RESUMEN
BACKGROUND: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).
Asunto(s)
Infección Irruptiva , Infecciones por VIH , Fallo Renal Crónico , Trasplante de Riñón , Donantes de Tejidos , Obtención de Tejidos y Órganos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infección Irruptiva/epidemiología , Infección Irruptiva/inmunología , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Obtención de Tejidos y Órganos/métodos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapiaRESUMEN
BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.
Asunto(s)
Infecciones por VIH , Seropositividad para VIH , Antirretrovirales/uso terapéutico , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Seropositividad para VIH/tratamiento farmacológico , Humanos , Integrasas , Estudios Prospectivos , Donantes de Tejidos , Estados Unidos/epidemiología , Carga ViralRESUMEN
Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.
Asunto(s)
Infecciones por VIH , Hepatitis C , Trasplante de Hígado , Estudios de Seguimiento , Supervivencia de Injerto , Infecciones por VIH/complicaciones , Humanos , Trasplante de Hígado/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Donantes de TejidosRESUMEN
In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI); however, guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss the current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.
Asunto(s)
Infecciones por Clostridium , Trasplante de Microbiota Fecal , Trasplante de Órganos , Receptores de Trasplantes , Clostridioides difficile , Infecciones por Clostridium/etiología , Infecciones por Clostridium/prevención & control , Selección de Donante , Trasplante de Microbiota Fecal/métodos , Humanos , Trasplante de Órganos/efectos adversos , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, Pâ <â .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, Pâ =â .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, Pâ =â .018], obesity [aOR 1.9, 95% CI 1.0-3.4, Pâ =â .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, Pâ =â .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, Pâ =â .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.
Asunto(s)
COVID-19 , Trasplante de Órganos , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Órganos/efectos adversos , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.
Asunto(s)
Infecciones por VIH , Trasplante de Riñón , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones por VIH/complicaciones , Humanos , Proyectos Piloto , Estudios Prospectivos , Factores de Riesgo , Donantes de TejidosRESUMEN
Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.
Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/métodos , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes/estadística & datos numéricos , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/microbiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.
Asunto(s)
Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Inmunosupresores/sangre , Trasplante de Órganos/efectos adversos , Tacrolimus/sangre , Humanos , Inmunosupresores/farmacocinética , Estudios Retrospectivos , Tacrolimus/farmacocinéticaRESUMEN
BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients represent a high-risk group for developing Clostridium difficile (CD) infection (CDI). We aimed to identify specific risk factors for CDI in an HSCT patient population during the peritransplant period. METHODS: We performed a case-control study within a cohort of HSCT patients who received a transplant from November 2010 to March 2013. Cases had a clinical presentation compatible with CDI and a positive stool sample Xpert® C. difficile test. Controls were CDI negative and matched on age, gender, and transplant type. Peritransplant period was defined as -30 days or time of stem cell mobilization maneuver to 30 days post transplant in autologous SCT or 90 days post transplant in allogeneic SCT. RESULTS: Of 781 HSCTs performed during the study period, 650 (83.2%) had a stool sample submitted for CD testing. Eight-six (13.2%) cases with CDI were identified. Most of the cases were diagnosed within a week after transplantation (median of 5 days). In adjusted analysis, prior hospitalization (odds ratio [OR]: 2.01, 95% confidence interval [CI] 1.2-3.36), prior cephalosporin administration (OR 2.72, 95% CI: 1.54-4.83), and prior chemotherapy (OR: 3.26, 95% CI: 1.92-5.5) were significantly associated with CDI. CONCLUSIONS: Hospitalization, and prior antibiotic and chemotherapy use are risk factors that are not easily modifiable, which emphasizes the need to start investigating preventive or prophylactic strategies in this high-risk population.
Asunto(s)
Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Antibacterianos/administración & dosificación , Estudios de Casos y Controles , Cefalosporinas/administración & dosificación , Infecciones por Clostridium/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. METHODS: We report two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. RESULTS: While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. CONCLUSIONS: It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
Asunto(s)
Anticuerpos Antivirales/uso terapéutico , Fiebre Hemorrágica Ebola/terapia , ARN Interferente Pequeño/uso terapéutico , Adulto , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.
Asunto(s)
Infecciones por VIH , Trasplante de Riñón , Humanos , Masculino , Listas de Espera , Riñón , Donantes de Tejidos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Receptores de Trasplantes , Infecciones por VIH/diagnósticoRESUMEN
Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum ß-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.
