TREATMENT OF HIV-1-ASSOCIATED MICROSPORIDIOSIS AND CRYPTOSPORIDIOSIS WITH COMBINATION ANTIRETROVIRAL THERAPY

Background Enterocytozoon bieneusi and Cryptosporidium parvum? cause c hronic antimicrobial-resistant gastrointestinal infections in HIV-1-in fected individuals. HIV-1 reverse transcriptase inhibitors delay the o nset of opportunistic infections, but are not known to reverse: establ ished infections. HIV-1 protease inhibitors are more effective across a broader range of HIV-l-infected immune cells. Combination antiretrov iral[ therapy that includes a protease inhibitor could improve immunit y to E bieneusi and C:parvum, Methods HIV-1 infected patients with chr onic microsporidiosis (five), cryptosporidiosis (three), or dual infec tion lane), were treated with combination therapy that included at lea st one HIV-1 protease inhibitor, Outcome measures were symptoms weight , use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia! stool microscopy, and biopsy by endoscopy. Findings A il patients had complete clinical responses, gained a median 15 hg in weight, and ceased ail antidiarrhoeal and antimicrobial therapies, Bil iary cryptosporidiosis responded in both affected patients, Neither pa thogen was detected in follow-up stool microscopy (eight of eight pati ents) or in biopsy samples by endoscopy (five of five), Intestinal arc hitecture returned to normal in three patients, There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-gamma before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41., Fi ve patients remained symptom-free after a median 13 months' follow-up, Four patients had recurrent diarrhoea at 7-13 months (one with positi ve stool microscopy), associated with declining CD4 counts. Interpreta tion Combination antiretroviral therapy that includes a protease inhib itor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and his tological responses, The persistent CD8 cell and macrophage infiltrate , and the rapid time to relapse in patients with declining CD4 lymphoc yte counts, suggest that neither infection was eradicated.