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Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV ⁺ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large acade...
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Context 1
... total of 58 HIV + adult kidney allograft recipients were studied (Table 1). In total, 51 subjects had at least one HIV viral load during the first year post-transplant, and except for six patients who had transient "blips" in viremia (median peak viremia, 130 copies/mL [IQR, 114-193]), all the patients had sustained ART-induced HIV viral load suppression (<50 copies/mL) post-transplant. ...
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Citations
... Los inhibidores de la integrasa no son metabolizados por la citocromo P450 o la glicoproteína P, lo que evita las interacciones farmacológicas complejas y permite su administración de forma segura en los pacientes trasplantados VIH+ (31,40,59,(71)(72)(73)(74). Es por esto que los regímenes basados en inhibidores de la integrasa son los de elección en los pacientes trasplantados VIH+ (22). ...
El trasplante renal es el tratamiento de elección en la enfermedad renal crónica terminal porque mejora la calidad de vida y la supervivencia de los pacientes al compararlo con la diálisis. Sin embargo, para mantener un injerto funcional y evitar el rechazo es necesario el uso de inmunosupresión potente durante toda la vida del injerto, lo cual puede tener como complicaciones una mayor susceptibilidad a presentar infecciones, desarrollo de cáncer, alteraciones metabólicas y problemas cardiovasculares. Los pacientes infectados con el virus de la inmunodeficiencia humana tienen alto riesgo de desarrollar enfermedad renal crónica terminal por múltiples causas. En el siglo pasado, el trasplante renal se consideraba contraindicado para estos pacientes. No obstante, hoy en día el trasplante renal se considera una opción terapéutica para pacientes adecuadamente seleccionados y con protocolos de manejo bien establecidos. Reportándose supervivencia reportadas del injerto y del paciente a tres años de 88,2 % y 82,6 % respectivamente. Este artículo de revisión tiene como objetivo revisar la experiencia mundial existente en el manejo de los pacientes trasplantados renal con infección por VIH.
... Apart from the potential for drug-drug interactions with certain ART agents, we would expect responses to treatment in PLHIV-c to be similar to those in the non-HIV population. Rejection risk improved with key developments including direct-acting antivirals that mitigate risk imposed by HCV infection [80,81], and avoidance or modification of ART regimens interacting with immunosuppressant therapy [82][83][84]. Graft survival and patient survival rates of renal transplant in HIV positive mono-infected patients are the same as in non-HIV transplant patients; studies that include HCVcoinfected patients show slightly worse survival in the pre-Direct Acting Antiviral (DAA) era [85][86][87]. This survival disadvantage has likely become insignificant now that DAAs are incorporated into standard of care [88]. ...
Background:
People living with human immunodeficiency virus (PLHIV) have a similar prevalence of psoriasis as the general population, though incidence and severity correlate with HIV viral load. Adequately treating HIV early renders the infection a chronic medical condition and allows PLHIV with a suppressed viral load (PLHIV-s) to live normal lives. Despite this, safety concerns and a lack of high-level data have hindered the use of systemic psoriasis therapies in PLHIV-s.
Objectives:
We aim to provide a structured framework that supports healthcare professionals and patients discussing the risks and benefits of systemic psoriasis therapy in PLHIV-s. Our goal was to address the primary question, are responses to systemic therapies for the treatment of psoriasis in PLHIV-s similar to those in the non-HIV population?
Methods:
We implemented an inference-based approach relying on indirect evidence when direct clinical trial data were absent. In this instance, we reviewed indirect evidence supporting inferences on the status of immune function in PLHIV. Recommendations on systemic treatment for psoriasis in PLHIV were derived using an inferential heuristic.
Results:
We identified seven indirect indicators of immune function informed by largely independent bodies of evidence: (1) functional assays, (2) vaccine response, (3) life expectancy, (4) psoriasis manifestations, (5) rate of infections, (6) rate of malignancies, and (7) organ transplant outcomes.
Conclusions:
Drug-related benefits and risks when treating a patient with systemic psoriasis therapies are similar for non-HIV patients and PLHIV with a suppressed viral load and normalized CD4 counts. Prior to initiating psoriasis treatment in PLHIV, HIV replication should be addressed by an HIV specialist. Exercise additional caution for patients with a suppressed viral load and discordant CD4 responses on antiretroviral therapy.