Asunto(s)
Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Humanos , Trasplante de Microbiota Fecal/efectos adversos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Heces/microbiología , Resultado del TratamientoRESUMEN
Bacillary peliosis hepatis is a well recognised manifestation of disseminated Bartonella henselae infection that can occur in immunocompromised individuals. Haemophagocytic lymphohistiocytosis is an immune-mediated condition with features that can overlap with a severe primary infection such as disseminated Bartonella spp infection. We report a case of bacillary peliosis hepatis and secondary haemophagocytic lymphohistiocytosis due to disseminated Bartonella spp infection in a kidney-transplant recipient with well controlled HIV. The patient reported 2 weeks of fever and abdominal pain and was found to have hepatomegaly. He recalled exposure to a sick dog but reported no cat exposures. Laboratory evaluation was notable for pancytopenia and cholestatic injury. The patient met more than five of eight clinical criteria for haemophagocytic lymphohistiocytosis. Pathology review of a bone marrow core biopsy identified haemophagocytosis. A transjugular liver biopsy was done, and histopathology review identified peliosis hepatis. Warthin-Starry staining of the bone marrow showed pleiomorphic coccobacillary organisms. The B henselae IgG titre was 1:512, and Bartonella-specific DNA targets were detected by peripheral blood PCR. Treatment with doxycycline, increased prednisone, and pausing the mycophenolate component of his transplant immunosuppression regimen resulted in an excellent clinical response. Secondary haemophagocytic lymphohistiocytosis can be difficult to distinguish from severe systemic infection. A high index of suspicion can support the diagnosis of systemic Bartonella spp infection in those who present with haemophagocytic lymphohistiocytosis, especially in patients with hepatomegaly, immunosuppression, and germane animal exposures.
Asunto(s)
Angiomatosis Bacilar , Infecciones por Bartonella , Bartonella henselae , Bartonella , Infecciones por VIH , Trasplante de Riñón , Linfohistiocitosis Hemofagocítica , Peliosis Hepática , Angiomatosis Bacilar/complicaciones , Animales , Infecciones por Bartonella/complicaciones , Infecciones por Bartonella/diagnóstico , Infecciones por Bartonella/patología , Bartonella henselae/genética , Perros , Doxiciclina/uso terapéutico , Infecciones por VIH/complicaciones , Hepatomegalia/complicaciones , Inmunoglobulina G , Trasplante de Riñón/efectos adversos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Masculino , Peliosis Hepática/complicaciones , Peliosis Hepática/patología , Peliosis Hepática/veterinaria , PrednisonaRESUMEN
The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRß repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRß clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.
Asunto(s)
Infecciones por VIH , VIH-1 , Trasplante de Riñón , Humanos , VIH-1/genética , Infecciones por VIH/tratamiento farmacológico , Latencia del Virus , Provirus/genética , Terapia de Inmunosupresión , Receptores de Antígenos de Linfocitos TRESUMEN
BACKGROUND: One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection. METHODS: In this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per µL for liver and >200 cells per µL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262. FINDINGS: 14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2â080â000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART. INTERPRETATION: These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute.
Asunto(s)
Seropositividad para VIH/epidemiología , Trasplante de Riñón , Trasplante de Hígado , Sobreinfección/epidemiología , Sobreinfección/etiología , Anciano , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Femenino , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/inmunología , Seropositividad para VIH/virología , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Filogenia , Estudios Prospectivos , Análisis de Secuencia de ADN , Sobreinfección/diagnóstico , Carga Viral , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
INTRODUCTION: Enterococcus faecium is a commensal organism commonly colonizing the human gastrointestinal tract. Although it is generally a non-virulent organism, E. faecium can cause significant morbidity and mortality due to its inherent and acquired resistances to commonly used antimicrobials. Patients who are immunosuppressed are particularly vulnerable. CASE PRESENTATION: A 65-75-year-old patient with a history of an orthotopic liver transplant for hepatitis C infection and diabetes was re-admitted to the hospital with abdominal pain and fever. The patient had several recent admissions related to the presentation reported here, which included treatment with a prolonged course of broad-spectrum antibiotics. The patient was found to have a recurrent liver abscess and blood cultures grew vancomycin-resistant E. faecium, non-susceptible to all tested agents: ampicillin, penicillin, vancomycin, daptomycin and linezolid. The patient was started initially on chloramphenicol intravenously while awaiting additional susceptibility testing, which ultimately revealed chloramphenicol non-susceptibility. Tigecycline was started but the patient ultimately decided to pursue hospice care. CONCLUSION: Multi-drug-resistant organisms are increasingly being recognized and are associated with poorer outcomes, particularly in immunosuppressed patients. We describe a particularly resistant organism and discuss potential therapeutic options.
RESUMEN
Left ventricular assist device infections (LVADIs) are common but challenging to treat, often requiring prolonged courses of intravenous antibiotics. Dalbavancin could have a role in treating patients with chronic LVADIs given its less frequent dosing requirements. Here, we illustrate a case in which dalbavancin was used as suppressive therapy for an LVADI for greater than 7 months.