Does the M184V resistance mutation in reverse transcriptase reduce HIV transmission
2011
The study appearing in this issue by Buckton et al .( 4) also showed a lower rate of viruses harbouring the M184V mutation (0.6%) compared with K103N (6.1%) when the authors used standard genotyping methods. When they used a technique that detects minor populations, however, the rate was 7.9% for M184V and 7.3% for K103N. Their study showed that the minor population technique significantly increased the rate of detection of the M184V mutation. Other studies have also demonstrated high rates of M184V using minor population techniques in naive patients. A study from Germany showed a rate of 10.2% for K103N and a rate of 12.2% for M184V (5). The group from Montreal explored the presence of K103N and M184V minority species among 30 PHIs lacking this mutation using the standard genotyping method. Viral minority species were found in three (10%) patients with K103N and four (11%) patients with M184V (6). Those studies revealed that these mutations can be detected in similar proportions in naive patients, despite the impact of M184V on HIV fitness, suggesting that transmission of this mutation takes place at a higher frequency than suggested by the results of conventional sequencing methods. Do the later studies satisfactorily demonstrate that there is no diminution of virus transmission with M184V mutations? How compatible is this conclusion with the facts that patients with lower VL are less likely to transmit HIV and that M184V has been shown to lower VL? We are unaware of any existing animal models that can ade- quately exemplify the transmission of DRMs. The above- mentioned studies clearly show that the new techniques for detecting resistance are more sensitive for mutations that confer lower fitness, such as M184V. The role of these mutations in the process of transmission is, however, still a matter of debate.
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