HIV1 resupression on a firstline regimen despite the prescence of phenotypic drug resistance

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dc.citation.doi10.1371/JOURNAL.PONE0234937
dc.citation.epage15
dc.citation.spage1
dc.contributor.authorAdriaan Basson
dc.contributor.authorSalome Charalambous
dc.contributor.authorChristopher Hoffmann
dc.contributor.authorLynn Morris
dc.date.accessioned2023-04-17T13:42:47Z
dc.date.available2023-04-17T13:42:47Z
dc.departmentForensic Medicine and Pathology
dc.description.abstractWe have previously reported on HIV-1 infected patients who fail anti-retroviral therapy but manage to re-suppress without a regimen change despite harbouring major drug resistance mutations. Here we explore phenotypic drug resistance in such patients in order to better understand this phenomenon. Patients (n = 71) failing a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, but who subsequently re-suppressed on the same regimen, were assessed for HIV-1 genotypic drug resistance through Sanger sequencing. A subset (n =23) of these samples, as well as genotypically matched samples from patients who did not re-suppress (n = 19), were further assessed for phenotypic drug resistance in an in vitro single cycle assay. Half of the patients (n = 36/71, 51%) harboured genotypic drug resistance, with M184V(n=18/36,50%)andK103N(n=16/36,44%)being the most prevalent mutations. No significant difference in the median time to re-suppression (31–39 weeks) were observed for either group (p = 0.41). However, re-suppressors with mutant virus rebounded significantly earlier than those with wild-type virus (16 vs. 33 weeks; p = 0.014). Similar phenotypic drug resistance profiles were observed between patients who re-suppressed and patients who failed to re-suppress. While most remained susceptible to stavudine (d4T) and zidovudine (AZT), both groups showed a reduced susceptibility to 3TC and NNRTIs. HIV- 1 infected patients on an NNRTI-based regimen can achieve viral re-suppression on the same regimen despite harbouring viruses with genotypic and phenotypic drug resistance. However, re-suppression was less durable in those with resistance, reinforcing the importance of appropriate regimen choices, ongoing viral load monitoring and adherence counselling.
dc.facultyFaculty of Health Sciences
dc.identifier.citationBasson AE, Charalambous S, Hoffmann CJ, Morris L (2020) HIV-1 re-suppression on a first-line regimen despite the presence of phenotypic drug resistance. PLoS ONE 15(6): e0234937. https://doi.org/10.1371/journal.pone.0234937
dc.identifier.issn1932-6203 (online)
dc.identifier.urihttps://hdl.handle.net/10539/35232
dc.journal.titlePLoS ONE
dc.journal.volume15
dc.publisherPublic Library of Science
dc.schoolSchool of Pathology
dc.subject.otherSDG-3: Good health and well-being
dc.titleHIV1 resupression on a firstline regimen despite the prescence of phenotypic drug resistance
dc.typeArticle
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