RESUMEN
The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.
Asunto(s)
Microbioma Gastrointestinal , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Boca/microbiología , Índice de Masa Corporal , Heces/microbiología , Antirretrovirales/uso terapéutico , Saliva/microbiologíaRESUMEN
Mucosa-associated invariant T (MAIT) cells are unconventional T cells with innate-like capacity to rapidly respond to microbial infection via MR1-restricted antigen recognition. Emerging evidence indicate that they can also act as rapid sensors of viral infection via innate cytokine activation. However, their possible role in the immune response to mRNA vaccination is unknown. Here, we evaluated the involvement of MAIT cells in individuals vaccinated with the BNT162b2 mRNA SARS-CoV-2 vaccine. MAIT cell levels, phenotype and function in circulation were preserved and unperturbed through day 35 post-vaccination in healthy donor (HD) vaccinees, as well as people living with HIV (PLWH) or with primary immunodeficiency (PID). Unexpectedly, pre-vaccination and post-vaccination levels of MAIT cells correlated positively with the magnitude of the SARS-CoV-2 spike protein-specific CD4 T cell and antibody responses in the HD vaccinees. This pattern was largely preserved in the PID group, but less so in the PLWH group. Furthermore, in the HD vaccinees levels of MAIT cell activation and cytolytic potential correlated negatively to the adaptive antigen-specific immune responses. These findings indicate an unexpected association between MAIT cell compartment characteristics and the immune response magnitude to the BNT162b2 mRNA vaccine.
Asunto(s)
COVID-19 , Células T Invariantes Asociadas a Mucosa , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunidad Humoral , ARN Mensajero/genética , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
People living with HIV (PLHIV) have an increased risk of hematologic malignancies (HMs). We aimed to characterize HMs among PLHIV at Karolinska University Hospital, Stockholm, Sweden. We studied all PLHIV receiving care at our center between 2004 and 2018. Data were retrieved retrospectively from InfCareHIV database and medical records. Around 3,484 patients received HIV care for a total of 22,903 person-years (py) with median follow-up of 7.6 years. HMs were identified in 43 patients with 30 cases of non-Hodgkin lymphoma (NHL), 9 cases of Hodgkin lymphoma (HL), 2 multicentric Castleman's disease, and 1 case each of myeloma and myelodysplastic syndrome. The incidence rate of NHL was 88/105 py and HL 39.6/105 py. The incidence of NHL declined 2004-2010 versus 2011-2018 (180.8 vs. 40.1/105 py; p = .001). Median time from HIV diagnosis to malignancy was shorter in NHL compared with HL (1.2 years vs. 8.9 years; p = .01) and effective HIV treatment was less common in NHL (33% vs. 100%; p < .001). The 5-year survival rate of NHL was 59% and HL 43%, significantly lower compared with lymphoma survival in the general population in Sweden. In the era of effective antiretroviral therapy (ART), the incidence rate of lymphoma was more than five times higher in PLHIV and 5-year survival significantly inferior. Efforts for earlier identification of HIV-infected individuals are likely to affect the incidence of NHL. Additionally, an effective screening for clinical and laboratory signs of HL in PLHIV on ART should be introduced to improve identification and survival of HL in this population.