INTRODUCTION — Kidney transplantation is accepted as the ideal therapy for end-stage kidney disease (ESKD). Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for transplantation because of the concern that immunosuppression would accelerate HIV disease progression, resulting in increased mortality and a "waste" of organs .
Since potent antiretroviral therapy (ART) became widely available in 1996 , the prognosis of patients with HIV infection has dramatically improved. There have been significant decreases in morbidity and mortality, and, for many individuals with well-controlled viral replication, HIV is now a chronic, manageable disease [3,4].
Improvements in the long-term prognosis of those with HIV infection and studies demonstrating good outcomes with kidney transplantation have prompted many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. A review of the issues surrounding kidney transplantation inpatients with HIV is presented here.
An overview of kidney disease in patients with HIV and a discussion of HIV-associated nephropathy (HIVAN) are presented elsewhere:
EPIDEMIOLOGY AND OUTCOMES
Patient and graft survival
Pre-ART era — Prior to the introduction of potent antiretroviral therapy (ART), kidney transplantation was associated with poor patient and allograft outcomes in patients with HIV . In many patients, HIV infection was only diagnosed retrospectively or acquired peritransplant by transfusion or transplantation with infected organs. The improvement in patient survival with ART called into question the previous policy of systematically denying transplantation to individuals with HIV [1,6].
Transplantation in the ART era — Several studies have demonstrated comparable short- and intermediate-term patient and graft outcomes between HIV-infected and HIV-uninfected patients who underwent kidney transplantation after the introduction of potent antiretroviral therapy (ART) [7-20]. As examples:
●A prospective, nonrandomized trial examined outcomes of kidney transplantation in 150 recipients with HIV who had CD4 counts of ≥200 cells/microL and undetectable HIV RNA levels between November 2003 and June 2009 . Patient survival at one and three years was 95 and 88 percent, respectively; allograft survival was 90 and 74 percent, respectively. These survival rates fell in between those for recipients older than 65 years of age and those for all kidney transplant recipients, as reported by the Scientific Registry of Transplant Recipients (SRTR). At a median follow-up of four years, patient and allograft survival remained stable at 89 and 69 percent .
●Longer-term outcomes, however, remain unclear. In a retrospective, single-center study that compared long-term outcomes between 119 recipients with HIV and 655 propensity-matched recipients without HIV, patient survival at 15 years was lower among those with HIV (54 versus 80 percent, respectively), but graft survival was comparable between the two groups (75 versus 57 percent, respectively) . Long-term graft survival was lower among patients who had at least one episode of acute rejection compared with those without rejection (53 versus 92 percent, respectively). These findings have not yet been replicated in a national cohort, and there remains a robust survival benefit associated with kidney transplantation in persons living with HIV. (See 'Risk of rejection' below.)
Outcomes appear to be poorer among transplant recipients who are coinfected with HIV and hepatitis C virus (HCV) [6-8]. As an example, in a retrospective analysis of United Network for Organ Sharing (UNOS) data that compared outcomes for 492 HIV-infected recipients and 147 HIV/HCV-coinfected recipients, there was no significant difference in patient or allograft survival between HIV-monoinfected recipients and an uninfected reference group . However, an increased risk of mortality (hazard ratio [HR] 2.26, 95% CI 1.45-3.52) and graft loss (HR 2.59, 95% CI 1.60-4.19) was observed in the HIV/HCV-coinfected cohort. Outcomes of HCV/HIV-coinfected recipients have improved with the advent of direct-acting antiviral (DAA) therapy .
The impact of new therapies for HCV on posttransplantation outcomes for coinfected patients has yet to be determined, although limited data suggest a beneficial effect of HCV treatment on outcomes . A discussion of kidney transplant in HCV-infected patients is found elsewhere. (See "Hepatitis C infection in kidney transplant candidates and recipients".)
In patients with HIV and end-stage kidney disease (ESKD), kidney transplantation has been associated with a survival benefit over chronic dialysis. In a study of 1431 kidney transplant candidates with HIV, the risk of mortality at five years was significantly lower among those who underwent kidney transplantation compared with those who remained on dialysis (adjust relative risk [aRR] 0.21, 95% CI 0.10-0.42), and a survival benefit was achieved at 194 days posttransplant . Among patients coinfected with HCV, kidney transplant was also associated with a lower risk of death compared with dialysis, although the survival benefit was not achieved until 392 days posttransplant. While kidney transplantation has become more common among patients with HIV, the burden of ESKD remains high among individuals with HIV despite ART, and they are less likely to achieve transplantation than their uninfected counterparts .
