Background
Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up.
Objectives
We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF.
Methods
Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF.
Results
We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC.
Conclusions
In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.
Background
The arrival of highly effective, well tolerated direct-acting antiviral agents (DAA) led to a dramatic decrease in HCV prevalence. HIV-HCV coinfected patients are deemed a priority population for HCV elimination, while a rise of recently acquired HCV infections in MSM has been described. We describe the variations in HIV-HCV epidemiology in the French Dat’AIDS cohort.
Methods
Retrospective analysis of a prospective HIV-infected cohort from 2012 to 2018. Determination of HCV prevalence, incidence, proportion of viremic patients, treatment uptake and mortality rate in the full cohort and by HIV risk factors.
Results
From 2012 to 2018, 50861 HIV-infected patients with a known HCV status were followed-up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100PY to 1.25/100PY in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in IVDU (35.6%). In MSM, treatment at acute phase represented 30.0% of treatments in 2018.
Conclusions
A major shift in HCV epidemiology was observed in HIV-infected patients in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM.
With growing numbers of construction sites, aggregate supply in the Ile-de-France region (Paris and the surrounding area) will be a major issue in the coming years. This means that dialogue is needed between stakeholders to build and evaluate scenarios together for the future in this area of aggregate supply and waste reclamation. This work had the goal of describing, analysing and discussing the first evaluation of potential scenarios from the thematic and methodological standpoint, asking questions about issues of sustainable circularity in the aggregate sector in Ile-de-France. In the state of the art, tools for objective evaluation are being widely developed in the sector, whereas tools for subjective evaluation remain largely unexplored, hence this work. As results, we have given structure to what challenges will be raised for a circular economy for supplying aggregates in Ile-de-France. However, the challenges are not even for all of the issues, scenarios and impacts.
Background
Two-drug regimens based on integrase strand transfer inhibitors (INSTIs) and boosted PIs have entered recommended ART. However, INSTIs and boosted PIs may not be suitable for all patients. We aimed to report our experience with doravirine/lamivudine as maintenance therapy in people living with HIV (PLWH) followed in French HIV settings.
Methods
This observational study enrolled all adults who initiated doravirine/lamivudine between 1 September 2019 and 31 October 2021, in French HIV centres participating in the Dat’AIDS cohort. The primary outcome was the rate of virological success (plasma HIV-RNA < 50 copies/mL) at Week (W)48. Secondary outcomes included: rate of treatment discontinuation for non-virological reasons, evolution of CD4 count and CD4/CD8 ratio over follow-up.
Results
Fifty patients were included, with 34 (68%) men; median age: 58 years (IQR 51–62), ART duration: 20 years (13–23), duration of virological suppression: 14 years (8–19), CD4 count: 784 cells/mm3 (636–889). Prior to switching, all had plasma HIV-RNA < 50 copies/mL. All but three were naive to doravirine, and 36 (72%) came from a three-drug regimen. Median follow-up was 79 weeks (IQR 60–96). Virological success rate at W48 was 98.0% (95% CI 89.4–99.9). One virological failure occurred at W18 (HIV-RNA = 101 copies/mL) in a patient who briefly discontinued doravirine/lamivudine due to intense nightmares; there was no resistance at baseline and no resistance emergence. There were three strategy discontinuations for adverse events (digestive disorders: n = 2; insomnia: n = 1). There was no significant change in CD4/CD8 ratio, while CD4 T cell count significantly increased.
Conclusions
These preliminary findings suggest that doravirine/lamivudine regimens can maintain high levels of viral suppression in highly ART-experienced PLWH with long-term viral suppression, and good CD4+ T cell count.
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