Acute HIV-1 and SARS-CoV-2 Infections Share Slan+ Monocyte Depletion-Evidence from an Hyperacute HIV-1 Case Report.

Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/-CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.

Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients.

The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.

Severe cavitary pneumonia caused by Bordetella bronchiseptica in an HIV-infected patient / Neumonía cavitaria grave causada por Bordetella bronchiseptica en un paciente infectado con VIH

No disponible

Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation.

BACKGROUND: Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. METHODS: We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. RESULTS: We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. CONCLUSIONS: This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.

Early ART in Acute HIV-1 Infection: Impact on the B-Cell Compartment.

HIV-1 infection induces B cell defects, not fully recovered upon antiretroviral therapy (ART). Acute infection and the early start of ART provide unique settings to address the impact of HIV on the B cell compartment. We took advantage of a cohort of 21 seroconverters, grouped according to the presence of severe manifestations likely mediated by antibodies or immune complexes, such as Guillain-Barré syndrome and autoimmune thrombocytopenic purpura, with a follow-up of 8 weeks upon effective ART. We combined B and T cell phenotyping with serum immunoglobulin level measurement and quantification of sj-KRECs and ΔB to estimate bone marrow output and peripheral proliferative history of B cells, respectively. We observed marked B cell disturbances, notably a significant expansion of cells expressing low levels of CD21, in parallel with markers of both impaired bone marrow output and increased peripheral B cell proliferation. This B cell dysregulation is likely to contribute to the severe immune-mediated conditions, as attested by the higher serum IgG and the reduced levels of sj-KRECs with increased ΔB in these individuals as compared to those patients with mild disease. Nevertheless, upon starting ART, the dynamic of B cell recovery was not distinct in the two groups, featuring both persistent alterations by week 8. Overall, we showed for the first time that acute HIV-1 infection is associated with decreased bone marrow B cell output assessed by sj-KRECs. Our study emphasizes the need to intervene in both bone marrow and peripheral responses to facilitate B cell recovery during acute HIV-1 infection.

Kaposi Sarcoma of the eyelid as an initial manifestation of AIDS.

Kaposi sarcoma (KS) is a multifocal systemic disease that originates in the vascular endothelium related to Human Herpes Virus 8 (HHV-8). In the early 1980s the first series of cases of disseminated Kaposi Sarcoma in HIV infected patients were reported. However, with the advent of highly active antiretroviral therapy (HAART) since 1997, these cases are less frequently observed by clinicians. We report the case of a 40-year-old woman, presenting with two asymptomatic purpuric nodules localized in the superior and inferior left eyelids, occluding the palpebral fissure, which were present for 4 months prior to presentation. The eyelid nodules were determined to represent KS, but there were no additional cutaneous lesions. Pulmonary and gastric KS involvement was documented. Antiretroviral therapy was initiated along with pegylated liposomal doxorubicin. The nodules gradually disappeared and her immune status eventually improved. Ocular and periorbital involvement of KS associated with HIV-1 infection as the initial clinical manifestations is a rare advent. This case is important as it illustrates that disseminated KS was not to be predicted by the number or the extension of cutaneous lesions.

A case of imported neurocysticercosis in Portugal.

Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in resource-poor countries. We report the case of a 24-year-old woman born and residing in Guinea-Bissau, who was transferred to Portugal two months after the onset of a possible meningitis (fever, headache, seizures, and coma) that did not respond to antibiotic treatment. The diagnosis of NCC was confirmed by MR imaging, which showed multiple lesions compatible with cysticercus, and by polymerase chain reaction (PCR) of the cerebrospinal fluid. After 28 days on albendazole and dexamethasone without improvement, she was started on praziquantel, which she completed in six weeks with progressive recovery.

Hypovitaminosis D in HIV-infected patients in Lisbon: a link with antiretroviral treatment.

