Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life.

BACKGROUND: Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients' quality of life. METHODS: In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. RESULTS: Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54-4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32-4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97-35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches. CONCLUSION: Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration. CLINICAL TRIAL: NCT01730690.

Prophylaxis by doravirine-lamivudine-tenofovir disoproxil fumarate or elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide after sexual exposure to HIV.

HIV post- exposure prophylaxis (PEP) is a prevention tool for individuals with a recent potential exposure to HIV. Doravirine has been available since 2019 in combination with tenofovir disoproxil fumarate and lamivudine and has not been evaluated as a PEP. DOR/3TC/TDF is our department's most commonly prescribed PEP treatment since 2021. This study evaluates the completion rate of the DOR/3TC/TDF as compared to EVG/c/FTC/TAF for PEP, which was the regimen prescribed until 2020 in our hospital.This retrospective observational study was conducted between January 2020 and September 2021. The subjects included consecutively were adults who consulted for an HIV sexual exposure accident and for whom DOR/3TC/TDF in 2021 or EVG/c/FTC/TAF in 2020 was prescribed. The outcomes were the completion rate to the end of treatment (28 days), the seroconversion rate, and the description of side effects.During the study period, 311 people were included: 140 treated with DOR/3TC/TDF and 171 treated with EVGc/FTC/TAF. Considering subjects with a follow-up visit, the completion rate was 96.8% (90/93) in the DOR/3TC/TDF group, and 94.6% (123/130) in the EVG/c/FTC/TAF group (p-value: 0.53). The number of people lost to follow-up was nearly equivalent in both groups: 27.1% (38/140) in the DOR/3TC/TDF group and 23.4% (40/171) in the EVG/c/FTC/TAF group (p-value: 0.45). A side effect was described for 38% (36/94) in the DOR/3TC/TDF group, and 29.7% (38/128) in the EVG/c/FTC/TAF group. No cases of seroconversion were observed.DOR/3TC/TDF appears to have a similar safety profile to EVG/c/FTC/TAF. Due to its lower cost, it seems to be a treatment option for consideration in the context of HIV-exposure accidents.

Prospective evaluation of blood Epstein-Barr virus DNA load and antibody profile in HIV-related non-Hodgkin lymphomas.

OBJECTIVES: The value of Epstein-Barr virus (EBV) biomarkers on the prognosis of HIV-related non-Hodgkin's lymphoma (NHL) has been poorly explored in the combined antiretroviral therapy (cART) era. DESIGN: We evaluated EBV DNA load and EBV antibodies in HIV-NHL patients enrolled in the French ANRS-CO16 Lymphovir Cohort between 2008 and 2015. METHODS: Whole blood and plasma EBV DNA load and serological profiles were analyzed in 76 HIV-infected patients at diagnosis of NHL and 6 months after the initiation of chemotherapy. RESULTS: Prechemotherapy whole blood (WB) and plasma EBV DNA loads were positive for 80 and 45% of HIV-NHL patients, respectively. Pretreatment WB EBV DNA positivity was associated with a positive plasma HIV-1 RNA load (relative risk (RR), 4.42 [1.33; 14.72]) and plasma EBV DNA positivity with EBV in situ detection (RR 10.62 [2.38; 47.49]). Following chemotherapy, the proportions of patients with positive WB or plasma EBV DNA declined from 81 to 23% (P < 0.0001) and from 43 to 8% (P < 0.0001), respectively. Estimated 2-year progression-free survival did not differ according to prechemotherapy WB positivity (82% versus 67%, P = 0.15) or plasma EBV DNA positivity (76% versus 81%, P  = 0.52). CONCLUSIONS: The plasma EBV DNA load correlates with in situ EBV detection. The WB EBV DNA load correlates with HIV load. WB and plasma EBV DNA loads at NHL diagnosis do not constitute prognostic markers for HIV-NHL patients in the modern cART era.

Hepatitis C virus or hepatitis B virus coinfection and lymphoma risk in people living with HIV.

OBJECTIVE: Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era. DESIGN: We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort. METHODS: Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4). RESULTS: Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome. CONCLUSION: In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.

Epstein-Barr virus biomarkers have no prognostic value in HIV-related Hodgkin lymphoma in the modern combined antiretroviral therapy era.

OBJECTIVES: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis of HIV-related classical Hodgkin lymphoma (HIV-cHL). The utility of EBV molecular and serological biomarkers has scarcely been examined in HIV-cHL in the recent combined antiretroviral therapy (cART) era. DESIGN: We evaluated EBV DNA load and a panel of EBV antibodies in HIV-cHL patients prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. METHODS: Pretreatment whole blood, plasma EBV DNA load and serological profiles were analysed in 63 HIV-infected patients diagnosed with cHL. For the 42 patients with available material, comparisons were performed between values at diagnosis and 6 months after the initiation of chemotherapy. RESULTS: Pretreatment whole blood and plasma EBV DNA loads were positive in 84 and 59% of HIV-cHL patients, respectively. Two-year progression-free survival estimates did not differ between the patients with pretreatment whole blood (n = 53) or plasma (n = 37) EBV DNA(+) and the patients with pretreatment whole blood (n = 10) or plasma (n = 26) EBV DNA(-) (92 vs. 80% or 89 vs. 92%, P = 0.36 and 0.47, respectively). At diagnosis, 47% of patients harboured an EBV reactivation serological profile. Following chemotherapy, whole blood and plasma EBV DNA levels significantly declined from medians of 1570 [interquartile range, 230-3760) and 73 (0-320) copies/ml to 690 (0-1830) and 0 (0-0) copies/ml, respectively (P = 0.02 and P < 0.0001, respectively]. Anti-EBV IgG antibody level significantly dropped at 6-month follow-up (P = 0.004). CONCLUSION: Whole blood and plasma EBV DNA loads do not constitute prognostic markers in HIV-cHL patients in the modern cART era.