Risk of rejection — Kidney transplant recipients with HIV have a high frequency of rejection. In a large, multicenter trial, one- and three-year rejection rates were 31 and 41 percent, respectively, compared with an expected one-year rejection rate of 12 percent, as reported by SRTR for all kidney transplant recipients . At European transplant centers, where most patients are induced with interleukin (IL)-2 receptor antibodies, one-year, acute rejection rates among recipients with HIV have ranged from 15 to 44 percent [24-26].
The higher rate of rejection in recipients with HIV is likely multifactorial. Drug-drug interactions between calcineurin inhibitors (CNIs) and protease inhibitors (PIs) can lead to subtherapeutic exposure to immunosuppressive agents. Patients on a CNI and PI require nonstandard dosing schedules (ie, every other or every third day), which can make patient adherence difficult. Furthermore, concomitant administration of a PI and CNI results in a 40 percent lower area under the curve (AUC) for CNI exposure at the same CNI target level, leading clinicians to systematically underdose patients taking both medications. In light of these challenges, many transplant professionals seek to transition patients off PI-based regimens whenever possible in favor of integrase inhibitor-based regimens, which avoid these drug-drug interactions and permit standard immunosuppression dosing (see "Overview of antiretroviral agents used to treat HIV", section on 'Integrase strand transfer inhibitors (INSTIs)'). Additionally, given concerns about overimmunosuppression, many patients with HIV are given IL-2 receptor antibody induction rather than lymphocyte-depleting agents, and this may also increase their acute rejection risk. (See "Kidney transplantation in adults: Induction immunosuppressive therapy", section on 'Recipients with HIV'.)
Malignancy — Kidney transplant patients are at increased risk for the development of malignancy . (See "Malignancy after solid organ transplantation" and "Epidemiology and risk factors for skin cancer in solid organ transplant recipients".)
Limited evidence suggests that HIV infection does not increase the risk for posttransplant malignancy. In one large, multicenter trial of 150 transplant recipients with HIV, only 13 (8.7 percent) developed cancer . The most common malignancy was skin cancer, and in 3.5 years of follow-up, there were three cancer-related deaths.
Infection risk — Nonopportunistic infections are common in kidney transplant recipients with HIV and mirror the trend seen in HIV-negative kidney transplant recipients . In one study, one-half of recipients were hospitalized within the first six months posttransplant for infection . HCV coinfection and induction with antithymocyte globulin (ATG) increased the risk of posttransplant infection. The most common etiologies were bacterial infections of the blood, urinary system, or respiratory tract. Another study using SRTR data linked to Medicare claims found no difference in posttransplant infection rates between different types of induction .
ELIGIBILITY CRITERIA — Kidney transplantation is now accepted as "standard of care" for HIV-positive patients with end-stage kidney disease (ESKD); however, the majority of these transplants continue to be performed at large, academic medical centers with robust transplant infectious disease support.
Kidney transplant candidates with HIV must meet center-specific, general transplant candidate selection criteria in addition to HIV-specific criteria (see "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient"). There are no established HIV-specific selection criteria for recipients, but most centers follow the patient selection criteria set forth in a National Institutes of Health (NIH) multicenter trial , which specified that patients must have an undetectable viral load and a CD4 count of >200 cells/microL on a stable antiretroviral therapy (ART) regimen for at least six months. These criteria do not exclude patients who have an isolated, low-level, detectable HIV RNA below 200 copies/mL (referred to as a viral blip). (See "Patient monitoring during HIV antiretroviral therapy", section on 'Approach to viral blips and persistent low-level viremia'.)
Opportunistic infections (OIs) are no longer a cause for exclusion, but patients with a history of Kaposi sarcoma, central nervous system (CNS) lymphoma, or progressive multifocal leukoencephalopathy should be considered on a case-by-case basis and may not be considered candidates at many centers. Patients who are coinfected with hepatitis C virus (HCV) or hepatitis B virus (HBV) require hepatology evaluation and an assessment of liver fibrosis. (See "Hepatitis C infection in kidney transplant candidates and recipients", section on 'HCV evaluation of transplant candidates' and "Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients", section on 'Pretransplantation assessment of HBV status'.)
