RESUMEN
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
Pharmacologic inhibition of the mammalian target of rapamycin (mTOR) in the setting of renal transplantation has previously been associated with lower human immunodeficiency virus 1 (HIV-1) DNA burden, and in vitro studies suggest that mTOR inhibition may lead to HIV transcriptional silencing. Because prospective clinical trials are lacking, we conducted an open-label, single-arm study to determine the impact of the broad mTOR inhibitor, everolimus, on residual HIV burden, transcriptional gene expression profiles, and immune responses in HIV-infected adult solid organ transplant (SOT) recipients on antiretroviral therapy. Whereas everolimus therapy did not have an overall effect on cell-associated HIV-1 DNA and RNA levels in the entire cohort, participants who maintained everolimus time-averaged trough levels >5 ng/mL during the first 2 months of therapy had significantly lower RNA levels up to 6 months after the cessation of study drug. Time-averaged everolimus trough levels significantly correlated with greater inhibition of mTOR gene pathway transcriptional activity. Everolimus treatment also led to decreased PD-1 expression on certain T cell subsets. These data support the rationale for further study of the effects of mTOR inhibition on HIV transcriptional silencing in non-SOT populations, either alone or in combination with other strategies. Trial Registration: ClinicalTrials.gov NCT02429869.
Asunto(s)
Trasplante de Órganos , Preparaciones Farmacéuticas , Adulto , Everolimus/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Diana Mecanicista del Complejo 1 de la Rapamicina , Estudios ProspectivosRESUMEN
Kidney transplant (KT) outcomes for HIV-infected (HIV+) persons are excellent, yet acute rejection (AR) is common and optimal immunosuppressive regimens remain unclear. Early steroid withdrawal (ESW) is associated with AR in other populations, but its utilization and impact are unknown in HIV+ KT. Using SRTR, we identified 1225 HIV+ KT recipients between January 1, 2000, and December 31, 2017, without AR, graft failure, or mortality during KT admission, and compared those with ESW with those with steroid continuation (SC). We quantified associations between ESW and AR using multivariable logistic regression and interval-censored survival analysis, as well as with graft failure and mortality using Cox regression, adjusting for donor, recipient, and immunologic factors. ESW utilization was 20.4%, with more zero HLA mismatch (8% vs 4%), living donors (26% vs 20%), and lymphodepleting induction (64% vs 46%) compared to the SC group. ESW utilization varied widely across 129 centers, with less use at high- versus moderate-volume centers (6% vs 21%, P < .001). AR was more common with ESW by 1 year (18.4% vs 12.3%; aOR: 1.08 1.612.41 , P = .04) and over the study period (aHR: 1.02 1.391.90 , P = .03), without difference in death-censored graft failure (aHR 0.60 0.911.36 , P = .33) or mortality (aHR: 0.75 1.151.77 , P = .45). To reduce AR after HIV+ KT, tailoring of ESW utilization is reasonable.
Asunto(s)
Infecciones por VIH , Trasplante de Riñón , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunosupresores , Trasplante de Riñón/efectos adversos , Esteroides , 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
The approach to transplantation in human immunodeficiency virus (HIV)-positive patients has been conservative due to fear of exacerbating an immunocompromised condition. As a result, HIV-positive patients with diabetes were initially excluded from beta cell replacement therapy. Early reports of pancreas transplant in patients with HIV described high rates of early graft loss with limited follow-up. We report long-term follow-up of islet or pancreas transplantation in HIV-positive type 1 diabetic patients who received a kidney transplant concurrently or had previously undergone kidney transplantation. Although 4 patients developed polyoma viremia, highly active antiretroviral therapy and adequate infectious prophylaxis were successful in providing protection until CD4+ counts recovered. Coordination with HIV providers is critical to reduce the risk of rejection by minimizing drug-drug interactions. Also, protocols for prophylaxis of opportunistic infections and strategies for monitoring and treating BK viremia are important given the degree of immunosuppression required. This series demonstrates that type 1 diabetic patients with well-controlled HIV and renal failure can be appropriate candidates for beta cell replacement, with a low rate of infectious complications, early graft loss, and rejection, so excellent long-term graft survival is possible. Additionally, patients with HIV and cardiovascular contraindications can undergo islet infusion.
