1 Hennepin County Medical Center and the University of Minnesota Minnesota, USA 2 Johns Hopkins University School of Medicine, Maryland, USA
Sir,
Progression from infection with the human immunodeficiency virus (HIV) to acquired immunodeficiency syndrome (AIDS) is a complex process, with plasma viral load the most reliable predictor of progression [1,2]. Immune activation of the host, with increased levels of proinflammatory cytokines such as tumor necrosis factor-, interleukin (IL)-1, IL-6, and IL-8 is associated with increased viral replication and an accelerated course of HIV-induced disease [1]. During haemodialysis, contact between blood and the dialysis membrane stimulates the production of proinflammatory cytokines including IL-1, IL-6, IL-8, and TNF-
[3]. The use of dialysis membranes, called biocompatible, may minimize these undesirable extra corporal events. As haemodialysis stimulates the production of cytokines known to activate HIV replication, haemodialysis, therefore, may increase viral load. We therefore examined the effect of a single haemodialysis treatment on viral load in two HIV-infected patients.
Cases. Patient #1 was a 34-year-old homeless African American female with end-stage renal disease secondary to hypertension and diabetes mellitus who initiated haemodialysis 2 years prior to these HIV quantitations. She had been diagnosed as HIV positive 5 years earlier but did not comply with recommended follow-up. Her HIV risk factor was unprotected heterosexual activity with an HIV-infected partner. Her CD4 count at the time of the study was approximately 300/mm3. Patient #2 was a 33-year-old African American male with end-stage renal disease presumed secondary to HIV nephropathy. He had initiated haemodialysis 3 months prior to these measurements of his HIV viral load. The patient had been diagnosed as HIV positive by serology when he presented with unexplained renal failure, 3 months earlier. His HIV risk factors were a history of i.v. drug abuse and unprotected bisexual activity. His CD4 count was approximately 300/mm3. Neither patient was taking antiretroviral medications at the time of the study.
The amount of HIV found in the plasma of these HIV-infected patients was determined prior to and upon the completion of a routine haemodialysis. Plasma HIV RNA was quantitated using a quantitative reverse transcriptase-polymerase chain reaction kit (Roche, Indianapolis, IN, USA). The laboratory reports an intra-assay variability of up to 20% with this assay. The pre-haemodialysis and post-haemodialysis samples were analysed side-by-side. Initially both patients were dialysed with a cellulose acetate membrane (Baxter model CA-210, Deerfield, IL, USA). Between 4 and 6 weeks later, the same measurements were repeated except that the patients were dialysed for the single treatment with a more biocompatible polysulfone membrane (Fresenius model F8, Lexington, MA, USA).
Haemodialysis with a cellulose acetate membrane resulted in a doubling of the amount of HIV detected in the plasma of patient #1 (Figure 1). This corresponds to a log increase of 0.31. Haemodialysis caused a 4.6-fold increase in the viral load of patient #2, a log increase of 0.67. When the same patients underwent haemodialysis using a polysulfone membrane, there was little change in their plasma HIV concentration (Figure 1
).
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These preliminary results suggest that HIV-infected, end-stage renal disease patients not on antiretroviral therapy should be haemodialyzed with the more biocompatible membranes to prevent dialysis-induced increases in plasma viral load and possible acceleration of disease. An earlier study, using a cellulose acetate membrane, showed a small reduction (45% or 0.3 log) in plasma HIV levels after the haemodialysis of 10 HIV-infected patients [7]. However, these patients were taking one to three different antiretroviral medications. The authors Ahuja et al. speculated that the reduction was the result of a non-specific adsorption of the viral RNA to the dialysis membrane because HIV RNA could not be detected in the ultrafiltrate. A significant difference between their study and the observations presented here is that the patients studied by Ahuja et al. all were taking antiretroviral medications. These medications would blunt the effect of the inflammatory cytokines on viral replication by inhibiting viral replication. Therefore, the choice of a biocompatible dialysis membrane for an HIV+ end-stage renal disease patient may not be as critical if the patient is on antiretroviral therapy. Our results suggest the need for prospective studies evaluating HIV viral load and patient outcome in haemodialysis patients, particularly focusing on the effects of the type of dialysis delivered.
Notes
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