PRETRANSPLANT EVALUATION — In general, the pretransplant evaluation of individuals with HIV is similar to that of individuals without HIV. This includes screening for latent tuberculosis by tuberculin skin test (TST) or interferon-gamma release assay and updating vaccinations. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient" and "Immunizations in solid organ transplant candidates and recipients".)
In addition, the pretransplant evaluation includes obtaining an HIV viral load, CD4 count, and detailed HIV medication history. Candidates with HIV should be evaluated for potential drug interactions between the patient's antiretroviral therapy (ART) and planned immunosuppressive agents . If possible, the ART regimen should be switched to a regimen that does not include a protease inhibitor or cobicistat because of their profound effects of the CYP3A4 system. In general, integrase inhibitor-based regimens that include dolutegravir or bictegravir are preferred. This is discussed in more detail elsewhere in this topic. (See 'Management of antiretroviral therapy' below.)
PHARMACOLOGIC MANAGEMENT — Pharmacologic management in kidney transplant recipients with HIV involves the administration of immunosuppression in combination with potent antiretroviral therapy (ART).
Management of immunosuppression
Induction therapy — Options for induction immunosuppression therapy in kidney transplant recipients with HIV include rabbit antithymocyte globulin (rATG)-Thymoglobulin, interleukin (IL)-2 receptor antibodies, glucocorticoids, and alemtuzumab, with the majority of transplant centers in the United States using either rATG-Thymoglobulin or IL-2 receptor antibodies. The use of induction immunosuppression in kidney transplant recipients with HIV is discussed in more detail elsewhere. (See "Kidney transplantation in adults: Induction immunosuppressive therapy", section on 'Recipients with HIV'.)
Maintenance therapy — In kidney transplant recipients with HIV, we, and most centers transplanting recipients with HIV, administer triple immunosuppression therapy as an initial maintenance regimen. This typically includes all of the following:
●A calcineurin inhibitor (CNI; eg, tacrolimus)
●An antimetabolite (eg, mycophenolate)
Such a regimen is similar to that used in HIV-uninfected transplant recipients. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Although cyclosporine may have some antiviral effects in vitro [32,33], tacrolimus is the preferred CNI in transplant recipients with HIV. In an observational cohort study of 78 kidney transplant patients with HIV induced with IL-2 receptor antibodies, use of tacrolimus as part of maintenance immunosuppression was associated with a lower incidence of acute rejection compared with cyclosporine (21 versus 58 percent, respectively) . Posttransplant tacrolimus target levels may vary by transplant center and depend upon the induction agent used, degree of allosensitization, and time posttransplant. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy", section on 'Target levels for calcineurin inhibitors'.)
Although the use of glucocorticoid-sparing regimens in kidney transplant recipients with HIV has also been reported [34,35], we do not routinely discontinue glucocorticoids in our patients. In addition, we do not routinely use mammalian (mechanistic) target of rapamycin (mTOR) inhibitors (eg, sirolimus) as maintenance immunosuppression in transplant patients with HIV. Although one secondary analysis of data from a large, nonrandomized trial of kidney transplant recipients with HIV found that maintenance immunosuppression that included sirolimus, but not tacrolimus, was associated with lower posttransplant proviral DNA levels , other studies in transplant recipients with HIV have shown that use of sirolimus was associated with a significantly higher risk of acute rejection (adjusted hazard ratio [aHR] 2.15, 95% CI 1.20-3.87) .
Management of antiretroviral therapy — Patients being considered for transplant must be virologically suppressed on a stable ART regimen. The main considerations about ART in a potential kidney transplant recipient are toxicities and drug interactions. Thus, the patient's regimen may need to be modified. Consultation with an HIV medicine expert is recommended before switching regimens.
Potential modifications include:
●Nucleos(t)ide (NRTI) combination – For patients receiving a tenofovir-containing regimen, the provider must decide which formulation of tenofovir to use. There are two formulations of tenofovir, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). There is more clinical experience with TDF; however, TAF has less kidney and bone toxicity.
•For patients with an estimated glomerular filtration rate (eGFR) >15 mL/min/1.73 m2, we prefer TAF plus emtricitabine (FTC). For those with an eGFR >30 mL/min/1.73 m2, the coformulated tablet of TAF-FTC can be used. For those with an eGFR between 15 and 30 mL/min/1.73 m2, TAF and FTC (or the closely related agent lamivudine [3TC]) must be given separately and the dose of FTC or 3TC adjusted according to kidney function.
