INTRODUCTION



Current antiretroviral therapy has allowed for an increased survival  of  patients  infected  by  the  human  immunodeficiency virus (HIV).1 This increase has led to the occurrence of  other  associated  complications  that were  less  common 15  years  ago.2 From  the  nephrological  perspective,  an  increase  has  occurred  in  HIV patients  with  renal  involvement, and their prognosis in renal replacement therapy has changed  favorably3,4 as  compared  to  the  beginning  of  the 90s, when early studies reported high mortality and complication  rates.5,6 There  is  currently  no  controversy  about  inclusion of  these patients  in a hemodialysis (HD) or peritoneal dialysis (PD) program when they need it, The situation of  these  patients  on  PD  has  progressed  over  these  years, and the most determinant factor today is the HIV disease itself.7 The course over  time and  the  characteristics of HIV-positive patients  in our PD program from 1995  to date are reported.



METHODS



From November 1995  to November 2007, data were  retrospectively  collected  from  all HIV-infected  patients who had started renal replacement therapy using peritoneal dialysis at our  center. Demographic  and  laboratory  data  of  all  patients were  reviewed. The  survival curve was calculated using  the Kaplan-Meier method. Patients who were switched to another replacement  treatment  modality  (HD  or  kidney  transplant) were  considered  lost  for outcome purposes. Outcomes were compared using a Student¿s t test for paired data. Means and medians  are  given  with  their standard  deviation  and  range respectively. A value of p < 0.05 was considered statistically significant.



RESULTS



Eight patients, seven males and one female, were included in this  period. All  patients were  Caucasian. Mean  patient  age was  40,7 ± 5,3  years. The  different  underlying  diseases  are given in Table 1. Six patients had stage C3 HIV infection, one stage B3, and  the other  stage B2 HIV infection. Serological testing for HCV was positive in all patients, but only one pa- tient had data suggesting chronic liver disease. They all were former intravenous drug users.



Mean  follow-up  time  on  PD  was  41.2  ± 32,1  months, with  a  median  of  29,5  months  (range:  12-103).  Survival rates at one,  two, and  three years were 100%, 62.5%, and 50% respectively, as may be seen in Figure 1, with an overall mortality at study end of 62.5%. Five patients died, two from ischemic heart disease, a third patient from fulminant gangrene in his right leg caused by Pseudomonas aeruginosa,  a  fourth  patient  died  at  home  for  an  unknown  reason, and  the  final  patient  died  from  sclerosing  peritonitis  after six years on PD. A patient was switched to HD after peritonitis  induced by Mycobacterium fortuitum, another patient received a kidney transplant after 9 years on dialysis, and a final patient continued on PD at study completion (table I). Table II compares the survival rates reported by studies involving HIV patients on peritoneal dialysis, showing an increased  survival  and  a  decrease  in  complications  over  the years.



Complications of the procedure

The infectious peritonitis (IP) rate and the number of hospitalizations were 0.36 IP/year and 0.69 admissions/year respectively. Staphylococcus epidermidis was the most common causative organism, but was only found in two patients. A patient experienced  six  IP episodes  (two  from  Klebsiella pneumoniae,  two from Staphylococcus epidermidis, one sterile peritonitis, and one from Pseudomonas fluorescens). Another patient  experienced  an  IP by  Mycobacterium fortuitum that required  removal of his peritoneal catheter and  switching  to HD. In another case with a good outcome, the identified germ was  Escherichia coli,  and  IP induced  by Candida albicans occurred in a single case. Three patients suffered no peritonitis during this study period, one of them probably because of his short time on PD (12 months). A second patient continues on PD after 32 months, and the remaining patient received a kidney transplant after almost nine years on PD. Only 15.7% of hospital admissions were caused by an infectious peritonitis. The most common  reason  for admission was  respiratory tract infection.



