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Topics in Antiviral Medicine ; 30(1 SUPPL):179, 2022.
Article in English | EMBASE | ID: covidwho-1880650


Background: The impact of some antiretrovirals against SARS-CoV-2 infection and disease severity is conflicting. We evaluated the effect of tenofovir alafenamide/emtricitabine (TAF/FTC) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with (PLWH). Methods: We conducted a propensity score-matched analysis leveraging data from the PISCIS cohort of PLWH in Catalonia (Spain). We matched for TAF/FTC versus ABC/3TC in a ratio of 1:1, and 1:3 for TDF/FTC versus ABC/3TC, and TDF/FTC versus TAF/FTC. We used logistic regression to assess the association between tenofovir-based ART and SARS-CoV-2 diagnosis and associated hospitalisation. Results: In our entire cohort [median age: 46.1 years, 82.3% males], 7550 PLWH were being treated with TAF/FTC, 1020 receiving TDF/FTC, and 4135 receiving ABC/3TC. After propensity score-matching, SARS-CoV-2 diagnosis rates were the same in TAF/FTC versus ABC/3TC recipients (12.2% vs 12.2%, P=1.00);lower among TDF/FTC versus ABC/3TC recipients (9.7% vs 12.4%, P=0.05) with borderline significance;and lower among TDF/FTC versus TAF/FTC recipients (9.7% vs 12.6%, P=0.03). In well-adjusted logistic regression models, TAF/FTC was not associated with reduced SARS-CoV-2 diagnosis (adjusted odds ratio [aOR] 0.97;95% confidence interval [CI], 0.83-1.12) or associated hospitalisation (aOR 0.95;95% CI, 0.62-1.45). TDF/FTC compared to ABC/3TC, was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.81;95% CI, 0.61-1.07) or hospitalisation (aOR 0.49;95% CI, 0.14-1.27). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.81;95% CI, 0.61-1.07) or associated hospitalisation (aOR 0.47;95% CI, 0.14-1.22) compared to TAF/FTC. Conclusion: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalisations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure or not should not modify the preventive or therapeutic SARS-CoV-2 infection management.

Topics in Antiviral Medicine ; 29(1):86-87, 2021.
Article in English | EMBASE | ID: covidwho-1250792


Background: Understanding the adaptive immune response to SARS-CoV-2, kinetics, persistence and their relationship with the disease severity would be crucial in order to predict recurrences, reinfections and could serve in the design of vaccination strategies. We sought to characterize IgG and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients who were admitted to hospital with COVID-19 disease. Methods: All patients admitted between March-April 2020 with moderate, severe and critical SARS-CoV-2 pneumonia were prospectively studied. Clinical, laboratory data and IgG against SARS-CoV-2 levels were assessed at baseline (upon admission) and months 1, 3 and 6. NAbs were assessed at month 1, 3 and 6. IgG against the SARS-CoV-2 spike (S) protein was measured in serum by chemiluminescence (LIAISON® SARS-CoV-2 S1/S2, DiaSorin) and results were expressed in arbitrary units (AU)/mL. The neutralizing activity of plasma samples was analyzed in a 293T/hACE2 cell infection test using a surrogate viral inhibition assay that uses human immunodeficiency virus type 1 (HIV-1)-based virus expressing SARS-CoV-2 S protein and Luciferase. For neutralization assays, pseudoviruses were incubated with increasing plasma dilutions (range 1/60-1/14,580) in order to obtain the ID50 values. Results: A total of 110 patients who were discharged from hospital were recruited. Median (range) age was 61 (57-71);61.2% were male and most reported comorbidities were hypertension (39.6%), diabetes (24.3%) and obesity (19.8%). Median time from symptoms onset to admission was 9 days (range 7-11). Median (range) IgG levels (AU/mL) at baseline and months 1, 3 and 6 were 48 (28-81), 168 (134-210), 140 (112-171) and 146 (104-206) respectively. No significant differences were observed in median IgG fold change values up to month 6 among severity groups. Median (range) ID50 values for NAbs at months 1, 3 and 6 were 3938 (1958-6407), 4344 (2335-6752) and 424 (124-1022) respectively. NAb titers presented a significant decrease (overall-10.2-fold change from maximal values) without differences among severity groups (Figure 1 a and b). No reinfections occurred. Conclusion: Specific humoral immune response to SARS CoV-2 in patients requiring hospital admission characterizes for a clear peak between 30 and 90 days after admission followed by a significant decline in titer of NAbs by day 180 regardless of disease severity. Longer follow-up may help to determine the longevity of the specific immune response.

Topics in Antiviral Medicine ; 29(1):248, 2021.
Article in English | EMBASE | ID: covidwho-1249965


Background: Several large cohort studies have shown that adults with HIV (PWH) may have worse COVID-19 outcomes than non-HIV-infected persons. Whether it may be due to a higher frequency of co-morbidities or to a direct HIV effect is currently unclear. Methods: We performed a nation-wide multicenter prospective case-cohort study. Consecutive COVID-19-confirmed PWH (cases) admitted in 39 Spanish centers were matched 1:1 to COVID-19-confirmed non-HIV-infected adults (controls) for center, calendar week, age and gender. The contribution for death of HIV adjusted for co-morbidities was assessed in the whole population, and the contribution of immunological, virological, and antiretroviral factors only in the PWH group. Conditional logistic, random-effects logit and Fine-Gray competing-risks regression models were estimated. Results: From 26/Feb to 21/Sep 2020, 204 cases and 204 controls were included. Median (IQR) age was 54 (47-60) years and 85% were men. Among PWH, 33% had prior AIDS events, current median CD4 cells/mm3 were 521 (IQR 310-756), 14% had CD4<200/mm3, and 90% had HIV suppressed;antiretrovirals were: 17% NNRTI, 23% PI, 70% InSTI, 89% NRTI, 6% TDF, 45% TAF, and 31% ABC. Chronic liver disease (aOR 8.68, 95%CI 1.51-49.97, P=0.0156), cardiovascular disease (aOR 2.09, 95%CI 1.19-3.68, P=0.0103), and obesity (aOR 0.30, 95%CI 0.19-0.49, P<0.0001) significantly differed between cases and controls. Twenty (9.8%) cases and 7 (3.4%) controls died. HIV infection was associated with a higher risk of death after adjustment for chronic liver disease, cardiovascular disease, and obesity (aOR 5.27, 95%CI 1.00-27.72, P=0.0499) and a higher incidence of death (subHR 3.45, 95%CI 1.47-8.11, P=0.0045). Increasing age, hypertension, diabetes, COPD, decreasing haemoglobin and leukocytes, and CKD-EPI eGFR ≤90 mL/min/1.73 m2 were associated with death in cases, while increasing age and neoplasia were associated with death in controls. Only increasing age and COPD in cases and neoplasia in controls remained associated with death in the adjusted logistic regression. Current or nadir CD4 counts and CD4/CD8 ratio, detectable HIV RNA, and specific antiretroviral agents were not associated with death. Conclusion: In this cohort of COVID-19 in-patients, risk of death was higher in PWH than in non-HIV-infected controls. Several co-morbidities through increasing age, but not immunological, virological, or antiretroviral factors, were associated with a higher risk of death in PWH.