Reconnaître l'expérience vécue de la maladie : la recherche «â€ˆCroiser les expériences ¼.

INTRODUCTION: The action-training research project "Crossing Experiences: Towards a Transformation of Care Action in Chronic Illness" aims to offer an introduction to narrative approaches (NA), including moments of biographical narration and moments of explanation, to a mixed audience composed of patient-peer caregivers, care professionals and family caregivers interested in intervening in therapeutic patient education (TPE) programs. OBJECTIVE: To present the initial results of the training component of this research and to identify the forms of enunciation revealing traces of the construction of an emancipatory approach to care and support relationships within the framework of TPE programs. METHODOLOGY: The NAs were presented and then applied to different stages of TPE during three days of training. Collective discussions with participants were recorded. The ex-post content analyses carried out on the basis of these discussions sought to identify what interest(s) the NAs could offer, particularly in terms of experiential knowledge. RESULTS: The design of the training, centred on ethics and a non-directive, comprehensive approach, made it possible to develop an atmosphere of confidentiality, favouring the learning and practice of the DAs involved. These were implemented at different stages of the TPE process, by both carers and patients and carer-partners, and were accompanied by the adoption of an educational stance conducive to the coconstruction of care. DISCUSSION: The results show the potential of NAs to collaborate in strengthening democracy in health through the legitimisation of experiential knowledge that emerges from lived experience. CONCLUSIONS: Training in NA based on the narration of experiences and learning acquired and their explicitation through a relationship based on respect provides avenues for collaborative work in TPE by bringing out forms of mediation, capable of grasping the dimensions of life before, during and after the disease, which are formative for people. The use of NAs is also a lever for transforming the educational process, by allowing patients and caregivers to become partners with TPE caregivers.

Dolutegravir reshapes the genetic diversity of HIV-1 reservoirs.

Objectives: Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Methods: Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5). The integrase and V3 loop regions of HIV-1 DNA isolated from PBMCs were analysed by pyrosequencing at baseline and weeks 4, 24 and 48. HIV-1 genetic diversity was calculated using Shannon entropy. Results: All individuals achieved or maintained viral suppression throughout the study. A low and stable genetic diversity of archived HIV quasispecies was observed in individuals starting treatment during acute infection. A dramatic reduction of the genetic diversity was observed at week 4 of treatment in the other individuals. In these patients and despite virological suppression, a recovery of the genetic diversity of the reservoirs was observed up to 48 weeks. Viral variants bearing dolutegravir resistance-associated substitutions at integrase position 50, 124, 230 or 263 were detected in five individuals (n = 5/20, 25%) from all groups except those who were ART-failing at baseline. None of these substitutions led to virological failure. Conclusions: These data demonstrate that the genetic diversity of the HIV-1 reservoir is reshaped following the initiation of a dolutegravir-based regimen and strongly suggest that HIV-1 can continue to replicate despite successful treatment.

Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients.

BACKGROUND: Tenofovir disoproxil fumarate is a prodrug of tenofovir diphosphate that exposes patients to renal toxicity over the long term. Tenofovir alafenamide, a new prodrug, now makes it possible to reduce toxicity, but at the cost of an alteration in lipid profile. There is currently no recommendation for follow-up of lipid profile when switching from tenofovir disoproxil fumarate to tenofovir alafenamide. OBJECTIVE: Our study aimed to evaluate the effects on renal function and lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide, and the consequences for patient management. METHODS: Demographic, clinical and biological data was recorded from a retrospective clinical cohort study in real-life, including patients who switched from tenofovir disoproxil fumarate to tenofovir alafenamide. A descriptive analysis of the study population, with a comparison of biological parameters using the paired Student t test for paired data was performed. RESULTS: From January 2016 to January 2019, a total of 103 patients were included. There was no significant difference in renal function before vs after the switch in therapy (p=0.29 for creatinine, p=0.30 for phosphoremia). We observed a change in lipid profile, with a significant increase in total cholesterol (p=0.0006), HDL cholesterol (p=0.0055) and triglycerides (p=0.0242). Four patients received lipid-lowering therapy after switching. CONCLUSION: In patients who switch from tenofovir disoproxil fumarate to tenofovir alafenamide, lipid profile is altered, and may require initiation of lipid-lowering therapy. It seems necessary to monitor lipid parameters after this switch, despite the absence of an official recommendation.

Distribution and reduction magnitude of HIV-DNA burden in CD4+ T cell subsets depend on art initiation timing.

OBJECTIVE: The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4 T-cell subsets in individuals starting successful dolutegravir-based regimens. DESIGN: Twenty-seven individuals with acute infection (AI, n = 8) or chronic infection (CI, n = 5) and patients in virological success (VS, n = 10) or virological failure (VF, n = 4) on antiretroviral therapy (ART) who initiated a dolutegravir-based regimen were enrolled (NCT02557997). METHODS: CD4 T-cells from baseline and week 48 of successful treatment were sorted into effector memory (TEM), transitional memory (TTM), central memory (TCM) and naïve (TN) cell groups for total HIV-DNA measurements by qPCR. Bayesian methods were used to estimate the posterior probability of a HIV-DNA decrease more than 0.25 log copies/10 cells at week 48. RESULTS: All patients achieved HIV-RNA suppression at 48 weeks. At baseline and week 48, the highest contributions to the HIV-DNA-infected pool from CD4 T cells were observed in TTM cells in the AI group (62.4 and 60.2%, respectively), but in TCM cells for the CI, VS and VF groups (54.6 and 59.4%, 58.2 and 62.9%, 62.4 and 67.2%), respectively. HIV-DNA burden declined in all subsets after 48 weeks of treatment in the AI (probability (Pr) > 91%), CI (Pr > 52%) and VF (Pr > 52%) groups, but only in TEM cells in the VS group (Pr = 95%). CONCLUSION: Our study showed that dolutegravir-based treatment reduced the HIV-DNA cellular burden in individuals from the AI, CI and VF groups, though the reduction levels differed between the patient subgroups. Early treated patients had the highest probability of HIV-DNA reduction. Interestingly, in the aviremic VS group, HIV-DNA reduction was limited to TEM cells.