Course of HIV infection

All patients were on antiretroviral therapy. Although different schemes were  used,  all  patients  but  one were  on  triple  therapy.  Among  nucleoside  reverse  transcriptase  inhibitors (NRTIs), the most commonly used drug was lamivudine (Epivir®) taken by 75% of patients. Thus, the most usual combination consisted of lamivudine plus stavudine (Zerit®), found in half the cases. These drugs were normally associated to a protease  inhibitor  (PI).  Both  stavudine  and  abacavir  (Ziagen®) were taken by 62.5% of patients. The most commonly used PI was  nelfinavir  (Viracept®),  received  by  37.5%  of  patients. Non-nucleoside  reverse  transcriptase  inhibitors (NNRTIs) were  scarcely used, and only one patient  received efavirenz (Sustiva®)  in his  treatment. From  the clinical viewpoint, patients maintained a good viral response. None of the five patients with an undetectable viral  load experienced any changes in viral load, that decreased to undetectable levels in the other  three patients. CD4  levels  increased  in all patients but one. Mean CD4 percentage was 20.2% at baseline and 23.5% at one year, but this increase was not statistically significant. Another aspect assessed was weight gain (net weight), based on  the  assumedly  greater malnutrition  in PD  due  to  protein loss in peritoneal fluid. No differences were found in our patients  in  serum  albumin  levels  or  nPCR,  but  a  significant weight gain was  seen  in  the  first year. Mean patient weight was 60.6 ± 8 kg at baseline and 64.9 ± 10 kg at one year, p = 0.016 (fig. 2).



DISCUSSION



Our  study  confirms  an  increased  survival  of HIV patients on peritoneal dialysis. Survival rates at one, two, and three years were similar to another recent study3 and higher than the rates reported by Tebben and Kimmel.5,6 Early studies on HIV patients  with  end-stage  renal  disease  (ESRD)  and renal  replacement  therapy  by  Ortiz,8 Perinbasekar,9  and Feinfeild10 reported a poor outcome. New highly active antiretroviral  therapy  (HAART)  has  led,  particularly  since 1995,  to  a marked  increase  in  life  expectation1 which  has allowed for survival rates in peritoneal dialysis longer than 5  years,  and  up  to  9  years  in  our  experience.3 However, mortality  continues  to  be  high  in  these  patients  despite more  effective  treatments.3,4 Survival  of  HIV-infected  patients  has  improved,1 and  does  not  change  irrespective  of the  renal  replacement  therapy  used.7 Rodríguez  et  al,  in

their study on 100 HIV-infected patients, showed that those who  started  dialysis  in  the  pre-HAART era  survived  9.4 months, while patients starting dialysis  in  the HAART era survived 16.1 months. However, the corresponding figures for all HIV-positive patients not on dialysis were 16 and 81 months.11 Other studies suggested an inadequate antiretroviral treatment in patients on renal replacement therapy.12 However,  an  analysis  of  the  different  studies  involving HIV-infected  patients  on  PD  showed  an  improved  survival, particularly when the two pre-HAART studies were compared  to  studies  conducted  in  the HAART era,  from  a mean survival of 17.9 months to longer than 40 months (table II).



From  the  therapeutic  viewpoint,  there  are  studies  and guidelines with recommendations for antiretroviral therapy in ESRD  and  dialysis,  but ART in PD  is  not  clearly  defined.13 Szczech reviewed  this aspect  in 89 HIV-positive patients,  five  of  them  on PD,  and  found  that  the most  commonly used drug was  lamivudine,  in 36 patients,  followed by  stavudine  in  33  patients  and  nelfinavir  in  21  patients. These results were similar to those seen by our study group. These data are consistent with the widespread use of stavudine and nelfinavir during  the  final 90s and  the beginning of  the  2000  decade,  the  period  mostly  described  in  our study. These drugs are now used as first-line treatment because  of  their  low  potency  (nelfinavir)  or  high  associated toxicity  (stavudine).14,15 Currently,  and  until  studies  providing new indications are available, it appears reasonable to

take the same measures as in hemodialysis, considering the special characteristics of these patients on PD.16,17



