Humoral response to SARS-CoV-2 vaccines in people living with HIV.

PURPOSE: To describe the humoral immune response to COVID-19 vaccines in people living with HIV and identify factors associated with the magnitude of anti-SARS-CoV-2 antibody concentrations. METHODS: Retrospective analysis of electronic patient files in a big single HIV center in Munich, Germany. Non-parametric methods were used for descriptive and comparative statistics. Generalized linear models were used to analyze associations of general and HIV-specific variables with anti-SARS-CoV-2 antibody concentrations after standard vaccination. RESULT: Overall, 665 people living with HIV were included into the analysis (median age: 53 [IQR: 43; 59]), 560 [84.2%] males). Median concentration of anti-SARS-CoV-2-antibodies was 1400 (IQR 664; 2130) BAU/mL. In 18 (2.7%) subjects, antibody concentrations below the threshold of 34 BAU/mL were found. Among PLWH with CD4 cell count < 200 cells/µL, median anti-SARS-CoV-2-Abs were 197 (IQR 44.6; 537.2) as compared to 1420 (IQR 687; 2216) for the group ≥ 200 cells/µL (p < 0.001). In a cumulative logit model, a vaccination scheme including an mRNA vaccine [OR: 4.64 (3.58; 6.02)], being female [OR: 2.14 (1.76; 2.61)], and having higher CD4 cells [OR per 100 cells/µL: 1.06 (1.04; 1.08)] were significantly associated with anti-SARS-CoV-2 antibody concentrations in higher quartiles, when adjusted for the time after vaccination. CONCLUSION: We found a robust antibody response in people living with HIV undergoing standard vaccination against SARS-CoV-2. mRNA-containing vaccination schemes, being female, and having a higher CD4 cell count was associated with a higher concentration of antibodies in people living with HIV in our study sample. Particularly in the subgroup with CD4 cell counts < 200 cells/µL, antibody response was poor.

Immune deficiency is a risk factor for severe COVID-19 in people living with HIV.

OBJECTIVES: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID-19 pandemic. Clinical data on patients co-infected with HIV and SARS-CoV-2 are still scarce. METHODS: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings. COVID-19 was clinically classified as to be mild-to-moderate or severe. RESULTS: Of 175 patients, 49 (28%) had severe COVID-19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID-19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID-19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS-defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID-19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26-6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. CONCLUSIONS: In PLWH, immune deficiency is a possible risk factor for severe COVID-19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.

COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients.

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.

Tenofovir Disoproxil Fumarate Is Associated with a Set-Point Variation in the Calcium-Parathyroid Hormone-Vitamin D Axis: Results from a German Cohort.

BACKGROUND: Higher levels of parathyroid hormone have been associated with the use of tenofovir disoproxil fumarate (TDF) in people with and without HIV infection. Yet, alterations in calcium levels have never been elucidated in detail. OBJECTIVE: To compare the association of parathyroid hormone with serum calcium levels and other markers of calcium and bone metabolism in people living with HIV on TDF- and non-TDF-containing antiretroviral therapy. PATIENTS AND METHODS: A retrospective single center cohort study in Munich, Germany. Median and interquartile ranges and absolute and relative frequencies were used to describe continuous and categorical variables, respectively. The Mann-Whitney U test and chi2-test were used for comparisons. Multivariate median regression was performed in a stepwise backward approach. RESULTS: 1,002 patients were included (786 (78.4%) male; median age 48 (40-55) years). 564 patients (56.3%) had a TDF-containing ART regimen. PTH concentrations were 46.9 (33.0-64.7) pg/mL and 35.2 (26.4-55.4) pg/mL (P=0.001), 43.3 (30.8-59.8) pg/mL and 31.8 (22.3-49.6) pg/mL (P < 0.001), 46.1 (29.5-65.4) pg/mL and 33.4 (22.6-50.1) pg/mL (P < 0.001), and 37.8 (25.3-57.9) pg/mL and 33.8 (20.1-45.3) pg/mL (P=0.012) within the first, second, third, and fourth quartile of corrected calcium levels for patients with and without TDF-containing ART, respectively. In multivariate median regression, PTH concentration was significantly associated with Cacorr. (-32.2 (-49.8 to -14.8); P < 0.001), female sex (5.2 (1.2-9.2); P=0.010), 25(OH)D (-0.4 (-0.5 to -0.3); P < 0.001), and TDF-use (9.2 (6.0-12.5); P < 0.001). DISCUSSION: Higher levels of PTH seem to be needed to maintain normal calcium levels in PLWH on TDF-containing ART compared to non-TDF-containing ART. Optimal concentrations for 25-hydroxy vitamin D and calcium might therefore be different in people using TDF than expected from general populations but also people living with HIV with non-TDF-containing antiretroviral therapy. This might require different supplementation strategies but warrants further investigation.

Surfactant protein D regulates chemotaxis and degranulation of human eosinophils.

The collectin surfactant protein D (SP-D) is an important component of the pulmonary innate host defence. Up to now, little is known about the regulation of eosinophil function by SP-D. Various murine models of pulmonary hypersensitivity suggest that SP-D may be a potent anti-allergic protein. We investigated the modulation of eosinophil chemotaxis and degranulation by human SP-D. SP-D markedly inhibited the chemotaxis of eosinophils triggered by eotaxin, a major tissue-derived CC-chemokine, as shown in a modified Boyden chamber assay. In addition, degranulation of ECP in response to Ca2+ ionophore, immobilized IgG and serum from allergic patients was inhibited by SP-D. In a fixed-cell enzyme linked immunosorbent assay and in flow cytometry, SP-D bound to eosinophils. This binding was saturable and was inhibited by the addition of maltose and ethylenediaminetetraacetic acid, suggesting the involvement of the carbohydrate recognition domain of SP-D. In addition, flow cytometry showed significant interaction of SP-D with CD32 (FcgammaII receptor) on eosinophils, which might explain the inhibitory effect of SP-D on the IgG and serum-triggered eosinophil cationic protein degranulation of eosinophils. Our data further support the concept of an anti-inflammatory function of SP-D in the lung of patients with allergic diseases.