... Indeed, PI-containing regimens are associated with higher rates of rejection, graft loss and mortality than PIsparing ARV regimens.(35,36) Conversely, non-nucleoside reverse transcriptase inhibitors (NNRTIs) may induce these enzymes, and reduce CNI levels.(37) ...
Background
The incidence of end-stage organ disease in people living with HIV (PLWH) is increasing, as people live longer due to potent, tolerable antiretroviral therapy. Consequently, the number of PLWH who would benefit from solid organ transplant (SOT) is rising. Solid organ transplantation experience in PLWH in Australia remains limited. The aim of this study was to retrospectively review the outcomes for SOT in PLWH in Victoria, Australia.
Methods
A retrospective cohort study of PLWH undergoing SOT over a 15-year period was performed. Adult PLWH over 18 years of age were eligible and identified from the Victorian HIV Service database. Descriptive statistics were used to summarise baseline demographics and clinical data, and outcomes following SOT.
Results
Nine virologically-suppressed PLWH underwent SOT from HIV-negative donors; 5 kidneys, 2 livers, and 2 bilateral sequential lung transplants. All patients were male, with a median age of 57.3 years (IQR 54.3–60.1), CD4 count of 485 (IQR 342–835) at transplantation, and comorbidities were common at baseline. After a median follow up of 3.9 years (IQR 2.7–7.6), 8 (89%) patents were alive, 7 (78%) had functioning grafts, though 5 (56%) experienced organ rejection. Infections were common. Two patients required modification to their antiretroviral therapy due to significant drug–drug interactions, prior to transplant, while 5 (56%) had modifications post-SOT. No patients experienced HIV virologic failure.
Conclusion
PLWH with end-stage organ disease experience good clinical and functional outcomes, and should be considered for SOT where indicated. However, multidisciplinary planning and care is essential to optomise care in this patient group.
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... Kidney transplant outcomes in the HAART era are similar between HIV-positive and negative patients with the 3-year patient and graft survival of 90%. 4,5 Similar outcomes have been reported in liver transplantation with equivalent 1-, 3-, and 5-year patient and graft survival rates between HIV-positive and negative liver transplant recipients. 6 Orthotopic heart transplantation (OHT) is rarely performed in HIVpositive patients despite the fact that HIV-associated cardiomyopathy is a major long-term complication of HIV infection. ...
Background:
Human immunodeficiency virus (HIV) infection affects nearly 38 million people worldwide. Patients living with HIV (PLHIV) on modern highly active antiretroviral therapy face significant morbidity and mortality related to the progression of chronic diseases, which lead to an increase in the burden of end-stage organ disease and organ failure. PLHIV present a two fold increased risk of heart failure as compared with the general population, with a prevalence of clinical heart failure of 6.5 %. Orthotopic heart transplantation (OHT) is rarely performed in HIV-positive patients despite the fact that HIV-associated cardiomyopathy is a major long-term complication of HIV infection.
Material and methods:
We present a case of PLHIV presenting with decompensated heart failure, requiring initial therapy with left ventricular assist device, followed by heart transplantation, accompanied by an update on current concepts, and experience in the field.
Discussion and conclusion:
HIV-associated cardiomyopathy is a major long-term complication of HIV infection. LVAD support or OHT should also be encouraged among HIV-positive patients as current data indicates that AHFT is safe in carefully selected HIV-positive patients and outcomes are similar to those of HIV-negative patients.
... Contemporary cohorts of HIV-infected transplant recipients have demonstrated excellent patient and graft survival [1][2][3][4][5][6][7]. Similarly, for patients with hepatitis C virus (HCV) infection, kidney transplantation offers a survival benefit and can be more cost-effective than remaining on the waitlist [8][9][10]. ...
... In the pre-DAA era, transplantation in patients coinfected with HIV and HCV was associated with reduced graft survival and higher rates of serious infection [25]. However, recent small case series showed improved outcomes, including fewer infectious complications, in coinfected patients treated with DAA after transplant [3,4,6]. ...
... Management of DDI in patients coinfected with HIV and HCV is paramount, even more so in the setting of organ transplantation [3-5, 7, 13]. Fewer DDI are probably one of the main factors responsible for improved outcomes with InSTI compared to PI after organ transplantation in patients with HIV [4]. Coadministration of GLE/PIB with systemic tacrolimus (1 mg single dose) has been shown to increase tacrolimus C max and area under the curve (AUC) by 1.5-fold and 1.45-fold, respectively. ...
