HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia

Abstract

Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.

Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome

“…Many minor/secondary INSTI RAMs (including naturally occurring integrase polymorphisms) do not compromise INSTI activity on their own [ 50 , 64 , 65 ], yet frequently arise in INSTI-treated patients [ 51 , 62 , 66 , 79 , 106 ]. The T97A integrase mutation, considered a secondary INSTI RAM in most publications, has been identified periodically in patients experiencing virologic failure on INSTI-based therapy [ 25 , 66 , 80 ] and is also an infrequent integrase polymorphism associated with low-level reduced susceptibility to EVG and/or RAL [ 45 , 50 , 86 , 87 ]. However, little is known about the impact of T97A on subsequent therapy with EVG- or RAL-containing regimens.…”

“…In rare cases, T97A has also been selected alone (i.e., in the absence of primary INSTI RAMs) by RAL [ 85 – 88 ] and EVG [ 25 , 89 ], which led us to previously consider T97A alone as a special case of primary INSTI RAM that requires additional integrase mutations ( Fig 1 ) [ 25 , 45 , 89 ]. Indeed, while T97A alone confers low-level to no effect on EVG and RAL susceptibility, respectively [ 45 , 50 ], additional integrase polymorphism(s) such as V72I, L74M, and/or G163R may serve a role to further reduce INSTI susceptibility before or during INSTI-based treatment [ 86 – 88 ]. Whether the appearance of T97A is natural or transmitted, it is currently unclear if HIV-infected patients with pre-existing T97A are at risk to delayed virologic suppression or earlier virologic failure and the development of INSTI resistance.…”

Virological response and resistance profile in HIV‐1‐infected patients starting darunavir‐containing regimens

“…Sequencing of the protease (1–99 amino acids), reverse transcriptase (1–240/335 amino acids) and integrase (for patients treated with raltegravir, 1–288 amino acids) was performed as previously described . The subtype was determined using the phylogenetic approach as previously described .…”

Very High Pre-Therapy Viral Load is a Predictor of Virological Rebound in HIV-1-Infected Patients Starting a Modern First-Line Regimen

“…We detected a considerable rate of resistance also at low-level viremia (27% at viremia 51-200 copies/mL), in line with other previous studies [22 -25], confirming that the presence of resistance at these low viremia ranges is not a rare event. In this context, considering that GRT is reliable even at low-level viremia [22][23][24][25], resistance in patients experiencing rebound, especially with high pre-cART plasma viral load, should be promptly tested after rebound regardless viremia magnitude to avoid virological failure and/or loss of treatment options related to resistance development. Indeed, resistance detected at low-level viremia has been already associated with an increased risk of virological failure [26].…”