Human immunodeficiency virus and dialysis

INTRODUCTION — Kidney disease is an important complication of human immunodeficiency virus (HIV) infection, particularly in individuals of African descent [1]. A collapsing form of focal segmental glomerulosclerosis (FSGS) with associated tubular microcysts and interstitial inflammation is the classic form of HIV-related kidney disease, known as HIV-associated nephropathy (HIVAN). HIV infection has also been associated with other forms of kidney disease, in particular, immune complex disease [2]. With prolonged survival and aging of the population, people living with HIV (PWH) are also at increased risk for chronic kidney disease (CKD) due to comorbid conditions, such as diabetes and hypertension.

Some of these kidney diseases can result in end-stage kidney disease (ESKD). Issues relating to HIV and dialysis will be reviewed here. HIV-related disorders of the kidney are discussed separately:

●(See "Overview of kidney disease in patients with HIV".)

●(See "HIV-associated nephropathy (HIVAN)".)

EPIDEMIOLOGY — Compared with the general population, people living with HIV (PWH) are at increased risk for end-stage kidney disease (ESKD). In a population-based cohort study from Denmark, PWH had a fourfold higher risk of ESKD compared with age- and sex-matched controls [3]. Data from the United States Veterans Affairs (VA) health care system have demonstrated that the risk of ESKD is associated with both HIV-related factors (high HIV-RNA, low CD4, and hepatitis C virus coinfection) and traditional kidney disease risk factors (diabetes, hypertension, and cardiovascular disease) [4]. A subsequent study from the VA suggests that ESKD may occur at a younger age in veterans living with HIV versus those not living with HIV, although the difference is small [5].

Both HIV-related factors and traditional kidney disease risk factors were also associated with a combined endpoint of ESKD and advanced chronic kidney disease (CKD) in two large HIV cohort studies, D:A:D and EuroSIDA [6,7]. In a smaller, retrospective cohort study from Germany, injection drug use and being Black were the only independent risk factors for ESKD in PWH [8]. Over the 20-year study period, these authors observed a decline in the prevalence of ESKD among Black PWH and an increase in the prevalence of ESKD among White PWH, although the racial disparity in ESKD risk remained significant.

Data from the VA health care system and from the Johns Hopkins HIV cohort have also demonstrated a striking disparity in the risk of ESKD among Black PWH, who may have as much as a 30-fold increase in the risk of ESKD compared with White PWH [9-11]. In the VA cohort, the risk of ESKD among Black PWH was similar to that observed among patients with diabetes [9]. Genetic variability in the apolipoprotein L1 (APOL1) gene on chromosome 22 appears to account for a significant proportion of the racial disparity in ESKD risk [12], including the risk of HIV-associated nephropathy (HIVAN) and other forms of focal segmental glomerulosclerosis (FSGS) [13-15]. (See "HIV-associated nephropathy (HIVAN)" and "Focal segmental glomerulosclerosis: Genetic causes", section on 'FSGS in Black patients'.)

Prevalence of human immunodeficiency virus infection in the dialysis population — The prevalence of HIV infection in patients on chronic dialysis has not been well described, but available data suggest that it varies based on the prevalence of HIV infection in the local community.

Nationally representative data on the United States ESKD population are collected by the United States Renal Data System (USRDS). Unfortunately, the Health Care Financing Administration (HCFA) 2728 form, which is used to collect data for the USRDS, no longer collects data on HIV status, unless ESKD is attributed to HIVAN (documented as "AIDS nephropathy" on the 2728 form). As a result, the USRDS no longer provides nationally representative data on the prevalence of HIV infection in the United States dialysis population.

A 2017 analysis of administrative and clinical data from a large United States dialysis provider identified 7211 prevalent PWH among a total dialysis population of 417,756 (1.7 percent) [16]. PWH on chronic dialysis were more likely to be Black and less likely to have ESKD attributed to diabetic kidney disease compared with patients without HIV. There were no clinically significant differences in dialysis modality, although peritoneal dialysis was less common in patients coinfected with HIV and hepatitis C virus.

Although the widespread dissemination of antiretroviral therapy (ART) substantially reduced the incidence of ESKD attributed to HIVAN [17], the true frequency of HIVAN in the ESKD population is difficult to determine, as definitive diagnosis requires kidney biopsy. (See "HIV-associated nephropathy (HIVAN)".)

HUMAN IMMUNODEFICIENCY VIRUS TESTING — We recommend voluntary, confidential HIV testing of all patients on chronic dialysis. This recommendation is consistent with recommendations from the United States Preventive Services Task Force to screen all individuals age 15 to 65 years for HIV infection [18].