Despite significant advances in transplantation of HIV-infected individuals, little is known about HIV coinfected patients with hepatitis C virus (HCV) genotypes other than genotype 1, especially when receiving HCV-infected organs with a different genotype. We describe the first case of kidney transplantation in a man coinfected with hepatitis C and HIV in our state. To our knowledge, this is also the first report of an HIV/HCV/HBV tri-infected patient with non-1 (2a) HCV genotype who received an HCV-infected kidney graft with the discordant genotype (1a), to which he converted after transplant. Our case study highlights the following: (1) transplant centers need to monitor wait times for an HCV-infected organ and regularly assess the risk of delaying HCV antiviral treatment for HCV-infected transplant candidates in anticipation of the transplant from an HCV-infected donor; (2) closer monitoring of tacrolimus levels during the early phases of anti-HCV protease inhibitor introduction and discontinuation may be indicated; (3) donor genotype transmission can occur; (4) HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation.
... In a study by Rosa et al., patients receiving PI-containing regimens had lower PS at 1 and 3 years than patients receiving PI-sparing regimens-85% vs. 100% (p = 0.06) and 82% vs. 100% (p = 0.03), respectively [40]. ...
Background:
Kidney transplantation is now a viable alternative to dialysis in HIV-positive patients who achieve good immunovirological control with the currently available antiretroviral therapy regimens. This systematic review and meta-analysis investigate the published evidence of outcome and risk of kidney transplantation in HIV-positive patients following the PRISMA guidelines.
Methods:
Searches of PubMed, the Cochrane Library and EMBASE identified 27 cohort studies and 1670 case series evaluating the survival of HIV-positive kidney transplant patients published between July 2003 and May 2018. The regimens for induction, maintenance therapy and highly active antiretroviral therapy, acute rejection, patient and graft survival, CD4 count and infectious complications were recorded. We evaluated the patient survival and graft survival at 1 and 3 years respectively, acute rejection rate and also other infectious complications by using a random-effects analysis.
Results:
At 1 year, patient survival was 0.97 (95% CI 0.95; 0.98), graft survival was 0.91 (95% CI 0.88; 0.94), acute rejection was 0.33 (95% CI 0.28; 0.38), and infectious complications was 0.41 (95% CI 0.34; 0.50), and at 3 years, patient survival was 0.94 (95% CI 0.90; 0.97) and graft survival was 0.81 (95% CI 0.74; 0.87).
Conclusions:
With careful selection and evaluation, kidney transplantation can be performed with good outcomes in HIV-positive patients.
... 4,8 Once considered a contraindication for solid organ transplantation, the feasibility of kidney transplantation in HIVþ individuals is now well-established. 4,[8][9][10][11][12][13][14][15][16][17][18][19] In the absence of hepatitis C virus (HCV) coinfection, transplant outcomes and patient/graft survival rates resemble those of HIVÀ controls. 11,14 Even more, favorable outcomes in HIVþ/HCVþ kidney recipients have been recently reported in the direct-acting antiviral era for HCV therapy. ...
Introduction:
HIV-positive (HIV+) kidney transplant recipients exhibit a 2- to 3-fold increased risk of allograft rejection. Dysregulated immune activation in HIV infection persists despite successful antiretroviral therapy and is associated with non-AIDS morbidity, including renal disease. We hypothesized that the pathological levels of inflammation and immune activation associated with chronic HIV infection could have clinical utility in the prediction of rejection in HIV+ kidney recipients.
Methods:
Prospective cohort study of 22 HIV-negative (HIV-; donor) to HIV+ (recipient) kidney transplant recipients who underwent biomarker assessment pretransplant and were subsequently followed for development of acute rejection. Plasma levels of markers of inflammation (soluble tumor necrosis factor receptor 1 [sTNF-R1] and C-reactive protein [CRP]) and microbial translocation (soluble CD14 and lipopolysaccharide) were measured by enzyme-linked immunosorbent assay or chromogenic endpoint assay. Levels of activated (CD38+HLADR+) CD4+ and CD8+ T cells, and T regulatory cells (CD4+CD25highFoxP3+) were measured by flow cytometry.