•For patients with an eGFR of <15 mL/min/1.73 m2, including those on dialysis, we typically administer TDF plus either FTC or 3TC; all of these agents must be adjusted according to kidney function. After transplantation, and when the eGFR is >15 mL/min/1.73 m2, the nucleoside regimen can be switched to TAF-FTC as described above. However, in the pretransplant setting, TDF is still used in patients with an eGFR <15 mL/min/1.73 m2 and in those on dialysis, given the paucity of data using TAF in this setting.
If TDF or TAF cannot be used (eg, adverse reaction or concerns about toxicities such as osteoporosis with TDF), an alternative option is abacavir (no renal adjustment necessary) and dose-adjusted FTC or 3TC; however, the patient must first be tested for HLA-B5701 as abacavir is contraindicated in patients who are HLA-B5701 positive.
●Choice of third agent – Some patients will have virologic suppression on an initial regimen that includes an NRTI combination with a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) as the third agent. Both PIs and NNRTIs are associated with an increased risk of drug interactions (see 'Drug interactions' below). In addition, among kidney transplant recipients with HIV, the use of PI-based regimens has been associated with a higher risk of allograft loss (particularly in the first year after transplantation) and death compared with the use of non-PI-based regimens . Thus, in kidney transplant candidates with HIV who are on a PI, we generally convert to an integrase strand transfer inhibitor (INSTI)-based regimen prior to transplantation.
Patients who are virologically suppressed on their initial regimen can usually continue their NRTI combination and have the third agent switched to an INSTI since preexisting integrase resistance is very rare . INSTIs are generally preferred as the third agent because they are less likely to result in drug interactions.
For most patients, we prefer dolutegravir as the INSTI; however, raltegravir is an acceptable alternative if drug interactions or cost preclude the use of dolutegravir. We typically avoid elvitegravir because it is only available in a coformulated tablet that is not suitable for patients with end-stage kidney disease (ESKD). In addition, there is an increased risk of drug interactions with elvitegravir because it requires cobicistat as a boosting agent. Bictegravir is available as a single tablet combination with emtricitabine and TAF and can be used in patients with an eGFR >30 mL/min/1.73 m2 when the kidney function has stabilized after the transplant; however, experience with this agent is limited in the transplant population. Special considerations regarding the use INSTIs in persons of childbearing potential are discussed elsewhere. (See "HIV and women".)
The approach to antiretroviral treatment in patients who have drug-resistant virus can be complicated in the transplant setting since a PI, which puts patients at increased risk for drug interactions, is often used. A more detailed discussion of how to select a regimen for patients with drug-resistant virus is found elsewhere. (See "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)
Drug interactions — PIs require dosing with a boosting agent, like ritonavir or cobicistat. Ritonavir is a potent inhibitor of the cytochrome P450 system, the main metabolic pathway for CNIs [40-42]. Thus, PIs can significantly reduce metabolism and increase the blood levels of CNIs (table 1 and table 2 and table 3) . In addition, the PI atazanavir should be used with caution because the use of proton pump inhibitors, which are frequently used in transplantation, interferes with its absorption.
Cobicistat is another potent CYP3A4 antagonist that, like ritonavir, can be used to boost PIs and the integrase inhibitor elvitegravir. Patients concomitantly receiving CNIs and a PI or cobicistat will require significant dose adjustments in the CNI. For patients on cyclosporine, a typical dose would be 25 mg every 24 to 48 hours, while those on tacrolimus-based regimens may require 0.5 to 1 mg every five to eight days [44,45].
By contrast, NNRTIs are inducers of cytochrome P450 and can lead to low levels of CNIs when the drugs are coadministered; however, the potency of this effect varies among members of the NNRTI class. Patients taking an NNRTI and CNI together usually require a 1.5- to 2-fold increase in CNI dose to achieve target trough levels .
Maraviroc, an entry inhibitor, also interacts with ritonavir and should be used cautiously in patients receiving PIs. However, it is neither an inhibitor nor inducer of CYP3A4, and, therefore, it does not affect CNI levels. There is an ongoing multi-center trial investigating the adjuvant use of maraviroc to mediate the elevated acute rejection risk observed in this patient population; however, a separate single-center report did not demonstrate a benefit on acute rejection rates .