Potential clinical benefits of routine screening include:

●Improved patient survival with the use of antiretroviral therapy (ART), regardless of CD4 cell count (see 'Antiretroviral therapy' below)

●Potential to reverse HIV-associated nephropathy (HIVAN) with the initiation of ART [19,20]

●Implementation of measures to prevent transmission to partners, including initiation of ART in the patient and consideration of preexposure prophylaxis in HIV-negative partners (see "HIV infection: Risk factors and prevention strategies")

False-positive results — Compared with low-risk patient populations without end-stage kidney disease (ESKD), conventional HIV testing by enzyme immunosorbent assay (EIA) with confirmatory Western blot in patients with ESKD has been associated with an increased incidence of false-positive EIA and indeterminate Western blot results [21-25].

False-positive and indeterminate results are thought to result from the presence of cross-reacting antibodies against CD4+ T lymphocytes or against viral antigens [23].

Recommendations for HIV screening and confirmatory testing are discussed in detail elsewhere:

●(See "Screening and diagnostic testing for HIV infection".)

●(See "Techniques and interpretation of HIV-1 RNA quantitation".)

TRANSMISSION IN THE DIALYSIS UNIT — HIV transmission in the dialysis setting, which is rare, can be avoided by strict adherence to standard infection-control procedures [26]. Transmission of the hepatitis B virus poses a much greater risk.

Dialysis isolation — As long as health care workers follow standard dialysis unit precautions, no special isolation of people living with HIV (PWH) on dialysis is necessary. The Centers for Disease Control and Prevention (CDC) does not recommend routine isolation or dedicated machines for PWH undergoing hemodialysis, given the low likelihood of patient-to-patient and/or patient-to-staff transmission [27].

Patient-to-patient transmission — In the United States, patient-to-patient transmission of HIV infection has not been reported in a dialysis unit [28]. However, at least four well-documented outbreaks of patient-to-patient HIV transmission have occurred in hemodialysis units outside of the United States, including Argentina (two centers), Colombia, and Egypt [29-31]. Seroconversion was documented in 9 of 13 patients in the Colombian unit and 24 of 39 patients in the Egyptian center. When compared with HIV-positive local controls, nucleotide sequence analyses in nearly half of these cases were consistent with a common source of exposure.

The most likely causes of transmission were breaches in infection-control protocol; however, no single activity could be implicated. Possibilities included reuse of the dialyzer, blood lines, and needles for different patients; the use of a weak chemical germicide (benzalkonium chloride) to reprocess needles; contamination of the ports connecting the dialysis machine to the blood lines; and the use of a contaminated multidose heparin vial.

Needlestick transmission — The risk of HIV seroconversion after a needlestick injury is estimated to be 3 in 1000 or 0.3 percent. By comparison, the estimated risk of transmission after a similar event is 6 to 30 percent and 2 percent for hepatitis B and C virus, respectively [32]. The larger the blood inoculum, the deeper the percutaneous injury, and the later the stage of HIV infection in the source patient, the greater the risk of HIV transmission [33].

Postexposure prophylaxis with antiretroviral therapy (ART) should be offered to exposed health care workers or care partners of patients on home hemodialysis. (See "Management of health care personnel exposed to HIV".)

Education of all health care workers, staff, trainees, and care partners in standard infection-control procedures and needlestick protocols is essential. Although rare, documented patient-to-patient and patient-to-health care worker HIV transmission in the dialysis environment makes routine HIV screening valuable in detecting outbreaks and assisting in the decision to initiate postexposure prophylaxis. Adherence to dialysis unit precautions should minimize the risk of HIV transmission.

Viral levels in ultrafiltrate — There is a paucity of evidence relating to the presence or absence of HIV in hemodialysis ultrafiltrate. In one study of 10 ART-treated patients, slightly lower levels of virus were detected in blood post-hemodialysis as compared with predialysis levels [34]; however, no viral RNA was detectable in the ultrafiltrate. The authors hypothesized that the absence of HIV in the ultrafiltrate could be explained by viral adherence to the dialysis membrane.

HIV virus that is capable of replication is recoverable from peritoneal dialysis effluent [35-37]. One study found that HIV was recoverable at room temperature for up to seven days in peritoneal dialysis drainage bags and up to 48 hours from dry tubing [37]. No difference in viral recovery was demonstrated between 1.5, 2.5, and 4.25 percent dextrose solutions. Because survival of replication-competent HIV requires an intracellular environment, the presence of peritonitis may increase the duration of HIV viability within peritoneal dialysis effluent.

