final program.qxd - Parallels Plesk Panel

PP 3.39
Faecal flora, diarrhoea associated with protease inhibitors in HIV-infected patients
F. de Salvador-Guillouët, H. Carsenti-Dellamonica, X.Hebuterne, F.Girard-Pipau,
J. Durant, P.Dellamonica
Hôpital de l'Archet 1- service Infectiologie - BP 3079 - 06202 Nice cedex 3
Diarrhoea and abdominal pain with varying degrees of severity are frequent in HIVinfected
patients and diarrhoea is one of the main causes of alteration of patients' quality
of life.
Objectives
the aim of our study was to explore intestinal disorders associated with nelfinavir, a
protease inhibitor (PI).
Methods
A prospective open study was conducted and included: 5 individuals with stool samples
before and after treatment with nelfinavir (two healthy subjects and 3 HIV-infected
patients), one untreated HIV-infected patient, 9 on treatment with nelfinavir during 1 month
to 1 year and with varying degrees of intestinal dysfunction. A total of 20 stool samples
were available and immediately frozen at -20°C (within less than 2 hours)
Patients gave their informed consent Known bacterial or parasitic causes of diarrhoea
were ruled out.
Methods
samples were analyzed for faecal flora by a gel-separation procedure for double stranded
deoxyribonucleic acid (TGGE) and proteolytic activity was expressed as log10 of trypsin
units that hydrolysed azocaseine per hour and per gram of faeces and determined in
crude homogenate and soluble fraction.
Results
For treated HIV-infected patients, similarity percentage for TGGE before and after
treatment was 86.7%. TGGE profiles were already disturbed and looked abnormal at the
initial TGGE analysis study. PI did not appear to change the faecal flora significantly.
Similarity percentage indicated a disturbance in faecal flora only in healthy subjects who
took the treatment during three weeks. They did not have any diarrhoea, only soft stools.
Proteolytic activity was enhanced in PI-naïve HIV-infected patients (9.4+3.6 and 4.5+2.0
logTrypsine U/ml) and decreased after = 2 months' nelfinavir treatment (6.3+1.4 and
2.6+0.08 logTrypsine U/ml) in crude homogenate and soluble fractions, respectively. The
level of proteolytic activity was similar to that of healthy patients only after more than one
month's treatment
Conclusion
this pilot study concerns a small number of samples due to difficulties in obtaining fresh
stool samples. However HIV-infected patients appear to have a major disturbance of their
faecal flora with high proteolytic activity prior to treatment that decrease after PI treatment.
Our study suggests that an independent factor may have altered the flora before both
samples were taken. Such elevated levels of faecal proteases in this disease may play a
role in subsequent damage of the intestinal mucosa. These preliminary results merit
further investigation.
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