Abstract
We 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%) and K103N (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.
Highlights
The use of antiretroviral therapy (ART) has a significant impact on the control of HIV-1 infection and HIV associated morbidity [1]
It is not uncommon for patients on ART that experience virological failure to re-suppress on the same regimen despite the presence of major drug resistance mutations that accumulated during sub-optimal ART
We examined the impact of drug resistance mutations on the phenotypic response to ARVs in such patients from a workplace HIV programme that was initiated before roll-out of the national ARV treatment program in South Africa [13]
Summary
The use of antiretroviral therapy (ART) has a significant impact on the control of HIV-1 infection and HIV associated morbidity [1]. The South African national guidelines for the management of HIV infection promote viral load testing for monitoring viral suppression on ART, as well as for diagnosing treatment failure [4]. Re-suppression has been observed in patients with major genotypic drug resistance mutations those failing an NNRTI-based first-line regimen with M184V and K103N [7, 11, 13, 15]. The presence of such genotypic drug resistance mutations is usually associated with a decrease in the effectiveness of ART. We report on the genotypic resistance profiles of patients who re-suppressed on the same regimen, and performed in vitro phenotypic resistance testing to evaluate genotypic drug resistance in the context of re-suppression and failure
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