The clinical significance of replication-competent HIV in the peritoneal dialysis effluent is unknown. Although no case of HIV transmission via peritoneal dialysis effluent has been described, the fluid poses a theoretical biological risk to disposal workers and medical personnel. Dilutions to 1:512 of both 10 percent bleach and 50 percent amikacin (Amukin) are effective in preventing HIV recoverability in vitro [37], while household bleach is too dilute to serve as a disinfectant.

ISSUES RELATED TO DIALYSIS MODALITY — There is no strong evidence to suggest that one dialysis modality is superior, and both hemodialysis and peritoneal dialysis should be considered in people living with HIV (PWH) approaching end-stage kidney disease (ESKD) [38].

There are several issues unique to the specific dialysis modality utilized among PWH. These include:

●Hemodialysis access infections and complications

●Dialyzer reuse

●Peritonitis

Hemodialysis access infections and complications — Early arteriovenous fistula (AVF) creation is recommended in all PWH who are approaching ESKD and who plan to use hemodialysis [39]. When an AVF is not technically feasible, we advocate creation of an arteriovenous graft (AVG) rather than a tunneled, cuffed catheter since the latter confers an even higher infection rate regardless of HIV status.

Retrospective studies, largely from the era prior to effective antiretroviral therapy (ART), reported a significant increase in AVG infections and thrombosis in PWH. However, more recent data suggest that PWH undergoing arteriovenous access creation have similar outcomes to patients without HIV [40].

Dialyzer reuse — The Centers for Disease Control and Prevention (CDC) recommends that the care of PWH on hemodialysis include routine dialysis unit precautions, with optional reuse of the dialyzer by the same patient [27]. (See "Reuse of dialyzers".)

Peritonitis — In PWH who are clinically stable on ART, the choice of dialysis modality should be based on patient preference. All patients on peritoneal dialysis should be instructed in precautions to avoid contamination, and providers should be aware of the potential for infection with atypical organisms in patients with advanced immunosuppression. (See "Microbiology and therapy of peritonitis in peritoneal dialysis".)

While retrospective studies from the pre-ART era demonstrated high rates of peritonitis and infections with unusual organisms, limited data are available from the modern ART era. Two small South African studies including patients on peritoneal dialysis taking ART reported conflicting results; in one study, HIV was associated with a higher risk of peritonitis, particularly in patients with CD4 count <200 cells/mm³, and in the other study, HIV was not identified as an independent risk factor for peritonitis [41,42].

COMPLICATIONS OF END-STAGE KIDNEY DISEASE — The management of people living with HIV (PWH) with end-stage kidney disease (ESKD) also involves treatment of common complications of advanced chronic kidney disease (CKD), including anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD).

Anemia — Anemia in PWH with ESKD is frequently multifactorial and may result from erythropoietin deficiency, opportunistic infections, and drug-induced myelosuppression, although the last is rare with newer antiretroviral agents [43]. (See "Treatment of anemia in nondialysis chronic kidney disease" and "Hyporesponse to erythropoiesis-stimulating agents (ESAs) in chronic kidney disease".)

Chronic kidney disease-mineral and bone disorder — HIV infection and antiretroviral therapy (ART) are associated with loss of bone mineral density, and the commonly used antiretroviral agent tenofovir disoproxil fumarate has been associated with alterations in parathyroid hormone and other markers of bone mineral metabolism (see "Bone and calcium disorders in patients with HIV"). The impact of the alternative prodrug tenofovir alafenamide on bone health has not been evaluated among patients on maintenance hemodialysis. Although there are no contemporary studies specifically evaluating disordered mineral and bone metabolism in PWH with advanced CKD or ESKD, underlying bone disease may complicate the management of CKD-MBD. (See "Management of hyperphosphatemia in adults with chronic kidney disease", section on 'Patients on dialysis' and "Management of secondary hyperparathyroidism in adult patients on dialysis".)

ANTIRETROVIRAL THERAPY — The use of antiretroviral therapy (ART) is the single most important intervention for people living with HIV (PWH), with or without end-stage kidney disease (ESKD). HIV treatment guidelines from the Department of Health and Human Services recommend initiation of ART in all persons diagnosed with HIV infection, regardless of CD4 cell count [44]. A detailed discussion of the use of ART in PWH can be found elsewhere (see "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach"). Consistent with evidence in the nondialysis population with HIV infection, ART provides substantial survival benefits among PWH with ESKD [45-50], as discussed in detail below.