Results:
Among the biomarkers evaluated, only the pretransplant levels of sTNF-R1, CRP, and frequencies of CD38+HLADR+ CD8 T cells, were found to be at significantly higher levels among patients who experienced biopsy-proven acute rejection. Confirming our hypothesis, patients with high pretransplant levels of sTNF-R1 or activated CD8+ T cells had a significantly increased 200-day cumulative incidence of biopsy-proven acute rejection (0 vs. 38% for both; P = 0.01). Similarly, pretransplant CRP levels higher than 5 μg/ml were associated with increased risk of acute rejection within the first 6 months post-transplant (0 vs. 43%; P = 0.01).
Conclusion:
Biomarker-based identification of HIV+ recipients at increased risk for rejection might facilitate individualized induction immunosuppression regimens in this vulnerable patient population.
... 2-1.8-fold) and mortality (1.8-12.1-fold) among kidney transplant patients[67,68]. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) display varying CYP effects; efavirenz and nevirapine are potent inducers and lower CNI/MTOR inhibitor levels, while etravirine and rilpivirine exhibit little effect. ...
Purpose of Review
End-stage organ disease prevalence is increasing among HIV-infected (HIV+) individuals. Trial and registry data confirm that solid organ transplantation (SOT) is efficacious in this population. Optimizing access to transplant and decreasing complications represent active frontiers.
Recent Findings
HIV+ recipients historically experienced 2–4-fold higher rejection. Integrase strand transferase inhibitors (INSTIs) minimize drug interactions and may reduce rejection along with lymphodepleting induction immunosuppression. Hepatitis C virus (HCV) coinfection has been associated with inferior outcomes, yet direct-acting antivirals (DAAs) may mitigate this. Experience in South Africa and the US HIV Organ Policy Equity (HOPE) Act support HIV+ donor to HIV+ recipient (HIV D+/R+) transplantation.
Summary
SOT is the optimal treatment for end-stage organ disease in HIV+ individuals. Recent advances include use of INSTIs and DAAs in transplant recipients; however, strategies to improve access to transplant are needed. HIV D+/R+ transplantation is under investigation and may improve access and provide insights for HIV cure and pathogenesis research.
... One suggested first line regimen is the combination of abacavir (or tenofovir as an alternative), lamivudine/ emtricitabine, and raltegravir (48). Another study showed PI sparing ART regimens is superior than PI-containing in HIV-positive kidney transplant recipients (49). In general, the ideal ART regimen must maintain viral suppression and increased CD4 count, while preserving renal graft function and avoiding pharmacokinetic interactions with immunosuppressive medications. ...
Human immunodeficiency virus (HIV) infection has long been a contraindication to kidney transplantation due to transplant immunosuppression, HIV-associated renal dysfunction, and nephrotoxicity associated with antiretroviral therapy (ART). However, advances in antiretroviral therapies and transplant immunosuppression regimens have allowed patients to successfully undergo kidney transplantation. Emerging data has shown that kidney transplantation may be a viable option for appropriately selected HIV patients with end-stage renal disease (ESRD). In this review, we discuss the indications, immunosuppression protocols, and outcomes of kidney transplantation in HIV patients.
... Despite robust evidence of drug-drug interactions between PIs and calcineurin inhibitors, many patients are still regularly referred for transplant evaluation while maintained on PI-based regimens, even in the absence of antiretroviral resistance. (3,4) We understand reluctance to alter patient regimens given provider concerns for loss of control of HIV infection and patient concerns about new and/or additional side effects, but we believe our data further elucidate the association between PIs and adverse outcomes among HIV+ kidney transplant recipients. Moreover, we feel strongly that these data support the routine transition of HIV+ transplant candidates to non-PI regimen whenever medically feasible, and are hopeful these data will assist with the development of evidence-based protocols for HIV+ kidney transplantation. ...
We thank Dr. Sullivan for his thoughtful commentary on our recent analysis of protease inhibitors (PI) and kidney transplant outcomes among HIV-infected kidney transplant recipients.(1, 2) He suggests that post-transplant PI use may be a marker of more advanced HIV infection, driven by genotypic evidence of HIV resistance to multiple classes of antiretroviral therapies. Thus, with a complicated HIV treatment history, the increased association of PIs with post-transplant mortality may actually be capturing the risk of death associated with antiretroviral resistance, rather than an impact of PIs themselves on outcomes.