Raltegravir, dolutegravir, and bictegravir have a low potential for interactions with other antiretrovirals or other drugs used for the management of transplants and are preferentially used in transplant recipients. Elvitegravir, an integrase inhibitor, is always used in combination with cobicistat, and the expected interactions should be similar to any regimen that includes ritonavir.
MONITORING AFTER TRANSPLANTATION
Kidney allograft function — Kidney transplant patients with HIV should receive the same routine posttransplant monitoring as recipients without HIV. From a laboratory perspective, this will involve serial chemistry panels to monitor kidney function and electrolytes; complete blood count to assess leukocytes, hemoglobin, and platelet counts; and measurement of calcineurin inhibitor (CNI) trough levels. However, in patients taking antiretroviral therapy (ART) regimens that do not permit standard CNI dosing, it is reasonable to obtain these laboratory tests more frequently than the usual standard of care. (See "Kidney transplantation in adults: Overview of care of the adult kidney transplant recipient", section on 'Routine follow-up and laboratory monitoring'.)
HIV viral control — Regular monitoring of the HIV viral load and CD4 count is recommended after kidney transplantation at one month and then every three months posttransplant; this is particularly important if the ART was modified in the period after the transplantation. More detailed discussions of patient monitoring and the evaluation of a patient with a detectable viral load on therapy are presented elsewhere. (See "Evaluation of the treatment-experienced patient failing HIV therapy" and "Patient monitoring during HIV antiretroviral therapy".)
PROPHYLAXIS AFTER TRANSPLANTATION — Like other solid organ recipients, kidney transplant recipients with HIV require prophylaxis against the most common posttransplant opportunistic infections (OIs), namely Pneumocystis pneumonia, cytomegalovirus (CMV), and fungal infections. Antimicrobial prophylaxis is also recommended for all patients with latent tuberculosis who were not treated prior to transplant. Prophylaxis against toxoplasmosis is provided by the use of trimethoprim-sulfamethoxazole (TMP-SMX). This agent also provides prophylaxis against urinary tract infections.
The optimal duration of TMP-SMX prophylaxis in transplant recipients with HIV varies by institution. Some centers continue lifelong TMP-SMX based upon the protocols used in the National Institutes of Health (NIH) trial , whereas others administer TMP-SMX for a shorter duration, depending in part upon the CD4 count [48-51].
For patients who have a sulfa allergy, options include atovaquone or dapsone. Patients receiving dapsone should be assessed for glucose-6-phosphate dehydrogenase (G6PD) deficiency. In addition, dapsone is a sulfone, and, although it is usually tolerated by persons who have adverse reactions to TMP-SMX, it may be prudent to avoid dapsone in patients who have had serious reactions to TMP-SMX (eg, Stevens-Johnson syndrome/toxic epidermal necrolysis, rash with fever and systemic symptoms, serum sickness, or hemolytic anemia). (See "Sulfonamide allergy in HIV-uninfected patients", section on 'Cross-reactivity'.)
HIV infection of the allograft — HIV may be capable of infecting kidney allografts even in patients with undetectable viral loads and on antiretroviral therapy (ART). This was shown in a French study of 19 patients with HIV who had no evidence of HIV viremia at the time of transplantation . Using in situ hybridization, HIV RNA was demonstrated in 13 patients in either podocytes or tubular cells on protocol biopsies obtained at 3 and 12 months after transplantation. In five patients with infected podocytes, there was histologic evidence of focal and segmental glomerulosclerosis and early-onset, nephrotic-range proteinuria with a decline in kidney function. Patients with tubular infection had a more benign course; only one patient in this group developed end-stage kidney disease (ESKD). No association was seen with viral tropism (CXCR4 versus CCR5) or apolipoprotein L1 (APOL1) genotype. A quantitative polymerase chain reaction (PCR) assay for HIV RNA and DNA in the urine has been developed to identify patients with infected allografts, but this remains experimental. This phenomenon has not been observed in other, larger studies [17,53,54].
Opportunistic infections — Infections are more likely related to the posttransplant immunosuppressive state, rather than to the HIV infection, since all transplant programs require full control of viral replication and a CD4 count of >200 cells/microL prior to transplantation for kidney transplants. (See 'Eligibility criteria' above.)
