Impact de la résistance virale acquise dans le passé sur les stratégies antirétrovirales actuelles

In the field of HIV management, today in France, three situations continue to concern clinicians: 1) persistent low-level viremia, despite prolonged antiretroviral treatment and good self-reported compliance, 2) persistence or clearance in viral reservoir of resistance mutations selected in the past, and 3) optimal drug-reduced antiretroviral treatment in virally suppressed patients. In a first work, we showed that 72% of patients with persistent low-level viremia, with good self-reported compliance, had adequate plasma antiretroviral concentrations, and no past viral resistance explaining the persistent replication. Two years after inclusion, 72% of patients maintained low-level replication without virologic failure. In a second work, we showed the persistence of the M184V mutation, acquired in the past, in 67% of patients with suppressed viremia >5 years (detection threshold: 1%), as well as the progressive clearance of the mutation in the HIV-DNA reservoir. The two factors associated with the persistence of M184V were the duration and the level of replication under 3TC/FTC in the past. In a third work, we showed the virological efficacy of dual therapies given 5 or 4 days a week (virological success: 91% at W96), in a population highly exposed to antiretroviral treatment. Overall, these findings support the optimization of strategies, in order to reduce the exposure to antiretrovirals, including in patients with a long virological and therapeutic history.Dans le champ de la prise en charge du VIH, aujourd’hui en France, trois situations continuent d’occuper la réflexion : 1) les virémies de bas niveau persistantes, malgré un traitement ARV prolongé et une observance rapportée optimale, 2) la persistance ou la clairance dans le réservoir viral de mutations de résistance sélectionnées dans l’histoire virologique, et 3) l’allègement thérapeutique optimal chez les patients virologiquement contrôlés. Dans un premier travail, nous avons montré que 72% des patients présentant une virémie de bas niveau persistante, déclarant une bonne observance, avaient des concentrations en antirétroviraux optimales dans le sang, et étaient porteurs de virus non résistants au traitement. Deux ans après l’inclusion, 72% gardaient une virémie de bas niveau, sans échec virologique. Dans un deuxième travail, nous avons montré la persistance de la mutation M184V, archivée dans le passé, chez 67% des patients virologiquement contrôlés depuis au moins 5 ans (avec un seuil de détection à 1%), ainsi que la clairance progressive de cette mutation dans le réservoir ADN-VIH. Les deux facteurs associés à la persistance de la M184V étaient la durée et le niveau de réplication sous 3TC/FTC dans le passé. Dans un troisième travail, nous avons montré l’efficacité virologique de bithérapies administrées 5 ou 4 jours par semaines (91% de succès virologique à S96), dans une population longuement exposée aux antirétroviraux. Globalement, ces résultats s’inscrivent dans une volonté d’optimiser les stratégies en réduisant l’exposition aux antirétroviraux, y compris chez les patients ayant une longue histoire virologique et thérapeutique

Kaposi’s Sarcoma in Virally Suppressed People Living with HIV: An Emerging Condition

Since the advent of highly effective combined antiretroviral treatment (cART), and with the implementation of large HIV testing programs and universal access to cART, the burden of AIDS-related comorbidities has dramatically decreased over time. The incidence of Kaposi’s sarcoma (SK), strongly associated with HIV replication and CD4 immunosuppression, was greatly reduced. However, KS remains the most common cancer in patients living with HIV (PLHIV). HIV physicians are increasingly faced with KS in virally suppressed HIV-patients, as reflected by increasing description of case series. Though SK seem less aggressive than those in PLHIV with uncontrolled HIV-disease, some may require systemic chemotherapy. Persistent lack of specific anti-HHV-8 cellular immunity could be involved in the physiopathology of these KS. These clinical forms are a real therapeutic challenge without possible short-term improvement of anti-HHV-8 immunity, and no active replication of HIV to control. The cumulative toxicity of chemotherapies repeatedly leads to a therapeutic dead end. The introduction or maintenance of protease inhibitors in cART does not seem to have an impact on the evolution of these KS. Research programs in this emerging condition are important to consider new strategies

Impact of past viral resistance on current antiretroviral strategies

Dans le champ de la prise en charge du VIH, aujourd’hui en France, trois situations continuent d’occuper la réflexion : 1) les virémies de bas niveau persistantes, malgré un traitement ARV prolongé et une observance rapportée optimale, 2) la persistance ou la clairance dans le réservoir viral de mutations de résistance sélectionnées dans l’histoire virologique, et 3) l’allègement thérapeutique optimal chez les patients virologiquement contrôlés. Dans un premier travail, nous avons montré que 72% des patients présentant une virémie de bas niveau persistante, déclarant une bonne observance, avaient des concentrations en antirétroviraux optimales dans le sang, et étaient porteurs de virus non résistants au traitement. Deux ans après l’inclusion, 72% gardaient une virémie de bas niveau, sans échec virologique. Dans un deuxième travail, nous avons montré la persistance de la mutation M184V, archivée dans le passé, chez 67% des patients virologiquement contrôlés depuis au moins 5 ans (avec un seuil de détection à 1%), ainsi que la clairance progressive de cette mutation dans le réservoir ADN-VIH. Les deux facteurs associés à la persistance de la M184V étaient la durée et le niveau de réplication sous 3TC/FTC dans le passé. Dans un troisième travail, nous avons montré l’efficacité virologique de bithérapies administrées 5 ou 4 jours par semaines (91% de succès virologique à S96), dans une population longuement exposée aux antirétroviraux. Globalement, ces résultats s’inscrivent dans une volonté d’optimiser les stratégies en réduisant l’exposition aux antirétroviraux, y compris chez les patients ayant une longue histoire virologique et thérapeutique.In the field of HIV management, today in France, three situations continue to concern clinicians: 1) persistent low-level viremia, despite prolonged antiretroviral treatment and good self-reported compliance, 2) persistence or clearance in viral reservoir of resistance mutations selected in the past, and 3) optimal drug-reduced antiretroviral treatment in virally suppressed patients. In a first work, we showed that 72% of patients with persistent low-level viremia, with good self-reported compliance, had adequate plasma antiretroviral concentrations, and no past viral resistance explaining the persistent replication. Two years after inclusion, 72% of patients maintained low-level replication without virologic failure. In a second work, we showed the persistence of the M184V mutation, acquired in the past, in 67% of patients with suppressed viremia >5 years (detection threshold: 1%), as well as the progressive clearance of the mutation in the HIV-DNA reservoir. The two factors associated with the persistence of M184V were the duration and the level of replication under 3TC/FTC in the past. In a third work, we showed the virological efficacy of dual therapies given 5 or 4 days a week (virological success: 91% at W96), in a population highly exposed to antiretroviral treatment. Overall, these findings support the optimization of strategies, in order to reduce the exposure to antiretrovirals, including in patients with a long virological and therapeutic history

