indinavir-sulfate and Mycobacterium-avium-intracellulare-Infection

Effective antiretroviral therapy leads to rapid decrease in plasma HIV-1 RNA, frequently followed by an increase in CD4 T-helper cell counts. The improvement of immune function during highly active antiretroviral therapy has important impact on natural history of AIDS-related opportunistic disorders. Here we describe cases of unusual clinical inflammatory syndromes in CMV retinitis, hepatitis C, and atypical mycobacteriosis in HIV-1 infected patients associated with the initiation of antiretroviral therapy. Pathogenetic implications and therapeutic management of these new immunopathologic syndromes are discussed.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cytomegalovirus Retinitis; Female; Hepatitis C; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Lamivudine; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Reverse Transcriptase Inhibitors; Zidovudine

Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant increases in CD4 T-helper lymphocyte counts. The main side-effects of the protease inhibitors currently in use include gastrointestinal disturbances, paraesthesias, hyperbilirubinaemia, and nephrolithiasis. The increasing use of these agents in patients with advanced HIV-1 infection and CD4 counts of less than 50 cells/microL may be associated with unforeseen adverse effects not observed in earlier studies of patients with higher CD4 counts.. Five HIV-infected patients with baseline CD4 lymphocyte counts of less than 50 cells/mL were admitted to the Beth Israel Deaconess Medical Center (Boston, MA, USA) with high fever (> 39 degrees C), leucocytosis, and evidence of lymph-node enlargement within 1-3 weeks of starting indinavir therapy. Informed consent was obtained for studies that entailed CD4 lymphocyte counts, immunophenotyping, isolator blood cultures, and radiological scans. Biopsy samples of cervical, paratracheal, or mesenteric lymph nodes were taken for culture and pathology in four patients.. Lymph-node biopsy samples showed that focal lymphadenitis after initiation of indinavir resulted from unsuspected local or disseminated Mycobacterium avium complex (MAC) infection. The prominent inflammatory response to previously subclinical MAC infection was associated with leucocytosis in all patients and with an increase in the absolute lymphocyte counts in four patients. Three patients with follow-up CD4 counts showed two-fold to 19-fold increases after 1-3 weeks of indinavir therapy. Immunophenotyping after therapy in two patients showed that more than 90% of the CD4 cells were of the memory phenotype.. The initiation of indinavir therapy in patients with CD4 counts of less than 50 cells/mL and subclinical MAC infection may be associated with a severe illness, consisting of fever (> 39 degrees C), leucocytosis, and lymphadenitis (cervical, thoracic, or abdominal). The intense inflammatory reactions that make admission to hospital necessary may be secondary to significant numbers of functionally competent immune cells becoming available to respond to a heavy mycobacterial burden. Prophylaxis or screening for subclinical MAC infection, or both, should therefore be done before the beginning of protease-inhibitor therapy in patients with advanced HIV infection.

Topics: Adult; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Tuberculosis, Lymph Node

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Bacteremia; Didanosine; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Indinavir; Male; Mycobacterium avium-intracellulare Infection; Reverse Transcriptase Inhibitors; Zidovudine

A case study is presented of a 27-year-old male, in the late stages of AIDS, who benefitted from recent advances in HIV therapy. During recovery from his fourth episode of pneumocystis pneumonia and newly-diagnosed disseminated Mycobacterium avium (MAC) infection, he agreed to take antiretrovirals. He received treatment with indinavir, Epivir, and stavudine, and then had stavudine replaced with AZT due to adverse effects. He also received treatment for MAC. His diarrhea and fevers disappeared, his appetite returned, and he gained 50 pounds. A tinea infection on his back and face resolved, as did persistent oral candidiasis. Although HIV myelitis was suspected during treatment, it stabilized, or even improved. The patient became discouraged when his viral load rose from 2,100 to 5,700, and trying to make him understand that his initial loads were probably near a million copies did not reassure him. Referral to a clinical psychologist seemed to help, and he continues to do well on therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Counseling; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Male; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis; Reverse Transcriptase Inhibitors; Stavudine; Treatment Outcome; Zidovudine