Delayed graft function — Delayed graft function (DGF) is defined as the requirement for dialysis in the first week after transplant and is a risk factor for graft loss in both recipients with and without HIV . An analysis of the United Network for Organ Sharing (UNOS) database confirmed the high rates of DGF in recipients with HIV (42.5 percent) as well as its negative impact on allograft survival (hazard ratio [HR] 1.86, 95% CI 1.27-2.73) .
Retransplantation — Patients whose first allograft fails can be considered for retransplantation; second kidney transplants now comprise 13.1 percent of the general waiting list . One study  examined outcomes for 22 patients with HIV who were retransplanted, compared with 4127 HIV-negative matched controls. Unfortunately, in this analysis, patients with HIV who had a second transplant had a 3.1-fold higher risk of death and a 1.96-fold increased risk of allograft loss, questioning the utility of the practice.
Donors with HIV — The National Organ Transplantation Act, passed in 1984, specifically forbid organ donation by persons with HIV. However, as the transplant waitlist has grown, outstripping the available supply of organs, there has been renewed interest in use of donors with HIV infection.
The most extensive experience with the use of HIV-positive-to-HIV-positive transplants comes from South Africa [53,54,60]. In this case series, 51 patients with HIV underwent transplantation with kidneys from deceased donors who tested positive for HIV using a fourth-generation enzyme-linked immunosorbent assay (ELISA) . To be eligible, transplant recipients had to have received antiretroviral therapy (ART) for at least three months, have a CD4 T cell count of ≥200 cells/microL, and have an undetectable HIV RNA level. Potential recipients were excluded who had any history of previous opportunistic infections (OIs), except treated pulmonary tuberculosis.
The deceased donors had received either no or only first-line ART and had undetectable HIV viral loads. Potential donors were excluded if they had severe sepsis, active tuberculosis, stage 4 HIV disease (ie, acquired immunodeficiency syndrome [AIDS]), abnormal kidney function, or proteinuria. All had normal kidney biopsies at the time of transplantation.
Patient survival was 87, 87, and 84 percent at one, three, and five years, respectively. Death-censored graft survival was 96, 93, and 79 percent at one, three, and five years, respectively. Acute rejection was 25, 39, and 44 percent at one, three, and five years, respectively. The HIV viral load remained suppressed in all patients. However, low levels of donor HIV were detected in one recipient, raising the possibility of superinfection.
In the United States, Congress passed the HIV Organ Policy Equity (HOPE) Act in 2013, which permits research in the area of HIV-positive-to-HIV-positive transplantation. The first transplantation from a donor with HIV to a recipient with HIV was performed in March of 2016 at Johns Hopkins [61-63], and since then, several deceased, HIV-positive donor kidney transplantations have been performed. In a multicenter pilot study that compared outcomes of 25 recipients of an HIV-positive donor kidney with those of 50 recipients of an HIV-negative donor kidney, one-year patient and graft survival were comparable between the groups . However, there was a trend toward higher rates of acute rejection among recipients of HIV-positive donor kidneys (50 versus 29 percent). In March 2019 Johns Hopkins performed the first living-donor, HIV-positive kidney transplantation under the HOPE Act, but concerns regarding the safety of the practice, given the risk of kidney disease associated with HIV infection, remain.
Selection criteria for donors with HIV were published by the Department of Health and Human Services in November 2015 . While the overall number of HIV-positive donors procured in the United States has not yet approached prior estimates , an unanticipated benefit of the HOPE Act has been the utilization of donors with false-positive HIV testing results [67,68]. Recipients of donors with HIV have the same HIV-specific selection criteria as those receiving HIV-negative transplants. (See 'Eligibility criteria' above.)
Deceased donors with HIV do not have a CD4 count or HIV viral load requirement but must have no evidence of invasive opportunistic complications of HIV infection, and a preimplantation donor kidney biopsy must be performed.
Living donation of organs from individuals with HIV is permitted under the HOPE Act. Potential living donors must meet center-specific, living-donor criteria and, in addition, must have a CD4 count of >500 cells/microL, an HIV viral load <20 copies/mL (the level of detection by most available assays), and no prior history of invasive OIs. All potential donors must undergo a kidney biopsy prior to donation.
There are also eligibility criteria for centers wishing to perform HIV-positive-to-HIV-positive transplants; they must first have demonstrated experience with HIV-negative to HIV-positive transplantation, have infectious disease programmatic support, have established standard operating procedures for the safe handling of organs from individuals with HIV, have a biohazard plan in place to prevent inadvertent disease transmission, have institutional review board approval, and have an approved variance from the United Network for Organ Sharing (UNOS).
