Background: Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods: To address this issue we analyzed CD4⁺ T absolute counts and the proportion of CD8⁺ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results: We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4⁺ T cell counts under 200 cells/mm³, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm³). Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4⁺ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8⁺ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions: Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4⁺ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR. These data suggest CD38 expression in CD8+ T cells interesting tool identifying HIV/leprosy individuals at risk for IRIS/RR. So, a comparative investigation to leprosy patients at RR should be conducted.

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1βrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

Background: Severe COVID-19 presents a variety of clinical manifestations associated with inflammatory profiles. People living with HIV (PLWH) could face a higher risk of hospitalization and mortality from COVID-19, depending on their immunosuppression levels. This study describes inflammatory markers in COVID-19 clinical outcomes with and without HIV infection. Methods: We analyzed 112 inpatients of the Hospital Center for COVID-19 (INI/FIOCRUZ), including 22 cases of COVID-19 in PLWH (COVID/PLWH group). Plasma samples were tested for a panel of 15 cytokines by Luminex. Sociodemographic, clinical, and laboratory data were collected from patients’ clinical records. Results: COVID-19 individuals were stratified according to the WHO clinical severity profiles at hospitalization. Significant differences in clinical scores, symptoms (coughs), and the occurrence of HIV infection were found among the groups. Clinical blood parameters and plasma cytokines were analyzed among COVID-19 groups with distinct severity profiles. Critical COVID-19 cases showed higher levels of inflammatory markers (Bilirubin, D-dimer, PCR, and urea, as well as IL-8, IL-10, TNF-α, INF-α, IL-1β, IL-17A, IL-23, IL-6) than moderate and severe groups. The COVID/PLWH group had lower CD4 counts (64 cells/mm³) and cytokine levels than other COVID-19 patients. Conclusions: Overall, critically ill COVID-19 patients exhibited heightened inflammatory responses, while COVID/PLWH demonstrated unique immunological characteristics without increased mortality risk.

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm³. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm³. We observed a negative correlation between the pre-vaccination level of CD8⁺ T cell exhaustion and CD4⁺ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

Background: Severe COVID-19 presents a variety of clinical manifestations associated with inflammatory profiles. People living with HIV (PLWH) could face a higher risk of hospitalization and mortality from COVID-19, depending on their immunosuppression levels. This study describes inflammatory markers in COVID-19 clinical outcomes with and without HIV. Methods: We analyzed 112 inpatients of the Hospital Center for COVID-19 (INI/FIOCRUZ), including 22 cases of COVID-19 in PLWH (COVID/PLWH group). Plasma samples were tested for a panel of 15 cytokines by Luminex. Sociodemographic, clinical, and laboratory data were collected from patients’ clinical records. Results: COVID-19 individuals were stratified according to the WHO clinical severity profiles at hospitalization. Significant differences in clinical scores, symptoms (coughs), and the occurrence of HIV infection were found among the groups. Clinical blood parameters and plasma cytokines were analyzed among COVID-19 groups with distinct severity profiles. Critical COVID-19 cases showed higher levels of inflammatory markers (Bilirubin, D-dimer, PCR, and urea, as well as IL-8, IL-10, TNF-α, INF-α, IL-1β, IL-17A, IL-23, IL-6) than moderate and severe groups. The COVID/PLWH group had lower CD4 counts (64 cells/mm3) and cytokine levels than other COVID-19 patients. Conclusion: Overall, critically ill COVID-19 patients exhibited heightened inflammatory responses, while COVID/PLWH demonstrated unique immunological characteristics without increased mortality risk.