Trends in unsafe sex and influence of viral load among patients followed since primary HIV infection, 2000-2009.

BACKGROUND: In the current context of increasing unsafe sex, HIV incidence may have evolved, depending on HIV prevalence in sexual networks and, among HIV-infected persons who practice unsafe sex, on their infectivity and partners' HIV serostatus. We examined calendar trends in sexual behaviours at risk of HIV-1 transmission (SBR) among 967 adults followed since primary HIV infection (ANRS PRIMO cohort) and relationship with current treatments and viral load. METHODS: Patients completed since 2000 self-administered questionnaires on sexual practices every 6 months. SBR with HIV-negative/unknown partners were analyzed among 155 heterosexual women, 142 heterosexual men and 670 MSM by using logistic generalized estimating equation models (6656 visits). RESULTS: During 2000-2009, the frequency of SBR did not increase significantly among women with steady partners; risk factors were a low education level and alcohol/smoking use. Among heterosexual men with steady partners, the frequency of SBR doubled since 2006; during this period, the only associated factor was combined antiretroviral treatment for at least 6 months or viral load less than 400 copies/ml. Among MSM, SBR increased gradually over time; SBR with steady partners was associated with a low education level and alcohol use. SBR was more frequent among MSM with casual partners; no association with viral load was found. CONCLUSION: In France, recent trends and risk factors in unprotected sex with HIV-negative/unknown partners differ according to sex/sexual preference. The recent increase in SBR among heterosexual men with low viral load may be related to increasing awareness of the 'treatment-as-prevention' concept. The lack of association between SBR and viral load among MSM supports use of treatment-as-prevention as part of diversified prevention strategies.

Trends in post-infection CD4 cell counts and plasma HIV-1 RNA levels in HIV-1-infected patients in France between 1997 and 2005.

OBJECTIVE: We studied trends in initial post infection CD4 cell counts and viral load values in patients diagnosed at estimated time of primary infection between 1997 and 2005 in France. POPULATION AND METHODS: We selected from the French Hospital Database on HIV infection white patients with documented dates of sexually transmitted HIV-1 infection who had a first CD4 cell count (n = 1441) or viral load assay (n = 1402) within 12 months after infection and before any antiretroviral therapy. Chronological trends in initial CD4 cell counts and viral load values were studied by using linear regression analysis. RESULTS: The initial CD4 cell count declined by an average of 5.76 cells per cubic millimeter per year [95% confidence interval (CI): -11.28 to -0.24 cells/mm3 per year] and compared with 1997 initial viral load increased significantly by a mean of 0.376 log10 copies per milliliter (95% CI: 0.044 to 0.707 log10 copies/mL) in 1999, 0.548 log10 copies per milliliter (95% CI: 0.288 to 0.808 log10 copies/mL) in 2000-2002, and 0.525 log10 copies per milliliter (95% CI: 0.267 to 0.7783 log10 copies/mL) in 2003-2005. CONCLUSION: We think that lower CD4 cell counts and higher viral loads at a given time post infection suggest a more rapid progression of the disease and therefore an increased HIV pathogenicity.

Interleukin-2 before antiretroviral therapy in patients with HIV infection: a randomized trial (ANRS 119).

BACKGROUND: Interleukin (IL)-2 increases CD4 T cell counts when combined with antiretroviral therapy (ART). Whether IL-2 alone can increase CD4 cell counts is unknown. METHODS: A total of 130 adults who had a CD4 cell count of 300-500 cells/microL (and, thus, were not eligible to receive ART) were randomized to receive either intermittent IL-2 therapy or no treatment. The primary end point was a drop in CD4 cell count to <300 cells/microL, initiation of ART, the occurrence of an AIDS-defining event, or death. RESULTS: Through week 96, 35% of the patients in the IL-2 arm and 59% in the control arm reached the primary end point (P = .008). Median changes from baseline in the IL-2 and control arms were +51 and -64 cells/microL, respectively, for CD4 cell count (P < .001) and were +0.02 and +0.04 log(10) copies/mL, respectively, for plasma viral load (P = .93). Among patients with a baseline viral load <4.5 log(10) copies/mL, 64% in the IL-2 arm and 10% in the control arm did not reach the primary end point through week 150 (P < .001), and the time to ART initiation was deferred by 92 weeks in the IL-2 arm. The incidences of an AIDS-defining event, death, and grade 3 or 4 adverse events were similar between study arms. CONCLUSION: IL-2 increased CD4 cell counts without affecting HIV replication and allowed the initiation of ART to be deferred. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00120185 .