One important concern regarding the use of donors infected with HIV for transplantation has been the potential transmission of virus from the donor. Use of deep phenotyping has demonstrated that donor-derived virus can be detected in recipients of HIV-positive organs, but so far the presence of donor viral strains has only been transient and has not impacted recipient HIV viral control [60,69].
Coinfection with HBV or HCV — Due to shared transmission routes, many patients with HIV are coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). For those who are not coinfected with HBV or HCV, routine screening for these viruses pre- and posttransplantation is indicated , as discussed elsewhere. (See "Kidney transplantation in adults: Overview of care of the adult kidney transplant recipient", section on 'Screening' and "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient", section on 'Laboratory and imaging tests'.)
HBV infection — Patients with HIV undergoing kidney transplantation who also have chronic or resolved hepatitis B virus (HBV) should be treated with a tenofovir-containing ART regimen. Tenofovir is considered a first-line agent for the treatment of HBV and can also prevent reactivation in the setting of immunosuppressive therapy. Both tenofovir formulations (tenofovir disoproxil fumarate [TDF] and tenofovir alafenamide [TAF]) are equally effective in maintaining HBV suppression, but TAF may be preferred in the posttransplant setting because it is less nephrotoxic. More detailed discussions of the management of patients with HBV infection, including those who cannot take tenofovir, are discussed elsewhere. (See 'Management of antiretroviral therapy' above and "Treatment of chronic hepatitis B in patients with HIV" and "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
HCV infection — Outcomes for HIV/hepatitis C virus (HCV)-coinfected kidney transplant recipients have been inferior to those with HIV infection alone across several large registry studies [7-9] with an approximately 1.4-fold increased risk of death. (See 'Transplantation in the ART era' above.)
Since the clinical availability of direct-acting antivirals (DAAs) for the treatment of HCV, there has been optimism that clearance of HCV infection will improve outcomes for this population [20,71-75], but this has not been prospectively studied in coinfected HIV/HCV transplant recipients. In one case report of six HIV/HCV-coinfected kidney transplant recipients treated with ledipasvir-sofosbuvir, 100 percent of patients achieved a sustained viral response at 12 weeks after completion of therapy, and HCV treatment was well tolerated . Tacrolimus dosing needed adjustment during and after therapy, but no changes to antiretroviral regimens were required. One small study demonstrated improved patient and allograft survival in HIV/HCV coinfected recipients who were treated posttransplantation with DAAs , but this beneficial effect remains to be demonstrated in larger patient cohorts.
ART should not be interrupted to facilitate HCV treatment but, in some cases, may need to be modified. Treatment of HCV in HIV/HCV-coinfected kidney transplant recipients should be coordinated with a transplant infectious disease clinician.
Detailed discussions of the management of HIV/HCV coinfected patients and the management of HCV-infected patients undergoing transplant are found elsewhere. (See "Treatment of chronic hepatitis C virus infection in the patient with HIV" and "Hepatitis C infection in kidney transplant candidates and recipients".)
FUTURE DIRECTIONS — There is interest in the use of maraviroc, a CC chemokine receptor 5 (CCR5) inhibitor, to improve survival in kidney transplant recipients with HIV. CCR5 is a coreceptor of HIV-1. (See "Overview of antiretroviral agents used to treat HIV", section on 'Entry inhibitors' and "Transplantation immunobiology".)
Approximately 1 percent of White individuals are homozygous carriers of an allele of the gene for CCR5 with a 32-base-pair deletion (CCR5del32), which leads to an inactive receptor . Individuals with CCR5del32 are highly resistant to infection with HIV-1 [78,79]. Other studies have also demonstrated that individuals that are homozygous for this gene have a lower risk of asthma, rheumatoid arthritis, and multiple sclerosis [80-82]. They may also have superior allograft survival after transplantation.
The relationship between kidney allograft survival and CCR5 genotype was evaluated in one study . Among 1227 kidney transplant recipients, 21 were homozygous for CCR5del32, and 248 were heterozygous for CCR5del32. Allograft survival was superior in individuals who were homozygous for CCR5del32 (hazard ratio [HR] 0.367, 95% CI 0.157-0.859). The exact mechanism of this improved survival is unknown. (See "Kidney transplantation in adults: Risk factors for graft failure", section on 'Gene polymorphisms'.)