Observational data suggest that ART is also beneficial in HIV-associated nephropathy (HIVAN), including cases with dialysis-dependent kidney failure [19,20]. In several case reports, patients with HIVAN and dialysis-dependent kidney failure became dialysis free after initiating ART [19,20]. Repeat kidney biopsy also revealed significant histologic improvement in the cases that underwent repeat biopsy [51].

The selection and dosing of antiretroviral drugs in patients with kidney disease are discussed in detail separately. Inappropriate dosing of ART is common in patients on dialysis and may be associated with inadequate virologic control, medication toxicity, and increased mortality [52,53]. A small number of single-tablet regimens are now approved for use in patients on hemodialysis. Long-acting injectable regimens also are approved for use in patients on hemodialysis. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Overview of antiretroviral agents used to treat HIV".)

PROGNOSIS — Mortality of patients with acquired immune deficiency syndrome (AIDS) treated with dialysis in the 1980s was extremely high, approaching 100 percent at one year [54]. By comparison, subsequent studies have reported improved survival of people living with HIV (PWH) on dialysis after the introduction of effective antiretroviral therapy (ART) [46-49]:

●Trends in the mortality of over 14,000 individuals with ESKD attributed to HIVAN were assessed in United States Renal Data System (USRDS) data from 1989 to 2011. Compared with those who initiated dialysis between 1989 and 1992, mortality declined by 40 percent among those initiating dialysis in 1999 to 2000, and by 64 percent among those who started dialysis in 2009 to 2011 [17].

●In a study of African-American patients on dialysis from the USRDS, one-year survival increased from 47 percent during 1990 to 1994 to 65 percent during 1995 to 2001 [48]; five-year survival also increased from 13 to 30 percent.

●A prospective cohort study from France reported similar survival (approximately 89 percent) among 164 PWH on hemodialysis and 584 patients on hemodialysis without HIV or diabetes [49].

●In contrast, a large, single-center cohort study of African-American end-stage kidney disease (ESKD) patients in Baltimore, Maryland failed to demonstrate an improvement in survival with the advent of ART, possibly reflecting inadequate ART in this urban population [55].

●A 2017 analysis of data from a large United States dialysis provider demonstrated higher mortality among patients with HIV-hepatitis C virus coinfection compared with HIV-negative patients. HIV monoinfection was also associated with higher mortality among Black patients on dialysis [16].

Long-term exposure to ART has been associated with an increased risk of cardiovascular disease in PWH on dialysis [56]. Regimens containing protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs), in particular, have been associated with metabolic abnormalities and endothelial dysfunction, and increasing exposure to specific agents has been associated with an increased risk of myocardial infarction in large cohort studies [57-61]. While the NRTI abacavir has received the most attention [58,59,61], pooled data from premarketing clinical trials of abacavir did not demonstrate any excess risk [62], and data from a large, collaborative cohort study have also implicated several other ART agents [60]. The potential for additive cardiovascular risk in patients with ESKD should be balanced against the well-established benefits of ART.

TRANSPLANTATION — With improved survival and better long-term prognosis, kidney transplantation has emerged as an important consideration in people living with HIV (PWH) with end-stage kidney disease (ESKD). The potential for significant interactions between calcineurin inhibitors and antiretroviral therapy (ART) requires close communication between the transplant team and HIV providers. Kidney transplantation in PWH is discussed in detail separately. (See "Kidney transplantation in adults: Kidney transplantation in patients with HIV".)

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: Dialysis".)

SUMMARY AND RECOMMENDATIONS

●Prevalence – The prevalence of human immunodeficiency virus (HIV) infection in patients on dialysis is difficult to estimate and appears to vary in part based on the local HIV seroprevalence. (See 'Epidemiology' above.)

●HIV testing – We recommend voluntary, confidential HIV testing of all patients on dialysis. Potential benefits of routine screening include improved patient survival, possible reversal of HIV-associated nephropathy (HIVAN), and implementation of measures to prevent transmission to partners. (See 'Human immunodeficiency virus testing' above.)

●Transmission of HIV in the dialysis unit – HIV transmission in the dialysis setting, which is rare, can be avoided by strict adherence to standard infection-control procedures. In agreement with the Centers for Disease Control and Prevention (CDC), we feel that no special isolation of people living with HIV (PWH) on dialysis is necessary. (See 'Transmission in the dialysis unit' above.)

●Antiretroviral therapy – The use of antiretroviral therapy (ART) is the single most important intervention for PWH. ART is associated with the reversal of HIVAN and with decreased mortality in patients on dialysis. However, inappropriate dosing of ART is common in patients on dialysis and may be associated with inadequate virologic control or with medication toxicity. (See 'Antiretroviral therapy' above and 'Prognosis' above.)