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1.
BMJ Case Rep ; 13(11)2020 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-33148591

RESUMEN

A 59-year-old Caucasian man infected with HIV, in remission from human herpes virus-8-positive extracavitary primary effusion lymphoma (EC-PEL), presented to a sexual health clinic with fever and rectal pain 10 weeks after a single episode of receptive anal sexual intercourse with another man. He was initially treated for a presumptive diagnosis of lymphogranuloma venereum proctitis, then for syphilis on positive serology. Rectosigmoidoscopy revealed a single ulcerated rectal mass; endoscopic biopsies confirmed the recurrence of EC-PEL. The patient received chemotherapy and went into remission. This is the first reported case of EC-PEL occurring synchronously with early syphilis, and specifically at the site of inoculation, which can be a major diagnostic challenge since both conditions may present with lymphadenopathy, mucosal involvement and constitutional symptoms. We reviewed the literature for similar cases and hypothesised that syphilis may have triggered the recurrence of this rare lymphoma.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33184634

RESUMEN

OBJECTIVES: The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. METHODS: Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. RESULTS: R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. CONCLUSIONS: Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.

3.
Front Immunol ; 11: 583820, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33101312

RESUMEN

Antibody dependent (AD) functions such as AD cellular cytotoxicity (ADCC) were associated with lower viral load (VL) in untreated HIV progressors and protection from HIV infection in the modestly protective RV144 HIV vaccine trial. Target cells used to measure ADCC, AD complement deposition (ADCD), and AD cellular trogocytosis (ADCT) have been either HIV envelope (Env) gp120-coated CEM.NKr.CCR5 cells or HIV infected cell cultures. In HIV infected cell cultures, uninfected bystander cells take up gp120 shed from infected cells. Both gp120-coated and gp120+ bystander cells expose CD4 induced (CD4i) epitopes, which are normally hidden in native trimeric Env expressed by genuinely HIV infected cells since Nef and Vpu downmodulate cell surface CD4. Antibody dependent assays using either of these target cells probe for CD4i Abs that are abundant in HIV+ plasma but that do not recognize HIV-infected cells. Here, we examined ADCC, ADCD, and ADCT functions using a target cell line, sorted HIV-infected cell line cells, whose HIV infection frequency nears 100% and that expresses HIV Env in a native trimeric closed conformation. Using sorted HIV-infected cells (siCEM) as targets, we probed the binding and AD functions of anti-gp120/Env Abs in plasma from HIV-infected untreated progressor (UTP, n = 18) and treated (TP, n = 24) subjects, compared to that in Elite controllers (EC, n = 37) and Viral Controllers (VC, n = 16), which are rare subsets of HIV-infected individuals who maintain undetectable or low VL, respectively, without treatment. Gp120-coated beads were used to measure AD cellular phagocytosis. Equivalent concentrations of input IgG in plasma from UTPs, ECs, and VCs supported higher levels of all AD functions tested than plasma from TPs. When AD activities were normalized to the concentration of anti-gp120/Env-specific Abs, between-group differences largely disappeared. This finding suggests that the anti-gp120/Env Abs concentrations and not their potency determined AD functional levels in these assays. Elite controllers did differ from the other groups by having AD functions that were highly polyfunctional and highly correlated with each other. PCR measurement of HIV reservoir size showed that ADCC activity was higher in ECs and VCs with a reservoir size below the limit of detection compared to those having a measurable HIV reservoir size.

4.
Front Immunol ; 11: 570063, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33072111

RESUMEN

Coronavirus disease 2019 (COVID-19) is a pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most infected people have mild or moderate symptoms and recover without the need for extensive treatment. However, for seriously ill patients, no specific treatments are currently available. Convalescent plasma therapy (CPT), a passive immunotherapy, involves infusing plasma from recovered people into actively infected people, and is thought to be a specific intervention to improve outcome in patients with severe COVID-19. The presumed mechanism involves neutralizing antibodies and antibody dependent cytotoxicity/phagocytosis. Previous CPT trials showed an effect in SARS and pilot studies suggest CPT is an effective and safe strategy for seriously ill COVID-19 patients. CPT is currently being tested in large randomized clinical trials. Herein, we critically review the mechanism, applications and the challenges for CPT in the treatment of severe COVID-19, paving the way toward vaccine and immunotherapy development.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Betacoronavirus/inmunología , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Humanos , Inmunización Pasiva , Plasma/inmunología , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
mBio ; 11(5)2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32994328