Given these findings, a clinical trial (NCT02741323) evaluating the effects of maraviroc is in progress.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Solid organ transplantation in individuals with HIV".)
SUMMARY AND RECOMMENDATIONS
●General principles – Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for transplantation because of the concern that immunosuppression would accelerate HIV disease progression, resulting in increased mortality and a "waste" of organs. However, improvements in the long-term prognosis of those with HIV infection and studies demonstrating good outcomes with kidney transplantation have prompted many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. (See 'Introduction' above.)
●Epidemiology and outcomes – Since the introduction of potent antiretroviral therapy (ART), several studies have demonstrated comparable patient and graft outcomes in patients with and without HIV who underwent kidney transplantation. However, outcomes appeared to be poorer among transplant recipients who are coinfected with HIV and hepatitis C virus (HCV) but have improved in the HCV DAA era. In addition, transplant recipients with HIV are at an increased risk of rejection and malignancy post-transplant. (See 'Epidemiology and outcomes' above.)
●Eligibility criteria – Kidney transplantation is now accepted as "standard of care" for patients with HIV and end-stage kidney disease (ESKD); however, the majority of these transplants continue to be performed at large, academic medical centers with robust transplant infectious disease support. Kidney transplant candidates with HIV must meet center-specific, general transplant candidate-selection criteria in addition to HIV-specific criteria. There are no established HIV-specific selection criteria for recipients, but most centers follow the patient-selection criteria set forth in a National Institutes of Health (NIH) multicenter trial, which specified that patients must have a viral load below the limit of detection and a CD4 count of >200 cells/microL on a stable ART regimen for at least six months. History of treated opportunistic infections (OIs) is not a cause for exclusion, but patients with a history of Kaposi sarcoma, central nervous system (CNS) lymphoma, or progressive multifocal leukoencephalopathy should be considered on a case-by-case basis and may not be considered candidates at many centers. Patients who are coinfected with HCV or hepatitis B virus (HBV) require hepatology evaluation and an assessment of liver fibrosis. (See 'Eligibility criteria' above.)
●Pharmacologic management – Pharmacologic management in kidney transplant recipients with HIV involves the administration of immunosuppression in combination with potent ART:
•Options for induction immunosuppression therapy include rabbit antithymocyte globulin (rATG)-Thymoglobulin, interleukin (IL)-2 receptor antibodies, glucocorticoids, and alemtuzumab, with the majority of transplant centers in the United States using either rATG-Thymoglobulin or IL-2 receptor antibodies. (See 'Induction therapy' above.)
•In kidney transplant recipients with HIV, most centers administer triple immunosuppression therapy as an initial maintenance regimen. This typically includes a calcineurin inhibitor (CNI; eg, tacrolimus), an antimetabolite (eg, mycophenolate), and prednisone. Such a regimen is similar to that used in HIV-negative transplant recipients. (See 'Maintenance therapy' above.)
•Patients being considered for transplant must be virologically suppressed on a stable ART regimen. The main considerations about ART in a potential kidney transplant recipient are toxicities and drug interactions. Thus, the patient's regimen may need to be modified. Integrase-inhibitor-based regimens are preferred because of the limited drug interactions. (See 'Management of antiretroviral therapy' above.)
●Monitoring after transplantation – Kidney transplant patients with HIV should receive the same routine, posttransplant monitoring as HIV-negative recipients. From a laboratory perspective, this will involve serial chemistry panels to monitor kidney function and electrolytes; complete blood count to assess leukocytes, hemoglobin, and platelet counts; and measurement of CNI trough levels. In patients taking ART regimens that do not permit standard CNI dosing, it is reasonable to obtain these laboratory tests more frequently than the usual standard of care. Regular monitoring of the HIV viral load and CD4 count is recommended after kidney transplantation at one month and then every three months posttransplant; this is particularly important if the ART was modified in the period after the transplantation. (See 'Monitoring after transplantation' above.)
●Prophylaxis after transplantation – Kidney transplant recipients with HIV require prophylaxis against the most common posttransplant OIs, namely Pneumocystis pneumonia, cytomegalovirus (CMV), and fungal infections. Antimicrobial prophylaxis is also recommended for all patients with latent tuberculosis who were not treated prior to transplantation. (See 'Prophylaxis after transplantation' above.)
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