Decrease in CD4 T-Cell Count and Risk of Severe Morbid Conditions in People With Human Immunodeficiency Virus Infection With Controlled Viral Load After Initiating Combination Antiretroviral Therapy Between 2006 and 2018.

BACKGROUND: A previous study showed an association between CD4 T-cell count decline in people with human immunodeficiency virus infection (PWH) with viral suppression and an increased risk of severe morbid conditions. We aimed to assess the risk of CD4 T-cell count decline (hereafter, CD4 decline), determine associated factors, and evaluate the association of this decline with the risk of severe morbid conditions (cardiovascular disease and cancer) or death. METHODS: From the Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4 French Hospital Database on HIV cohort, we selected PWH >18 years old who had been followed up for ≥2 years after viral suppression following the initiation of combination antiretroviral therapy (cART) between 2006 and 2018. CD4 decline was defined as 2 consecutive relative differences ≥15%. Among participants with such decline, we modeled CD4, CD8, and total lymphocyte counts before and after CD4 decline, using spline regression. The remaining objectives were assessed using Poisson regression, with the association between CD4 decline and the risk of severe morbid conditions or death evaluated during or after 6 months of decline. RESULTS: Among 15 714 participants (75 417 person-years), 181 presented with CD4 decline (incidence rate, 2.4/1000 person-years (95% confidence interval, 2.1-2.8). CD8 and total lymphocyte counts also showed a similar decline. Older current age and lower viral load at treatment initiation were associated with the risk of CD4 decline. The risk of severe morbid conditions or death was 11-fold higher during the first 6 months for participants who presented with CD4 decline versus those who did not (incidence rate ratio, 10.8 [95% confidence interval, 5.1-22.8]), with no significant difference after 6 months. CONCLUSIONS: In PWH with viral suppression, CD4 decline was rare and related to global lymphopenia. It was associated with a higher risk of severe morbid conditions or death during the first 6 months.

Brand-Specific Enhanced Safety Surveillance Study of GSK's Quadrivalent Seasonal Influenza Vaccine, Conducted During the COVID-19 Pandemic, in Belgium, Germany and Spain, for the 2020/21 Season.

INTRODUCTION: Seasonal influenza poses a major public health burden worldwide. Influenza vaccines, updated yearly to match circulating strains based on World Health Organization (WHO) recommendations, are the cornerstone of prevention and require regular monitoring. The COVID-19 pandemic is expected to cause logistical, site access and medical staff constraints and could affect the safety profile of influenza vaccines. METHODS: Following European Medicines Agency guidance, an enhanced safety surveillance (ESS) study assessed the frequency and severity of predefined and other adverse events (AEs) occurring within 7 days of receiving GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4), in Belgium, Germany and Spain in 2020/21, using adverse drug reaction (ADR) cards. RESULTS: During the 2020/21 influenza season, 1054 participants vaccinated with GSK's IIV4 were enrolled (all adults in Belgium and Germany, 30% adults/70% children in Spain); 96 eligible children received a second dose. Overall, 1042 participants completed the study. After doses 1 and 2, 98.9% and 100% of participants, respectively, returned their completed ADR card. After doses 1 and 2, 37.8% (398/1054) and 13.5% (13/96) of participants, respectively, reported at least one AE. The most frequently reported categories of AEs were "general disorders and administration site conditions" (e.g. injection site pain) and "nervous system disorders" (e.g. headache). There were no deaths or serious AEs deemed related to GSK's IIV4. CONCLUSION: This ESS study assessed AEs in near real time. The COVID-19 pandemic did not alter the safety profile of GSK's IIV4. No safety signals were detected during the study, which confirms the excellent safety profile of GSK's IIV4.

CD4+ cell count recovery after combined antiretroviral therapy in the modern combined antiretroviral therapy era.

OBJECTIVE: To assess CD4 recovery after combined antiretroviral therapy (cART) initiation with sustained virologic control. DESIGN: Cohort study based on the French Hospital Database on HIV (FHDH-ANRS CO4). METHODS: We selected naive HIV-1-infected individuals initiating cART between 2006 and 2014 with CD4 cell counts less than 500 cells/µl who achieved virologic control, defined as two consecutive viral loads less than 50 copies/ml. We estimated the cumulative incidence of CD4 recovery at least 500 cells/µl and identified associated factors, considering 'virologic failure,' 'loss to follow-up' and 'death' as competing events. RESULTS: We analyzed 6050 individuals with a median follow-up of 14.2 months since virologic control. The cumulative incidence for CD4 recovery after 6 years of virologic control reached 69.7%. The main factor associated with CD4 recovery was the CD4 count at treatment initiation [subdistribution hazard ratio (sHR) 9.64, 95% confidence interval (95% CI) 8.12-11.43 for CD4 cell counts between 350 and 500 cells/µl compared with CD4 cell counts <100 cells/µl). A higher CD4/CD8 ratio at initiation was also independently associated with a higher probability of CD4 recovery [sHR 1.67; 95% CI 1.34-2.09] for a CD4/CD8 ratio ≥1.00 vs. < 0.30). Higher viral load at initiation was also associated with a higher probability of CD4 recovery, whereas time to viral suppression was not. CONCLUSION: After 6 years of sustained virologic control, a large majority of the population achieved CD4 recovery. A higher CD4 cell count at initiation was a strong predictor of CD4 recovery and, to a lesser extent, a higher CD4/CD8 ratio at initiation. These results confirm the necessity of early treatment.