RESUMEN

Macrophages are a target of human immunodeficiency virus type 1 (HIV-1) and may serve as a viral reservoir during antiretroviral therapy (ART). Their susceptibility to HIV-1 infection is subject to variations from permissiveness to resistance depending on their origin, tissue localization, and polarization profile. This is in part due to the expression of regulatory microRNAs. Here, we identify two microRNA paralogs, microRNA 103 (miR-103) and miR-107, as regulators of CCR5 expression that are upregulated in noninfected bystander cells of HIV-1-infected-monocyte-derived macrophage (MDM) cultures. Transfection of microRNA 103 mimics in MDMs reduced CCR5 expression levels and inhibited CCR5-dependent HIV-1 entry, whereas the corresponding antagomirs enhanced virus spread in HIV-infected MDMs. Treatment of MDMs with interleukin-1ß (IL-1ß) enhanced microRNA 103 expression, a condition that we found contributed to the reduction of CCR5 mRNA in IL-1ß-exposed MDMs. Interestingly, we show that the induction of miR-103/107 expression is part of a tumor suppressor p53 response triggered by secreted IL-1ß that renders macrophages refractory to HIV-1 entry. In a more physiological context, the levels of microRNAs 103 and 107 were found enriched in tissue-resident colon macrophages of healthy donors and alveolar macrophages of individuals under antiretroviral therapy, conceivably contributing to their relative resistance to HIV-1 infection. Overall, these findings highlight the role of p53 in enforcing proinflammatory antiviral responses in macrophages, at least in part, through miR-103/107-mediated downmodulation of CCR5 expression and HIV-1 entry.IMPORTANCE Macrophages are heterogeneous immune cells that display varying susceptibilities to HIV-1 infection, in part due to the expression of small noncoding microRNAs involved in the posttranscriptional regulation of gene expression and silencing. Here, we identify microRNAs 103 and 107 as important p53-regulated effectors of the antiviral response triggered by the proinflammatory cytokine IL-1ß in macrophages. These microRNAs, which are enriched in colon macrophages of healthy donors and alveolar macrophages of HIV-infected individuals under antiretroviral therapy, act as inhibitors of HIV-1 entry through their capacity to downregulate the CCR5 coreceptor. These results highlight the important role played by miR-103/107 in modulating CCR5 expression and HIV-1 entry in macrophages. They further underscore a distinct function of the tumor suppressor p53 in enforcing proinflammatory antiviral responses in macrophages, thus providing insight into a cellular pathway that could be targeted to limit the establishment of viral reservoirs in these cells.

6.
Open Forum Infect Dis ; 7(9): ofaa338, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32964062

RESUMEN

Background: People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PWH receiving ART, especially those with a low CD4/CD8 ratio. Methods: In the Lilac pilot trial, we recruited 23 nondiabetic PWH receiving ART for more than 2 years with a low CD4/CD8 ratio (<0.7). Blood and stool samples were collected during study visits at baseline, after a 12-week metformin treatment, and 12 weeks after discontinuation. Microbiota composition was analyzed by 16S rDNA gene sequencing, and markers of inflammation were assessed in plasma. Results: Metformin decreased weight in PWH, and weight loss was inversely correlated with plasma levels of the satiety factor GDF-15. Furthermore, metformin changed the gut microbiota composition by increasing the abundance of anti-inflammatory bacteria such as butyrate-producing species and the protective Akkermansia muciniphila. Conclusions: Our study provides the first evidence that a 12-week metformin treatment decreased weight and favored anti-inflammatory bacteria abundance in the microbiota of nondiabetic ART-treated PWH. Larger randomized placebo-controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PWH.