Asunto(s)
Diabetes Mellitus Tipo 1 , Infecciones por VIH , Seropositividad para VIH , Trasplante de Páncreas , Insuficiencia Renal , Diabetes Mellitus Tipo 1/complicaciones , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Trasplante de Páncreas/efectos adversosRESUMEN
We compared access to a kidney transplantation (KT) waiting list (WL) and to KT between people living with HIV (PLHIV) and HIV-uninfected controls. Using the REIN (the national Renal Epidemiology and Information Network registry), we included all PLHIV initiating dialysis in France throughout 2006-2010 and HIV-uninfected controls matched for age, sex, year of dialysis initiation, and the existence of a diabetic nephropathy. Patients were prospectively followed until December 2015. We used a competitive risk approach to assess the cumulative incidence of enrollment on WL and of KT, with death as a competing event (subdistribution hazard ratio adjusted on comorbidities, asdHR). There were 255 PLHIV in the REIN (median age 47 years) of whom 180 (71%) were also found in the French Hospital Database on HIV (FHDH-ANRS CO4) including 126 (70%) known to be on antiretroviral therapy with HIV viral suppression (VS). Five years after dialysis initiation, 65%, and 76%, of treated PLHIV with VS, and of HIV-uninfected controls were enrolled on a WL (asdHR 0.68; 95% CI 0.50-0.91). Access to KT was also less frequent and delayed for treated PLHIV with VS (asdHR 0.75, 95% CI, 0.52-1.10). PLHIV continue to face difficulties to access KT.
Asunto(s)
Acceso a la Información , Infecciones por VIH/complicaciones , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Trasplante de Riñón/estadística & datos numéricos , Diálisis Renal , Listas de Espera/mortalidad , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , VIH/aislamiento & purificación , Accesibilidad a los Servicios de Salud/normas , Disparidades en Atención de Salud/normas , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Tasa de SupervivenciaRESUMEN
The HIV Organ Policy Equity (HOPE) Act, enacted on November 21, 2013, enables research on the transplantation of organs from donors infected with human immunodeficiency virus (HIV) (HIV+) into HIV+ individuals who, prior to transplantation, are infected with HIV. In 2015, the Organ Procurement and Transplantation Network revised organ allocation policies on November 21, and on November 23, the Secretary of Health and Human Services published research criteria and revised the Final Rule accordingly. The HOPE Act appears to be underutilized to date. As of December 31, 2018, there were 56 donors recovered (50 donors transplanted) resulting in 102 organs transplanted (31 liver, 71 kidney). As of December 31, 2018, 212 registrations were indicated on the waiting list as willing to accept an HIV+ kidney or liver, most of which were waiting in active status. Due to the limited number of transplants performed to date, definitive safety conclusions cannot be reached at this time, though current data suggest that 1-year patient and graft survival does not deviate in a major way from that observed in HIV+ recipients of non-HIV+ organs or non-HIV+ recipients. As safety data are reviewed and disseminated, it is anticipated that HOPE participation will increase should safety signals remain low.
Asunto(s)
Infecciones por VIH/transmisión , Trasplante de Órganos/legislación & jurisprudencia , Trasplante de Órganos/normas , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/normas , Adulto , Femenino , Supervivencia de Injerto , Infecciones por VIH/epidemiología , Política de Salud , Humanos , Riñón/virología , Trasplante de Riñón , Hígado/virología , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Sistema de Registros , Donantes de Tejidos , Resultado del Tratamiento , Estados Unidos/epidemiología , Listas de Espera , Adulto JovenRESUMEN
Human immunodeficiency virus-positive (HIV+) patients are not routinely offered heart transplantation (HT) due to lack of adequate outcomes data. Between January 2004 and March 2017, we identified 41 adult (≥18 years) HT recipients with known HIV+ serostatus at the time of transplant in UNOS and evaluated post-HT outcomes. Overall, Kaplan-Meier (KM) estimates of survival at 1 and 5 years were 85.9% and 77.3%, respectively, with no significant difference in bridge-to-transplant ventricular-assist device (BTT-VAD, n = 22) and no-BTT-VAD (n = 19). KM estimates of cardiac allograft vasculopathy (CAV) and malignancy at 5 years were 32% and 19%, respectively. Using propensity scores, 41 HIV+ HT recipients were matched to 41 HIV- HT recipients for idiopathic dilated-cardiomyopathy; and there was no significant difference in post-HT survival up to 5 years. Furthermore, only 24 centers in the United States had performed HIV+ HT during the study period, indicating that >80% of HT centers in the United States had not performed any HIV+ HT. In a cohort representative of the current status of HIV+ HTs in the United States, we found that the posttransplant survival was excellent and rates of CAV and malignancy were comparable to the overall HT population. These results should encourage greater number of centers to offer HT to suitable HIV+ candidates and help reduce unequal access to HT for HIV+ patients.
Asunto(s)
Cardiomiopatía Dilatada/mortalidad , Rechazo de Injerto/mortalidad , Infecciones por VIH/complicaciones , Insuficiencia Cardíaca/terapia , Trasplante de Corazón/mortalidad , Complicaciones Posoperatorias/mortalidad , Enfermedades Vasculares/mortalidad , Adulto , Aloinjertos , Cardiomiopatía Dilatada/epidemiología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , VIH/aislamiento & purificación , Infecciones por VIH/virología , Insuficiencia Cardíaca/etiología , Trasplante de Corazón/efectos adversos , Corazón Auxiliar/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , New York/epidemiología , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Enfermedades Vasculares/epidemiologíaRESUMEN
Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely.