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A substantial number of patients with advanced HIV infection suffer from intractable diarrhoea. The aim of this study was to evaluate whether potent antiretroviral therapy could alleviate such diarrhoea.In an open randomized study the effect of the HIV protease inhibitor indinavir in combination with nucleoside analogue reverse transcriptase inhibitors on chronic HIV-related diarrhoea was investigated in 14 late-stage (CD4+ lymphocyte count ≤ 50 × 106 cells/l) HIV-infected patients. Data concerning stool frequency, stool consistency and antidiarrhoeal drug use were collected in daily diaries over a 24-week period. Endpoints of the study were reduction of stool frequency, improvement of stool consistency, weight gain, and in case of diarrhoea due to Enterocytozoon bieneusi or Cryptosporidium sp. disappearance of these parasites from stool.Thirteen patients started the study drug indinavir. One patient died after 1 week and one patient withdrew prematurely after 18 weeks. Median stool frequency declined from 5.8 daily at baseline to 2.3 daily after 24 weeks (P = 0.04). Stool consistency improved considerably over the study period: before treatment 56% of stools were watery and 0% were formed; at week 24 these figures were 0 and 35%, respectively. Body weight increased significantly with a median increment of 6.6 kg at week 24 (P = 0.0006). In two out of six patients with microsporidiosis and both patients with cryptosporidiosis, stools were free of parasites at week 24. Five out of six patients who used non-specific antidiarrhoeal medication on a regular basis prior to the study had ceased to do so at the end.The use of potent antiretroviral therapy in patients with advanced HIV infection can improve chronic HIV-related diarrhoea and in some cases lead to disappearance of E. bieneusi and Cryptosporidium sp. from the stools.