7.
Mycoses ; 2020 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-32780885

RESUMEN

BACKGROUND: (1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels. METHODS: We conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8 hours after intake. RESULTS: The standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201 cells/mm3 . CONCLUSION: Our findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

8.
Nat Commun ; 11(1): 4089, 2020 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-32796830

RESUMEN

Clonal expansions occur in the persistent HIV reservoir as shown by the duplication of proviral integration sites. However, the source of the proliferation of HIV-infected cells remains unclear. Here, we analyze the TCR repertoire of single HIV-infected cells harboring translation-competent proviruses in longitudinal samples from eight individuals on antiretroviral therapy (ART). When compared to uninfected cells, the TCR repertoire of reservoir cells is heavily biased: expanded clonotypes are present in all individuals, account for the majority of reservoir cells and are often maintained over time on ART. Infected T cell clones are detected at low frequencies in the long-lived central memory compartment and overrepresented in the most differentiated memory subsets. Our results indicate that clonal expansions highly contribute to the persistence of the HIV reservoir and suggest that reservoir cells displaying a differentiated phenotype are the progeny of infected central memory cells undergoing antigen-driven clonal expansion during ART.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/genética , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Adulto , Células Cultivadas , Femenino , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/patogenicidad , Humanos , Masculino , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Carga Viral , Replicación Viral/efectos de los fármacos , Replicación Viral/genética
9.
Clin Infect Dis ; 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32756974

RESUMEN

Elite controllers (ECs) are people living with HIV who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-CMV IgG levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex and HLA type. Elevated anti-CMV titers may favor disease progression in ECs.

11.
J Immunol ; 205(3): 699-707, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32591402

RESUMEN

The success of the shock and kill strategy for the HIV cure depends both on the reactivation of the latent reservoir and on the ability of the immune system to eliminate infected cells. As latency reversal alone has not shown any impact in the size of the latent reservoir, ensuring that effector CTLs are able to recognize and kill HIV-infected cells could contribute to reservoir reduction. In this study, we investigated which functional aspects of human CTLs are associated with a better capacity to kill HIV-infected CD4+ T cells. We isolated Gag- and Nef-specific CTL clones with different TCR sequences from the PBMC of donors in acute and chronic infection. High-affinity clonotypes that showed IFN-γ production preserved even when the CD8 coreceptor was blocked, and clones with high Ag sensitivity exhibited higher efficiency at reducing the latent reservoir. Although intrinsic cytotoxic capacity did not differ according to TCR affinity, clonotypes with high TCR affinity showed a better ability to kill HIV-infected CD4+ T cells obtained from in vivo-infected PBMC and subjected to viral reactivation. Strategies aiming to specifically boost and maintain long-living memory CTLs with high TCR affinity in vivo prior to latency-reversing treatment might improve the efficacy of the shock and kill approach to reduce the latent reservoir.

13.
AIDS Care ; 32(8): 979-983, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32372653

RESUMEN

Lung cancer is the most frequent type of cancer-related death in people living with HIV (PLWH). We conducted a review of primary lung cancers in PLWH at the McGill University Health Centre from 1988-May 2018 to understand potential factors contributing to their development prior to the implementation of a lung cancer screening program. Twenty-seven individuals had a diagnosis of a lung tumor. Of these individuals, 21 (78%) had a primary lung cancer, over 21,428 person-years follow-up. Median age was 54.5 years [25th and 75th percentiles 49.0, 62.0]. Median CD4 count was 185.0 cells/µL [25th and 75th percentiles 54.0, 446.0] and 52% were on antitretroviral therapy with suppressed viral loads. Type of primary lung cancer included: non-small cell lung cancer (n = 15), small-cell lung cancer (n = 4) and bronchial carcinomas (n = 2). Metastatic disease at diagnosis was present in 11 (52%) persons. Survival was a median of 7.5 months from the time of diagnosis [25th and 75th percentiles 2.0, 9.0]. In conclusion, we observed a high proportion of lung cancers detected at very late stages of disease and with metastatic involvement. The implementation of a lung cancer screening program in 2018 should set a stage shift for earlier diagnosis and treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Infecciones por VIH/complicaciones , Neoplasias Pulmonares/diagnóstico , Recuento de Linfocito CD4 , Canadá/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Comorbilidad , Detección Precoz del Cáncer , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Neoplasias Pulmonares/epidemiología , Persona de Mediana Edad
14.
AIDS Res Ther ; 17(1): 15, 2020 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-32398104

RESUMEN

BACKGROUND: Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). Evidence in animal models have shown that markers of intestinal permeability and microbial translocation vary over the course of the day and are affected by food intake and circadian rhythms. However, daily variations of these markers are not characterized yet in PLWH. Herein, we assessed the variation of these markers over 24 h in PLWH receiving antiretroviral therapy (ART) in a well-controlled environment. METHODS: As in Canada, PLWH are predominantly men and the majority of them are now over 50 years old, we selected 11 men over 50 receiving ART with undetectable viremia for more than 3 years in this pilot study. Blood samples were collected every 4 h over 24 h before snacks/meals from 8:00 in the morning to 8:00 the next day. All participants consumed similar meals at set times, and had a comparable amount of sleep, physical exercise and light exposure. Plasma levels of bacterial lipopolysaccharide (LPS) and fungal (1→3)-ß-D-Glucan (BDG) translocation markers, along with markers of intestinal damage fatty acid binding protein (I-FABP) and regenerating islet-derived protein-3α (REG3α) were assessed by ELISA or the fungitell assay. RESULTS: Participants had a median age of 57 years old (range 50 to 63). Plasma levels of BDG and REG3α did not vary significantly over the course of the study. In contrast, a significant increase of LPS was detected between 12:00 and 16:00 (Z-score: - 1.15 ± 0.18 vs 0.16 ± 0.15, p = 0.02), and between 12:00 and 24:00 (- 1.15 ± 0.18 vs 0.89 ± 0.26, p < 0.001). The plasma levels of I-FABP at 16:00 (- 0.92 ± 0.09) were also significantly lower, compared to 8:00 the first day (0.48 ± 0.26, p = 0.002), 4:00 (0.73 ± 0.27, p < 0.001) or 8:00 on secondary day (0.88 ± 0.27, p < 0.001). CONCLUSIONS: Conversely to the fungal translocation marker BDG and the gut damage marker REG3α, time of blood collection matters for the proper evaluation for LPS and I-FABP as markers for the risk of inflammatory non-AIDS co-morbidities. These insights are instrumental for orienting clinical investigations in PLWH.

15.
AIDS ; 34(10): 1439-1449, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32310902

RESUMEN

OBJECTIVES: ATP-binding cassette (ABC) drug efflux transporters and drug metabolic enzymes could reduce antiretroviral concentrations in HIV target cells. The testis has been demonstrated to be a sanctuary site, displaying suboptimal antiretroviral concentrations and persistent HIV infection. Therefore, we compared the expression and function of ABC transporters and metabolic enzymes in CD4 and CD8 T cells isolated from human testis and peripheral blood mononuclear cells (PBMCs), and assessed their expression in circulating naive and memory CD4 T-cell phenotypes. DESIGN: Testicular tissue and blood were collected from 15 uninfected donors undergoing gender affirmation surgery. Testicular interstitial cells were isolated by enzymatic digestion, whereas PBMCs were isolated from blood by density gradient centrifugation. The expression and/or function of ABC transporters and metabolic enzymes were examined in blood and testicular T-cell subsets by flow cytometry. RESULTS: ABC transporters (P-gp, BCRP, MRP1) and metabolic enzymes (CYP3A4, UGT1A1) were expressed in testicular and circulating CD4 and CD8 T cells, as well as in circulating naive, central, transitional, and effector memory T-cell phenotypes. MRP1 demonstrated lower frequencies in T cells from testis compared with PBMCs, as well as in circulating naive T cells compared with the memory T-cell phenotypes. Functional activity of P-gp and BCRP was detected in T-cell subsets from testis and PBMCs. CONCLUSION: Our findings demonstrate for the first time that antiretroviral drug efflux transporters and metabolic enzymes are functionally expressed in T-cell subsets infiltrating the human testis. These transporters and enzymes can reduce antiretroviral intracellular concentrations, potentially contributing to residual HIV replication in the testis, and negatively impact HIV cure strategies.