Complications of  the procedure have decreased  in parallel  to  the  increase  in  survival. Thus,  infectious peritonitis rates in HIV patients have decreased from 3.9 and 2.4 episodes/year  in  early  studies  to  1.4  episodes/year  in  the Khana  study  or  0.3  episodes/year  in  our  study,4.6 though some  studies have  reported  conflicting  results. Thus, Tebben et al6 found  in a group of 39 patients a higher number of peritonitis  in HIV-infected patients, and Scholoth18 also noted in 9 similar patients a higher rate of infectious peritonitis, as did Khana.4 Other  authors  showed  no  differences between  both  groups.5,19 In  our  study,  peritonitis  rate was

not different from the rate seen in non-HIV-infected population in our unit.



Although opportunistic  infections have been  reported  in HIV patients  treated with PD, Gram-positive cocci are  the most  common  cause  of  infectious  peritonitis.6,20-22 Our  results are very similar to those of the Kimmel group, with a case  each  of  IP caused  by  Pseudomonas and Mycobacterium. Fungal involvement was seen in a single patient, and there were no cases of polymicrobial peritonitis. 23 It should be noted that 6 of the 10 episodes of peritonitis occurred in the same patient, and three patients experienced no IP while on  peritoneal  dialysis,  in  contrast  to  other  studies  where 100% of patients experienced some episode of  IP.5 Course of peritonitis in our study was usually favorable, and removal  of  peritoneal  catheter was  only  required  in  two  cases. Hospitalization  rate was also  low as compared  to previous studies.3-4



These results are possibly conditioned by advances in antiretroviral therapy, a decreased viral load, and an improved immune status, which are known good prognostic factors.24-26 In our study, all patients were on HAART, viral load was low or undetectable in most cases, and the CD4 percentage was  adequate. Although higher  serum  albumin  levels3 and an  increased  risk  of  peritonitis  associated  to  them27 have been  reported  in  PD,  this  does  not  appear  to  result  in  a lower survival in HIV patients.5 While no changes in serum albumin  levels or nPCR were  found  in our patients, an  increase  in  net  weight  was  shown,  at  least  during  the  first year. However,  62%  of  patients were  hypertensive  at  PD start,  and  two  patients  died  from  coronary  disease.  Some drugs, such as lopinavir, have been associated to an increase  in  systolic blood pressure,28 other drugs  such as  fosamprenavir29 to a lipid-lowering effect, and still others such as ritonavir  have  been  associated  to  both  effects.30 NNRTIs and PIs usually have a poorer lipid profile and a higher risk of  associated  coronary disease.31-33 Association of  risk  factors may be determinant for a decreased overall survival in these patients.



On  the other hand,  increased prevalence of  these patients raises therapeutic alternatives that were unthinkable not long ago. Thus, kidney transplant is a valid option if the following requirements are met: HAART, undetectable viral load, CD4 count above 200 cells/mm3, and absence of recent opportunistic  infections.25,34,35 In  our  case,  a  patient meeting  the  above criteria received a kidney transplant with an excellent outcome. Long-term outcome in these kidney transplant patients is unknown, but  short and mid-term course appears  safe, or at least with a similar survival to other risk groups.36,37



In conclusion, while our study has the limitations inherent to a retrospective study on a small patient sample, it showed  an  improved  survival  and  low  rates  of  infectious peritonitis and hospitalization. Adequate  treatment of HIV infection  and  other  associated  diseases  conditions  the  current outcome of the procedure, which is similar to the non-HIV population in our study. Immune status does not appear to change in PD, and adequate nutrition is possible. PD is therefore a treatment of choice for these patients. Until greater experience and additional studies are available, individualized  and multidisciplinary  control  appears  reasonable in these patients.