Outcomes for HIV-associated diffuse large B-cell lymphoma in the modern combined antiretroviral therapy era.

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) remains among the most frequent malignancies in persons living with HIV (PLWHIV). Survival among patients with HIV-associated diffuse large B-cell lymphoma (DLBCL), the most frequent NHL subtype, has improved markedly in recent years. We aimed to analyze characteristics and outcomes of DLBCL in HIV-infected patients in the era of modern combined antiretroviral therapy (cART). DESIGN: PLWHIV with lymphoma were prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. We compared the patients treated with R-CHOP) (rituximab, cyclophosphamide, daunorubicin, vin-cristine, prednisolone) with HIV-negative DLBCL patients enrolled simultaneously in the R-CHOP arms of Lymphoma Study Association trials. RESULTS: Among 110 PLWHIV with NHL, 52 (47%) had systemic DLBCL. These 52 cases had frequent extranodal disease (81%), poor performance status (35%) and advanced age-adjusted international prognostic index (aaIPI) (58%), and were mainly treated with R-CHOP (n = 44, 85%). Their median CD4 T-cell count was 233 cells/µl, and 79% of patients were on cART. The 2-year overall and progression-free survival rates were both 75% (95% confidence interval: 64%, 88%). Factors associated with progression or death in univariate analysis were poor performance status [hazard ratio: 3.3 (1.2, 8.9)], more than one extranodal site [hazard ratio: 3.4 (1.1, 10.5)] and an advanced aaIPI [hazard ratio: 3.7 (1.0, 13.1)]. Progression-free survival after R-CHOP therapy did not differ from that of the HIV-negative counterparts (P = 0.11). CONCLUSION: In the recent cART era, despite frequent high-risk features, the 2-year overall survival of HIV-DLBCL patients reaches 75%. Outcomes after R-CHOP therapy are similar to those of HIV-negative patients with similar aaIPI.

First Report of CD4 Lymphopenia and Defective Neutrophil Functions in a Patient with Amebiasis Associated with CMV Reactivation and Severe Bacterial and Fungal Infections.

We report the case of a patient with acute necrotizing colitis due to invasive amebiasis associated with CD4 lymphopenia and impaired neutrophil responses. The course of the disease was characterized by CMV reactivation and severe and recurrent bacterial and fungal infections, which might be related to the decreased CD4 T cell count and the impaired functional capacities of neutrophils, respectively. The clinical outcome was positive with normalization of both CD4 cell count and neutrophil functions.

Evaluation of tolerability with the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate for post-HIV exposure prophylaxis.

BACKGROUND: The preferred regimen for HIV post-exposure prophylaxis (PEP) is based mainly on safety and tolerability because it is given to immunocompetent people without HIV infection for a limited time (28 days). The frequency of adverse events (AEs) may be > 60%. Although AEs are generally not severe, they can lead to lack of adherence and failure to complete the regimen. We evaluated the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild®) prescribed as one pill taken once daily for HIV PEP in terms of tolerability and adherence. METHODS: This was a prospective cohort study conducted in one hospital in Paris (April to December 2015. Each participant receiving the PEP treatment (FTC-150 mg/TDF-245 mg/elvitegravir-200 mg/cobicistat 150 mg once daily) at the pharmacy of the hospital were recruited consecutively. A clinical visit was planned at 8 weeks after sexual exposure. Reminders were sent to participants who missed the appointment. A standardized questionnaire was administered to evaluate completeness and tolerability at week 8. RESULTS: Overall, 284 participants (86% men; 80% MSM; median age 30 years) were prescribed Stribild®; 50 stopped after reassessment of risk. Among 234 participants who effectively received PEP, 215 (92%) completed 28 days of PEP with only three who switched from Stribild® to another PEP because of side effects. More than 60% of participants reported at least one AE, which were mild to moderate. Fatigue, central neurological and abdominal side effects were the most frequently reported. CONCLUSIONS: Stribild® seems to be a good option for HIV PEP due to the easiness of use, the side effects profile and the high completion rate.

High Risk Features Contrast With Favorable Outcomes in HIV-associated Hodgkin Lymphoma in the Modern cART Era, ANRS CO16 LYMPHOVIR Cohort.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era. METHODS: We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL. RESULTS: Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients. CONCLUSIONS: Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients.

Determinants of adherence to non-occupational post HIV exposure prophylaxis.

We conducted a study on 140 patients who sought advice at hospital after a non-occupational exposure. The full 28-day course of prophylactic antiretroviral therapy was completed by 109 patients. No HIV contamination was observed. Factors associated with suboptimal adherence were African ethnicity [odds ratio (OR) 13.3, 2.02-87.54] and oral sexual intercourse (OR 8.35, 1.66-41.99). Compliance with prophylactic antiretroviral therapy can be increased by addressing social and psychological barriers to adherence.