INTRODUCTION: Recent data indicates that low vitamin D (25(OH)D) levels can lead to a worst prognosis in HIV-infected individuals, even in those on successful antiretroviral therapy (ART) [1]. Portugal is the European country that has the largest average sun exposure time but prevalence of hypovitaminosis D is mostly unknown. Our aim was to determine the prevalence of hypovitaminosis D in HIV patients in Lisbon and the possible association with ART. METHODS: From 2012 to January 2014, plasma samples from 518 HIV-infected patients were collected to 25(OH)D levels determination. Data on demographic features (age, ethnicity, country of origin) and clinical/laboratory parameters were collected from clinical files (HIV subtype, CD4+ cell count, CD4+ nadir, viral load (VL), HBV/HCV co-infection and ART). 25(OH)D status was defined as: deficiency <20 ng/mL, insufficiency 20-30 ng/mL, optimal >30 ng/mL. RESULTS: Median age was 46 years old (±11); 62.0% (321/518) were male; 81.3% (421/518) were Caucasian and 78.6% (407/518) were Portuguese. Most patients (96.1%; 498/518), were HIV-1 infected, 22.9% (114/498) and 4.0% (20/498) of them were HCV and/or HBV co-infected, respectively. Mean CD4+ cell count was 648 cells/µL (±333) and nadir was 219 cells/µL (±179). On treated patients VL was <40 HIV RNA/mL in 86.7% (417/481). The median levels of 25(OH)D was 20.0 ng/mL (range 4.1-99.7) and we found differences between values observed during Winter (median 16.7 ng/mL) and Summer (median 24.9 ng/mL) (p<0.0001). Low 25(OH)D levels were not correlated to ethnicity (p=0.066). 25(OH)D level was <30 ng/mL in 80.1% (415/518) of the patients, from which 30.9% (160/518) and 49.2% (255/518) had insufficiency and deficiency levels, respectively. Most (92.9%; 481/518) were on ART: regimens containing PI (47.5%), NNRTI (40.3%; 41.3% on NVP and 58.7% on EFV), II (1.2%), PI+NNRTI (3.9%). Comparing the 25(OH)D level along the different ART regimens (PI vs NVP; PI vs EFV; PI vs no ART) there were differences between PI and EFV (p=0.044). CONCLUSIONS: In this study, 80.1% of the HIV-infected patients had hypovitaminosis D and ART regimens with EFV were more often associated with low 25(OH)D levels. Understanding the impact of the different antiretroviral drugs on 25(OH)D status could help to decide in clinical practice whether 25(OH)D supplementation or drug switch are the best options for each patient.

Acute Q fever in Portugal. Epidemiological and clinical features of 32 hospitalized patients.

INTRODUCTION: Q fever is a worldwide zoonosis caused by Coxiella burnetii. The main characteristic of acute Q fever is its clinical polymorphism, usually presenting as a febrile illness with varying degrees of hepatitis and/or pneumonia. Q fever is endemic in Portugal, and it is an obligatory notifiable disease since 1999. However, its epidemiological and clinical characteristics are still incompletely described. METHODS: We performed a retrospective study of 32 cases admitted in the Infectious Diseases Department, Santa Maria's University Hospital, from January 2001 to December 2010, in whom acute Q fever was diagnosed by the presence of antibodies to phase II Coxiella burnetii antigens associated with a compatible clinical syndrome. RESULTS: Out of the 32 cases recorded, 29 (91%) were male, with a male:female ratio of 9.7:1. Individuals at productive age were mainly affected (88%, n=28, with ages between 25 and 64 years). Clinically, the most common manifestation of acute Q fever was hepatic involvement (84%, n=27), which occurred isolated in 53% (n=17) of the cases. Hepatitis was more severe, presenting with higher values of liver function tests, in patients presenting both pulmonary and hepatic involvement. Additionally, we report one case of myocarditis and another one with neurological involvement. Empiric but appropriate antibiotic therapy was given in 66% (n=21) of the cases. There was a complete recovery in 94% (n=30) of the patients, and one death. We confirmed the sub-notification of this disease in Portugal, with only 47% (n=15) of the cases notified. CONCLUSION: In Portugal further studies are needed to confirm our results. From the 32 cases studied, acute Q fever presented more frequently as a febrile disease with hepatic involvement affecting mainly young male individuals. Furthermore, acute Q fever is clearly underdiagnosed and underreported in Portugal, which suggests that an increased awareness of the disease is needed, together with a broader use of serological testing.