Persistence of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte clones in a subject with rapid disease progression.

We longitudinally measured T-cell receptor transcript frequencies of human immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) in an individual with rapidly progressive disease and high levels of viremia. CTL clones elicited during acute HIV-1 infection were present at the time of death, despite absent functional CTL responses, arguing against clonal deletion as a mechanism for the decline of CTL responses observed during HIV-1 infection.

Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection.

Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory cytotoxic T-lymphocyte (CTL) responses, and viral sequence variation were performed on a patient who presented with acute HIV-1 infection, developed an AIDS-defining illness 13 months later, and died 45 months after presentation. Neutralizing-antibody responses remained weak throughout, and no HIV-1-specific lymphocyte proliferative responses were seen even early in the disease course. Strong in vivo-activated CTL directed against Env and Pol epitopes were present at the time of the initial drop in viremia but were quickly lost. Memory CTL against Env and Pol epitopes were detected throughout the course of infection; however, these CTL were not activated in vivo. Despite an initially narrow CTL response, new epitopes were not targeted as the disease progressed. Viral sequencing showed the emergence of variants within the two targeted CTL epitopes; however, viral variants within the immunodominant Env epitope were well recognized by CTL, and there was no evidence of viral escape from immune system detection within this epitope. These data demonstrate a narrowly directed, static CTL response in a patient with rapidly progressive disease. We also show that disease progression can occur in the presence of persistent memory CTL recognition of autologous epitopes and in the absence of detectable escape from CTL responses, consistent with an in vivo defect in activation of CTL.

Pseudo-Cushing's syndrome in human immunodeficiency virus-infected patients.

To our knowledge, an association between human immunodeficiency virus infection and pseudo-Cushing's syndrome has not previously been described. We describe four HIV-infected patients with pseudo-Cushing's syndrome, characterized by striking dorsocervical and submandibular fat accumulation and central obesity. In each case, cortisol levels were either normal or suppressed adequately with administration of dexamethasone, excluding the diagnosis of true Cushing's syndrome. Immune function and weight improved significantly preceding the development of pseudo-Cushing's syndrome. Three of the four patients were taking a common protease inhibitor at the onset of symptoms, and the fourth reported the exacerbation of his symptoms with the addition of a protease inhibitor. The observed characteristic pattern of fat deposition may be attributable to a specific effect of new antiretroviral therapies or may relate to recovery independent of medication usage. Distinguishing between pseudo-Cushing's syndrome and true Cushing's syndrome is critical for preventing the unnecessary and potentially harmful treatment of such patients. Further research into the mechanisms of this novel phenomenon is needed.

Adjunctive corticosteroid therapy for patients whose treatment for disseminated Mycobacterium avium complex infection has failed.

Patients with AIDS and disseminated Mycobacterium avium complex (MAC) infection can have progressive disease despite combination antimycobacterial therapy. Our goal was to determine the utility of corticosteroids as adjunctive therapy for AIDS patients with disseminated MAC infection and refractory symptoms despite combination antimycobacterial therapy. We retrospectively reviewed 12 consecutive patients whose therapy for MAC infection clinically failed and who subsequently received low-dose oral corticosteroids in addition to continued combination antimycobacterial therapy. With the addition of corticosteroids, 11 of 12 patients experienced a rapid improvement in symptoms, with diminished or resolved fevers and night sweats, and an increased sense of well-being and energy. Ten of 12 patients gained weight; the differences between weights before and after steroid therapy were statistically significant (P = .003, paired Student's t-test), and the weights achieved were similar to baseline weights prior to the development of MAC infection (P = .2). Mean survival after diagnosis of MAC infection was 17.5 months. New opportunistic processes developed in seven patients during corticosteroid therapy. However, given the severely immunocompromised status of these patients, it was not possible to attribute the development of new opportunistic processes directly to corticosteroid therapy.