Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors

Scutari, Rossana; Alteri, Claudia; Vicenti, Ilaria; Carlo, Domenico Di; Zuccaro, Valentina; Incardona, Francesca; Borghi, Vanni; Bezenchek, Antonia; Andreoni, Massimo; Antinori, Andrea; Perno, Carlo Federico; Luca, Andrea De; Zazzi, Maurizio; Santoro, Maria Mercedes

doi:10.1016/j.jgar.2019.07.015

Cited by 14 publications

(18 citation statements)

References 35 publications

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“…We found a very low frequency of patients who had integrase mutations at important residues, as identi ed elsewhere, N155H have shown to be the primary/major pathways that induce resistance to Raltegravir, this could be particularly important when using Raltegravir as it has been shown that only one mutation was su cient to observe virologic failure in highly experienced patients [45,46]. This substitution also reduces Elvitegravir susceptibility but does not, alone, compromise Dolutegravir nor Bictegravir by itself [47,48]. We did not nd an explanation to the greater, but not signi cant, proportion of patients with treatment interruption in Raltegravir group before and after PS matching.…”

Section: Resultssupporting

confidence: 62%

Outcomes of Heavily Experienced HIV-infected Patients Receiving Salvage Raltegravir-based Therapy

Escarcina¹,

Netto²,

Brites³

2021

Preprint

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Background: New antiretrovirals improved the treatment success for heavily experienced HIV-infected patients as treatment failures or resistance to ART may limit the options for further therapy. Nonetheless, construction of ‘salvage’ regimens remains a complex and challenging issue worldwide. This study assessed real-life virologic success, long-term survival and adverse events in treatment experienced patients initiating either Raltegravir or other drugs for salvage regimens.Methods: we conducted a retrospective cohort study on adults with treatment failure (HIV-1 RNA viral load [PVL] >1000 copies/mL) who started either Raltegravir or other drugs (Darunavir/Ritonavir, Maraviroc or Etravirine). Propensity score (PS) matching methods were used to account for baseline clinical differences. We used Kaplan-Meier method and Generalized Wilcoxon tests for the matched subset to evaluate probability of virologic suppression (PVL<50 copies/mL) during follow up. Comparison of Mortality rates, cases of toxicity, treatment interruption, virologic failure and loss of follow-up, were ascertained using Poisson regression.Results: 168 patients (123 on Raltegravir; 45 on other drugs). Of these, 90 patients were matched by PS, 45 patients from each group, equivalent to 98 person-years of follow-up. During follow-up, virologic suppression was similar for both regimens (77.8% vs 82.2%, p=0.73). During a mean follow-up of 1.09 (SD = 0.32) years rates of mortality (4.04 vs 6.18 persons per 100 person-years; p=0.67), drug toxicity (0.00 vs 2.06 persons per 100 person-years; p=0.49), treatment interruption (8.07 vs 0.00 persons per 100 person-years; p=0.06), virologic failure (2.02 vs 4.12 persons per 100 person-years; p=0.61) and loss of follow-up (6.05 vs 4.12 persons per 100 person-years; p=0.70) did not differ between Raltegravir and other salvage regimens recipients.Conclusion: Similar survival and virologic success rates were found for Raltegravir and other drugs for salvage regimens, with similar rates of drug toxicity, treatment interruption, virologic failure and loss of follow-up.

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Section: Resultssupporting

confidence: 62%

Outcomes of Heavily Experienced HIV-infected Patients Receiving Salvage Raltegravir-based Therapy

Escarcina¹,

Netto²,

Brites³

2021

Preprint

View full text Add to dashboard Cite

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“…The rapid virological suppression associated with INSTIs is of utmost importance to prevent HIV transmission [7]. There appears to be limited circulation of INSTI-resistant strains; however, drug resistance may emerge at virological failure of any antiretroviral, leading to reduced treatment options for future ART approaches [16,17]. Selection of drug resistance mutations depends on different factors, including adherence to therapy, forgiveness and genetic barrier of the ART regimen [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of integrase strand transfer inhibitors in HIV‐infected treatment‐experienced individuals across Europe

et al. 2022

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“…This may be particularly important, as it has been shown that only one mutation is su cient to observe virologic failure in highly experienced patients [45,46]. This substitution also reduces susceptibility to elvitegravir but does not affect dolutegravir nor bictegravir alone [47,48]. We found no explanation for the larger, but non-signi cant proportion of patients with treatment interruption in the raltegravir group before and after PS matching.…”

Section: Discussionmentioning

confidence: 64%

Outcomes of Heavily Experienced HIV-Infected Patients Receiving Salvage Raltegravir-Based Therapy

Escarcina

Netto

Brites

2022

Preprint

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Objectives To assess real-life virologic success, long-term survival, and adverse events in treatment-experienced patients initiating either raltegravir or other third-line drugs (darunavir/ritonavir, maraviroc or etravirine) for salvage regimens in a Brazilian cohort of heavily treated patients. Results We included 168 patients initiating salvage regimens, 123 on raltegravir and 45 on other drugs (darunavir/ritonavir, maraviroc or etravirine). Of these, 90 patients were matched by Propensity score (PS) methods to account for clinical differences at the time of the switch from failing ART regimens, 45 patients from each group. During follow-up, virologic suppression (PVL<50 copies/mL) was similar for both groups (77.8% vs. 82.2%, p=0.73). During a mean follow-up of 1.09 (SD = 0.32) years, mortality rates (4.04 vs 6.18 persons per 100 person-years; p=0.67), drug toxicity (0.00 vs 2.06 persons per 100 person-years; p=0.49), treatment interruption (8.07 vs 0.00 persons per 100 person-years; p=0.06), virologic failure (2.02 vs 4.12 persons per 100 person-years; p=0.61) and loss of follow-up (6.05 vs 4.12 persons per 100 person-years; p=0.70) were similar for both groups. Our findings suggest similar survival and virologic success rates for raltegravir and other drugs for salvage regimens, with similar drug toxicity rates, treatment interruption, virologic failure, and loss of follow-up.

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Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors

Cited by 14 publications

References 35 publications

Outcomes of Heavily Experienced HIV-infected Patients Receiving Salvage Raltegravir-based Therapy

Outcomes of Heavily Experienced HIV-infected Patients Receiving Salvage Raltegravir-based Therapy

Effectiveness of integrase strand transfer inhibitors in HIV‐infected treatment‐experienced individuals across Europe

Outcomes of Heavily Experienced HIV-Infected Patients Receiving Salvage Raltegravir-Based Therapy

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