Journal of acquired immune deficiency syndromes最新文献

This study determined the in situ detection rate of polymerase chain reaction (PCR)-amplified human immunodeficiency virus type 1 (HIV-1) DNA and RNA in lymph nodes and peripheral blood CD4+ cells in six patients with asymptomatic HIV-1 infection and from six people who died of advanced AIDS. The lymph nodes of patients with asymptomatic infection showed expanded germinal centers where, on average, 20% of the CD21+ dendritic cells contained HIV-1 DNA. From 5 to 80% of the CD4+ cells in these lymph nodes contained HIV-1 DNA, as compared with 1-11% of the CD4+ peripheral blood mononuclear cells. The infection in most cells was latent in the asymptomatic group. In contrast, the lymph nodes of patients with advanced AIDS showed marked depletion of both dendritic and CD4+ cells. The majority of the remaining CD4+ cells in the lymph nodes and blood showed PCR-amplified viral DNA and cDNA sequences suggesting the presence of genomic and multiple spliced transcripts. It is concluded that asymptomatic HIV-1 infection is associated with a wide range of latent to active viral-positive CD4+ lymphocytes and dendritic cells in the lymph nodes. Progression to AIDS is characterized by active viral replication in many of the remaining CD4+ cells in the lymph nodes and blood.

The aim of this study was to ascertain the safety profile of didanosine (Videx; ddI) within the Canadian Open Treatment Program. Symptomatic HIV+ subjects with AIDS or ARC or CD4 < 200/mm3 were eligible to receive didanosine if they were either (a) intolerant to zidovudine (Retrovir, ZDV) or (b) deteriorating despite ZDV therapy. The dose of didanosine (powder formulation) was based on body weight as follows: > or = 75 kg, 375 mg b.i.d.; 50-74 kg, 250 mg b.i.d.; 35-49 kg, 167 mg b.i.d. Participants were monitored with physical examinations and prespecified laboratory studies by their treating physicians on a monthly basis. Follow-up data were collected in a central database through five regional coordinators. A total of 168 physicians across Canada participated in the program, and 825 subjects who started didanosine after July 1, 1990, were included in the analysis. Of these, 97% were male, 88% homosexual, and 59% had a prior diagnosis of AIDS. Reasons for enrolling was ZDV intolerance in 39%, failure in 25%, both in 32%, and other in 4%. Data were prospectively collected until July 31, 1991. Total follow-up was 3,440 patient-months and median follow-up was 4.3 months. A total of 78 deaths were reported, 44 of which occurred within a month after the last dose of didanosine. Causes of death included AIDS-related unspecified causes (13 patients), MAC (11), wasting (7), AIDS-related CNS involvement other than OI's (7), Kaposi's sarcoma (7), Pneumocystis carinii pneumonia (6), sudden death, including suicides and accidents (6), lymphoma (5), toxoplasmosis (4), cryptococcosis (4), cytomegalovirus (3), unspecified causes (2), tuberculosis (1), PML (1), and disseminated histoplasmosis (1). Didanosine was discontinued in 140 (17%) subjects during the study period due to adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV-1 envelope glycoprotein (gp120) may contribute to the magnitude of the immunological defects observed in the early stages of HIV-1 infection by modulating CD4 from the cell surface and altering the function of both CD4 and CD3 in uninfected cells. We investigated CD4 expression as well as CD3- and CD4-mediated cell migration in normal peripheral blood T lymphocytes exposed to recombinant gp120 in long-term cultures for < or = 6 days. Single low doses of gp120 (0.5 microgram/ml) modulated CD4 by 4-6 h, reached a nadir at 24-72 h, and began to recover at 96 h. By day 6, surface expression of CD4 had rebounded to control levels. CD3 expression was unchanged at all time points. Concomitant with loss of surface CD4 was significant lessening of both anti-CD4 and anti-CD3 antibody-induced migration. Reexpression of CD4 at 96 h resulted in the recovery of both CD4- and CD3-mediated migration. Cycloheximide inhibited CD4 reexpression and both anti-CD4 and anti-CD3 antibody-induced migration in cells treated with gp120. These data suggest that CD4 modulation by gp120 results in loss of function, which persists until new membrane CD4 is generated. Persistent exposure of CD4+ cells to gp120 in vivo may contribute to the disproportionately large immunological deficits seen in the early stages of HIV-1 infection, in which most CD4+ cells remain uninfected.

During a 7-year period, 32 patients with Pseudomonas aeruginosa infection were identified on an HIV treatment service at a university-affiliated teaching hospital. The number of cases increased from 2 in 1986 to 13 in 1992. Affected patients had evidence of advanced HIV infection. In those treated with antiretroviral therapy, 96% of infections occurred > 1 year after initial presentation with HIV disease. Eighteen cases of pneumonia and 14 nonpulmonary (central venous access device, soft tissue, middle ear-mastoid, corneal, and peritoneal) infections were seen. Comparison with matched controls identified use of a central venous access device and administration of aerosolized pentamidine, corticosteroids, or ganciclovir as risk factors for infection (odds ratios, 5.3, 6.5, 15.0, and 9.0, respectively; p = 0.004, 0.007, 0.02, and 0.02, respectively). Seventy-five percent of cases had community onset, but time since last hospital discharge was significantly shorter in study patients than in controls (mean difference, -85 days; 95% confidence interval, -24 to -146; p = 0.01). Among evaluable cases, outcome was fatal (survival < or = 30 days) in 2 of 16 (13%) patients in whom initial antibiotic therapy was appropriate and 8 of 14 (57%) patients in whom initial therapy was not appropriate (p = 0.016). Ten recurrent infections were seen in 8 of 21 patients who survived the initial infection. Median survival after onset of infection was only 80 days. Pseudomonas aeruginosa infection is an increasingly frequent, severe complication of advanced HIV disease. Several treatment and prevention strategies used in the management of advanced HIV disease are associated with an increased risk of infection.