16.
EBioMedicine ; 54: 102727, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32268275

RESUMEN

BACKGROUND: Untreated HIV infection leads to alterations in HIV-specific CD4+ T cells including increased expression of co-inhibitory receptors (IRs) and skewing toward a T follicular helper cell (Tfh) signature. However, which changes are maintained after suppression of viral replication with antiretroviral therapy (ART) is poorly known. METHODS: We analyzed blood CD4+ T cells specific to HIV and comparative viral antigens in ART-treated people using a cytokine-independent activation-induced marker assay alone or in combination with functional readouts. FINDINGS: In intra-individual comparisons, HIV-specific CD4+ T cells were characterized by a larger fraction of circulating Tfh (cTfh) cells than CMV- and HBV-specific cells and preferentially expressed multiple IRs and showed elevated production of the Tfh cytokines CXCL13 and IL-21. In addition, HIV-specific cTfh exhibited a predominant Th1-like phenotype and function when compared to cTfh of other specificities, contrasting with a reduction in Th1-functions in HIV-specific non-cTfh. Using longitudinal samples, we demonstrate that this distinct HIV-specific cTfh profile was induced during chronic untreated HIV infection, persisted on ART and correlated with the translation-competent HIV reservoir but not with the total HIV DNA reservoir. INTERPRETATION: Expansion and altered features of HIV-specific cTfh cells are maintained during ART and may be driven by persistent HIV antigen expression. FUNDING: This work was supported by the National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR) and the FRQS AIDS and Infectious Diseases Network.

17.
Front Immunol ; 11: 645, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32328074

RESUMEN

Gut dysbiosis, namely dysregulation of the intestinal microbiota, and increased gut permeability lead to enhanced inflammation and are commonly seen in chronic conditions such as obesity and aging. In people living with HIV (PLWH), several lines of evidence suggest that a depletion of gut CD4 T-cells is associated with gut dysbiosis, microbial translocation and systemic inflammation. Antiretroviral therapy (ART) rapidly controls viral replication, which leads to CD4 T-cell recovery and control of the disease. However, gut dysbiosis, epithelial damage and microbial translocation persist despite ART, increasing risk of developing inflammatory non-AIDS comorbidities such as cardiovascular disease, diabetes mellitus, liver steatosis and cancer. In addition to ART, an emerging research priority is to discover strategies to improve the gut microbial composition and intestinal barrier function. Probiotic interventions have been extensively used with controversial benefits in humans. Encouragingly, within the last decade, the intestinal symbiotic bacterium Akkermansia muciniphila has emerged as the "sentinel of the gut." A lower abundance of A. muciniphila has been shown in diabetic and obese people as well as in PLWH. Interventions with high levels of polyphenols such as tea or diets rich in fruit, the antibiotic vancomycin and the antidiabetic drug metformin have been shown to increase A. muciniphila abundance, contributing to improved metabolic function in diabetic and obese individuals. We hypothesize that gut microbiota rich in A. muciniphila can reduce microbial translocation and inflammation, preventing occurrences of non-AIDS comorbidities in PLWH. To this aim, we will discuss the protective effect of A. muciniphila and its potential applications, paving the way toward novel therapeutic strategies to improve gut health in PLWH.

19.
BMJ Case Rep ; 13(2)2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-32111711

RESUMEN

We report the case of a 57-year-old Caucasian woman with AIDS-related disseminated Kaposi sarcoma (KS) characterised by the combination of several unusual features. The chylous nature of the pleural effusions, the documented parietal pleural involvement at thoracoscopy and the marked clinical worsening through an immune reconstitution syndrome following antiretroviral therapy initiation represent several rare situations that occurred in the same female patient. In addition, the use of indwelling pleural catheters for dyspnoea palliation also represents a rare therapeutic intervention. This case is a reminder of the possibility of AIDS-related pleural KS, now uncommon in the era of antiretroviral therapy.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Derrame Pleural/etiología , Derrame Pleural/terapia , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Catéteres de Permanencia , Femenino , Humanos , Persona de Mediana Edad
20.
AIDS Res Ther ; 17(1): 10, 2020 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-32156291

RESUMEN

The gut microbiota is emerging as a prominent player in maintaining health through several metabolic and immune pathways. Dysregulation of gut microbiota composition, also known as dysbiosis, is involved in the clinical outcome of diabetes, inflammatory bowel diseases, cancer, aging and HIV infection. Gut dysbiosis and inflammation persist in people living with HIV (PLWH) despite receiving antiretroviral therapy, further contributing to non-AIDS comorbidities. Metformin, a widely used antidiabetic agent, has been found to benefit microbiota composition, promote gut barrier integrity and reduce inflammation in human and animal models of diabetes. Inspired by the effect of metformin on diabetes-related gut dysbiosis, we herein critically review the relevance of metformin to control inflammation in PLWH. Metformin may improve gut microbiota composition, in turn reducing inflammation and risk of non-AIDS comorbidities. This review will pave the way towards innovative strategies to counteract dysregulated microbiota and improve the lives of PLWH.

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