Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana

Medicine (Baltimore)

Individuals living with human immunodeficiency virus (HIV) who don’t respond well to antiretroviral medication may have had a virus that has changed its structural characteristics from its original form. These changed viruses may exist as high- or low-level viruses. Sanger sequencing is the widely used method that can be used to test the changed viruses that is present at higher levels. However, Sanger sequencing is unable to test viruses that are present at low levels. There is no information on viruses present at low levels among HIV-positive individuals in Botswana who had never been received HIV treatment. We used next-generation sequencing method to see how many individuals had viruses that had changed its structure. In 33 out of the 103 people had low level viruses that altered its structure of which four people also had high level viruses that altered its structure. Of the 103 individuals, 82 had follow-up information on how the virus was progressing while on HIV treatment. The HIV treatment was not effective for 12 of 82 individuals. Four people with ineffective HIV treatment showed K65R, K103N, V108I, and Y188C altered viruses at low levels. There was no difference in the number of altered viruses in people who responded well to treatment and those who did not. However, people with viruses that had low level altered HIV viruses towards reverse transcriptase treatment had a higher chance of failing treatment. Next-generation sequencing was able to detect low level altered viruses in this cohort in Botswana, but these viruses did not contribute significantly to treatment failure. Future studies will need to focus on the role of altered viruses existing at low levels in DTG-based first- line treatment and to determine the prevalence of low-frequency linked dual-class resistance mutations, which have been reported to be more associated with treatment failure.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.