The Role of Radiotherapy in Treating Kaposi's Sarcoma in HIV Infected Patients

Kaposi's sarcoma (KS) is a radiosensitive cancer regardless of its form (classical, endemic, AIDS-related, and immunosuppressant therapy-related). Radiotherapy (RT) is an integral part of the therapeutic management of KS. RT may be used as the main treatment, in the case of solitary lesions, or as palliative therapy in the disseminated forms. The dose of RT to be delivered is 20\textendash 30 Gy by low-energy photons or by electrons. The complete response rate after RT is high, around 80\textendash 90%. This treatment is well tolerated. However, patients should be informed of the possible risk of the development of late skin sequelae and the possibility of recurrence. With the advent of highly active antiretroviral therapy (HAART), the indications for RT treatment in HIV-positive patients have decreased

Synthesizing guidance to address adherence to antiretroviral therapy and its barriers in people living with HIV: a scoping review of HIV treatment guidelines

Adherence to antiretroviral therapy (ART) is critical to suppress HIV replication and prevent its transmission to others. However, the definition of adherence, thresholds for optimal viral suppression, and how adherence challenges should be best addressed is unclear. Therefore, this study aims to synthesize the similarities and diverse approaches to adherence to defining ART adherence and interventions to address barriers within HIV care. A scoping review will be conducted on adult HIV clinical guidelines and guideline updates from developed countries following guidance from the Joanna Briggs Institute, which includes the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Databases will include Medline, Embase, and CINAHL. A search of the grey literature will be conducted through Canadian Medical Association Infobase, National Institute for Health and Care Excellence, Guideline Central, Turning Research Into Practice (TRIP), and Emergency Care Research Institute (ECRI) Guidelines Trust. For data collection, one reviewer will screen all records and full-texts, while a second reviewer will assess 20% of the texts for inter-rater reliability. Data regarding definitions of adherence, adherence thresholds, barriers to adherence, and interventions for adherence will be charted in tables. A synthesis of data will be performed using content analysis on NVivo software

Initial failure of pristinamycin treatment in a case of multidrug-resistant Mycoplasma genitalium urethritis eventually treated by sequential therapy

International audienceWe present a case of persistent Mycoplasma genitalium (MG) urethritis with documented macrolide and fluoroquinolone resistance, and we describe the A2062T mutation in the 23S rRNA gene, possibly associated with pristinamycin resistance. After several treatment failures and loss of the A2062T mutation, MG urethritis was finally cured by a sequential antibiotic treatment including minocycline

The Role of Radiotherapy in Treating Kaposi’s Sarcoma in HIV Infected Patients

Kaposi’s sarcoma (KS) is a radiosensitive cancer regardless of its form (classical, endemic, AIDS-related, and immunosuppressant therapy-related). Radiotherapy (RT) is an integral part of the therapeutic management of KS. RT may be used as the main treatment, in the case of solitary lesions, or as palliative therapy in the disseminated forms. The dose of RT to be delivered is 20–30 Gy by low-energy photons or by electrons. The complete response rate after RT is high, around 80–90%. This treatment is well tolerated. However, patients should be informed of the possible risk of the development of late skin sequelae and the possibility of recurrence. With the advent of highly active antiretroviral therapy (HAART), the indications for RT treatment in HIV-positive patients have decreased

Current and Future Tools for Diagnosis of Kaposi’s Sarcoma

International audienceKaposi’s sarcoma (KS) is a rare, atypical malignancy associated with immunosuppression and can be qualified as an opportunistic tumor, which responds to immune modulation or restoration. Four different epidemiological forms have been individualized (AIDS-related, iatrogenic, endemic or classic KS). Although clinical examination is sufficient to diagnose cutaneous lesions of KS, additional explorations are necessary in order to detect lesions involving other organs. New histological markers have been developed in recent years concerning the detection of HHV-8 latent or lytic proteins in the lesions, helping to confirm the diagnosis when it is clinically doubtful. More recently, the evaluation of the local immune response has also been shown to provide some guidance in choosing the appropriate therapeutic option when necessary. We also review the indication and the results of conventional radiological imaging and of non-invasive imaging tools such as 18F-fluoro-deoxy-glucose positron emission tomography, thermography and laser Doppler imaging for the diagnosis of KS and for the follow-up of therapeutic response in patients requiring systemic treatment

Experiences of HIV postexposure prophylaxis (PEP) among highly exposed men who have sex with men (MSM)

International audienc