patients from group 1. These results indicate that there is typically no significant shift in the plasma virus population during the first and second phases of decay after initiating cART despite up to 10,000-fold declines in levels of viremia. Two patients in group 1 (PID 6, 7), however, did show a significant change in population structure after 173 and 193 days on therapy. Additional analyses describing the nature of these changes are presented below. Three of 5 patients in group 2 (long-term cART) showed a significant change in population structure during cART for 4ÃÂ¢ÃÂÃÂ12 years with no treatment interruptions, suggesting either that new variants emerged during therapy or that the reservoir for persistent viremia is dynamic. Four of 5 patients in group 3 (long-term cART but with brief treatment interruptions) showed a significant shift in population structure using the panmixia test. The results from group 2 and 3 show that, although plasma HIV-1 populations do not typically change in the early phases of viral decay, shifts in virus populations (without a change in overall diversity) are readily detectable after long-term therapy and in rebound viremia. They imply that either a compartment allowing on-going cycles of replication exists during cART or subsets of infected cells expressing virus particles shift over the course of treatment (through proliferation and/or death).
To specifically investigate whether prolonged HIV-1 suppression resulted in changes in amino acid sequences, we investigated nonsynonymous changes alone in patients from groups 1 and 2 for which there were more than 7 sequences at time points with <50 copies/ml (NÃÂ¢ÃÂÃÂ=ÃÂ¢ÃÂÃÂ8) (Table S2). We found that amino acid frequencies were remarkably stable during cART. In fact, virus populations in 4/8 patients had no significant change at any of the PR or RT loci. As all enrolled patients underwent HLA testing, we were able to investigate, using in silico techniques, the predicted positions of all the CTL epitopes in the HIV-1 sequence as well as the estimated binding affinity of all the HIV-1 peptides at each epitope site .