Epidemiological impact of Neisseria gonorrhoeae and Chlamydia trachomatis screening in men having sex with men: a modelling study.

OBJECTIVES: The impact of the systematic screening of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in men having sex with men (MSM) on these pathogens' epidemiology remains unclear. We conducted a modelling study to analyse this impact in French MSM. METHODS: We modelled NG and CT transmission using a site-specific deterministic compartmental model. We calibrated NG and CT prevalence at baseline using results from MSM enrolled in the Dat'AIDS cohort. The baseline scenario was based on 1 million MSM, 40 000 of whom were tested every 90 days and 960 000 every 200 days. Incidence rate ratios (IRRs) at steady state were simulated for NG, CT, NG and/or CT infections, for different combinations of tested sites, testing frequency and numbers of frequently tested patients. RESULTS: The observed prevalence rate was 11.0%, 10.5% and 19.1% for NG, CT and NG and/or CT infections. The baseline incidence rate was estimated at 138.2 per year per 100 individuals (/100PY), 86.8/100PY and 225.0/100PY for NG, CT and NG and/or CT infections. Systematically testing anal, pharyngeal and urethral sites at the same time reduced incidence by 14%, 23% and 18% (IRR: 0.86, 0.77 and 0.82) for NG, CT and NG and/or CT infections. Reducing the screening interval to 60 days in frequently tested patients reduced incidence by 20%, 29% and 24% (IRR: 0.80, 0.71 and 0.76) for NG, CT and NG and/or CT infections. Increasing the number of frequently tested patients to 200 000 reduced incidence by 29%, 40% and 33% (IRR: 0.71, 0.60 and 0.67) for NG, CT and NG and/or CT infections. No realistic scenario could decrease pathogens' incidence by more than 50%. CONCLUSIONS: To curb the epidemic of NG and CT in MSM, it would not only be necessary to drastically increase screening, but also to add other combined interventions.

Epidemiology and characteristics of Paget's disease of bone in a French nationwide HIV cohort.

Paget's disease of bone (PDB) has rarely been reported in people with HIV (PWH). We describe the prevalence and characteristics of patients with PDB in the French multicenter Dat'AIDS cohort. Among 49 698 PWH actively followed in 2022, 9 had a diagnosis of PDB. The overall prevalence of PDB was 0.02% [95% confidence interval (CI) 0.01-0.03]. The prevalence of PDB in PWH is very low and does not appear to differ from the non-HIV population.

Acquisition du virus de l'immunodéficience humaine et parcours de vie d'hommes ayant des rapports sexuels avec d'autres hommes et ayant émigré en France : une enquête exploratoire.

INTRODUCTION: The ANRS 14058 Ganymede study aims to determine the proportion post-migration HIV-seroconversion in a sample of HIV-positive men having sex with men (MSM) born outside of France and receiving medical care in Paris region (Île-de-France). The study, based on a self-questionnaire, is also focused on the life course of these MSM before, during and after the migration process. PURPOSE OF RESEARCH: The paper refers to a qualitative exploratory study, taking place as a prerequisite for the Ganymede study, in order to refine its questionnaire. The purpose of these interviews was also to explore the migratory motivations and experiences, the sexual biography, and the health history, of a sample of seropositive MSM born outside of France, and to illustrate the diversity of this epidemiological category. RESULTS: Forteen respondents participated in the interview study. Nine of them have learned of their HIV-positive status after having emigrated to France. None of the respondents mentioned a major barrier to medical care access and HIV follow-up. The obstacles they reported were related to the coverage of medical expenses, due to their possible precarious legal and social situation. These men were exposed to the effects of power relations, leading to discrimination and violence, whose wider impacts on health were weakly evoked. CONCLUSIONS: Although the findings of the exploratory study are not to be generalized, they illustrate the health issues of the interviewees, and the wide diversity of their biographies and life courses, emphasizing the impact of gender and class power relations as a source of social and health inequalities, and precariousness. They invite therefore to describe this epidemiological category of "MSM born outside of France" in a more heterogeneous way.

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.

Immune Reconstitution Inflammatory Syndrome Associated Kaposi Sarcoma.

People living with HIV (PLWH) with advanced immunosuppression who initiate antiretroviral therapy (ART) are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS). Although ART is responsible for AIDS- associated Kaposi sarcoma (KS) improvement and resolution, new onset (unmasking KS-IRIS) or sudden progression of preexisting KS (paradoxical KS-IRIS) can occur after a time delay of between a few days and 6 months after the initiation or resumption of ART, even in patients with a low degree of immunocompromise. KS-IRIS incidence varies from 2.4% to 39%, depending on study design, populations, and geographic regions. Risk factors for developing KS-IRIS include advanced KS tumor stage (T1), pre-treatment HIV viral load >5 log10 copies/mL, detectable pre-treatment plasma-KSHV, and initiation of ART alone without concurrent chemotherapy. Both paradoxical and unmasking KS-IRIS have been associated with significant morbidity and mortality, and thrombocytopenia (<100,000 platelets/mm3 at 12 weeks) has been associated with death. KS-IRIS is not to be considered as ART failure, and an ART regimen must be pursued. Systemic chemotherapy for KS in conjunction with ART is recommended and, in contrast with management of IRIS for other opportunistic infections, glucocorticoids are contra-indicated. Despite our preliminary results, the place of targeted therapies in the prevention or treatment of KS-IRIS needs further assessment.

Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma.

In patients with Kaposi's sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.

No increased risk of Kaposi sarcoma relapse in patients with controlled HIV-1 infection after switching protease inhibitor-based antiretroviral therapy.

OBJECTIVES: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication. METHODS: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen. RESULTS: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/µL (range 225-560) for switching patients, compared with 362 and 136 cells/µL for the other two patients. CONCLUSIONS: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

Current and Future Tools for Diagnosis of Kaposi's Sarcoma.

Kaposi'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.

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.

New Kaposi's sarcoma-associated herpesvirus variant in men who have sex with men associated with severe pathologies.

BACKGROUND: Kaposi sarcoma (KS)-associated herpesvirus (KSHV) subtype depends mostly on patient origin. The current study aimed to assess KSHV diversity in a population of men who have sex with men (MSM) living in France. METHODS: The study included 264 patients. In 65 MSM, including 57 human immunodeficiency virus (HIV)-infected men with KS, multicentric Castleman disease, or primary effusion lymphoma and 8 HIV-uninfected men receiving HIV preexposure prophylaxis (PrEP), we performed KSHV typing with K1 open reading frame Sanger and KSHV whole-genome sequencing. In 199 other patients, we performed real-time polymerase chain reaction screening for the new variant. RESULTS: We found that 51% of KSHV-strains were subtype C (85% C3), and 33% were subtype A. Four patients with severe KSHV disease (2 with visceral KS, 1 with multicentric Castleman disease, and 1 with primary effusion lymphoma) and 1 asymptomatic PrEP user had a new variant resembling the Ugandan subtype F, but with different K1 open reading frame and KSHV whole-genome sequences and a different epidemiological context (MSM vs African population). Its prevalence was 4.5% in Caucasian MSM, and it was absent in other epidemiological groups. CONCLUSIONS: Subtype C predominated among MSM living in France. The new F variant was identified in Caucasian MSM and associated with severe KSHV disease, suggesting that subtype F could be split into F1 and F2 variants. Careful screening for this variant may be required in MSM, given the severe clinical presentation of associated diseases.

Recurrence and Occurrence of Kaposi's Sarcoma in Patients Living With Human Immunodeficiency Virus (HIV) and on Antiretroviral Therapy, Despite Suppressed HIV Viremia.

In 21 cutaneous and/or visceral Kaposi's sarcoma cases, occurring in patients living with human immunodeficiency virus (HIV) who were on antiretroviral therapy with suppressed HIV viremia and high CD4 T cell counts, the efficacy of conventional chemotherapies was limited due to cumulative toxicities, comedications, and a lack of immune improvement.

Plasma cystatin C as a marker for estimated glomerular filtration rate assessment in HIV-1-infected patients treated with dolutegravir-based ART.

Objectives: Inhibition of the organic cation transporter-2 renal tubule transporter by dolutegravir leads to serum creatinine increase. Serum cystatin C is a non-organic cation transporter-2-dependent marker, possibly enabling glomerular filtration rate (GFR) estimation under dolutegravir. Our goal was to evaluate the changes in creatinine- and cystatin C-based estimated GFR values before and after dolutegravir initiation. Methods: Creatinine and cystatin measurements were carried out on frozen plasma samples from HIV-1-infected patients, before and after dolutegravir initiation, between October 2016 and March 2017 at Pitié-Salpêtrière Hospital. CKD-EPI equations were used to estimate mean GFR from creatinine and cystatin C values. Variations were analysed by paired t-test. Results: Forty-four patients were included [median age = 48 years (IQR 36-58) and median CD4 count = 592 cells/mm3 (IQR 388-728)], including 6 ART-naive patients and 38 on switch strategies [72% with viral load <50 copies/mL and median ART duration = 13 years (IQR 5-20)]. Before dolutegravir initiation (median time = 41 days), 19 patients (43%) had creatinine-based estimated GFR <90 mL/min/1.73 m2 and 11 (25%) had cystatin C-based estimated GFR <90 mL/min/1.73 m2. After dolutegravir initiation, serum creatinine values significantly increased (+8.6 µmol/L, 95% CI +5.8; +11.4, P < 0.001) and associated estimated GFR significantly decreased (-7.7 mL/min/1.73 m2, 95% CI -10.4; -5.1, P < 0.001). In contrast, there was no significant change in cystatin C value variation and associated estimated GFR. The same results were observed regardless of renal function at baseline. Conclusions: Creatinine values increased after dolutegravir initiation, whereas no change was observed for cystatin C values. Use of cystatin C may enable better understanding of plasma creatinine fluctuations after dolutegravir initiation, particularly in high-risk renal patients.