The ALBI trial: a randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with human immunodeficiency virus.

A total of 151 previously untreated patients infected with human immunodeficiency virus type 1 (HIV-1) with CD4 cell counts >/=200/microL and plasma HIV-1 RNA levels of 10,000-100,000 copies/mL were randomly assigned to 24 weeks of open-labeled stavudine plus didanosine (group 1), zidovudine plus lamivudine (group 2), or stavudine plus didanosine followed by zidovudine plus lamivudine (group 3). The mean decrease in HIV-1 RNA level was greater in group 1 (2.26 log10 copies/mL) than in groups 2 (1.26 log10 copies/mL) or 3 (1.58 log10 copies/mL; P<.0001). The mean increase in CD4 cell counts was greater in groups 1 (124 cells/microL) and 3 (118 cells/microL) than in group 2 (62 cells/microL; P=.02). All regimens were generally well tolerated. The combination of stavudine plus didanosine reduced plasma HIV-1 RNA concentrations and increased CD4 cell counts more effectively than did the combination of zidovudine plus lamivudine or the regimen alternating both combinations.

Results of the ALBI trial: a randomized comparison of stavudine/didanosine, zidovudine/lamivudine and alternating treatment in antiretroviral-naive patients.

In the ALBI trial, 151 antiretroviral-naive patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 10,000 to 100,000 copies/ml and CD4 cell counts > or = 200 cells/mm3 received 24 weeks of treatment with stavudine/didanosine (n=51), zidovudine/lamivudine (n=51) or stavudine/didanosine for 12 weeks followed by zidovudine/lamivudine (n=49). Baseline plasma HIV-1 RNA and CD4 cell counts were comparable in the treatment groups. The mean decrease in plasma HIV-1 RNA at 24 weeks in the stavudine/didanosine group (2.26 log10) was significantly greater than that in either the zidovudine/lamivudine group (1.26 log10) or the alternating treatment group (1.58 log10) (P<0.0001 for both). Proportions of patients with plasma HIV-1 RNA level <500 copies/ml (91% vs 42% and 60%) and <50 copies/ml (47% versus 4% and 9%) were significantly greater in the stavudine/didanosine group (P<0.001 for pairwise comparisons). Stavudine/didanosine was associated with a mean increase in CD4 cell count (124 cells/mm3) significantly greater than that in the zidovudine/lamivudine group (62 cells/mm3, P<0.01) and comparable to that in the alternating group (118 cells/mm3). All study regimens were well tolerated. These findings, indicating superiority of stavudine/didanosine over zidovudine/lamivudine in virological and immunological response over 24 weeks, suggest that the combination should be considered as a basis for highly active antiretroviral therapy.

Risk factors for intestinal microsporidiosis in patients with human immunodeficiency virus infection: a case-control study.

A prospective unmatched case-control study was conducted to determine risk factors for intestinal microsporidiosis in persons infected with human immunodeficiency virus (HIV) who had < or = 200 CD4 cells/mm3. In multivariate analysis, case-patients (n = 30) were more likely than were control-subjects (n = 56) to have < or = 100 CD4 cells/mm3 (odds ratio [OR], 6.5; 95% confidence interval [CI], 1-42), to report male homosexual preference (OR, 7.6; 95% CI, 1-59.5), and to report swimming in a pool in the previous 12 months (OR, 9.2; 95% CI, 2.1-38.9). In summary, intestinal microsporidiosis in persons with HIV infection and < or = 200/mm3 CD4 cells is associated with male homosexuality and swimming in pools, suggesting fecal-oral transmission, including sexual and waterborne routes.

Gene transfer to human fetal pulmonary tissue developed in immunodeficient SCID mice.

Human fetal lung rudiments (8-12 weeks of development) undergo considerable growth upon microsurgical ectopic implantation in the xenograft-tolerant SCID mouse, and differentiate into a lung-like tissue that includes: (i) bronchial structures lined with pseudostratified, secretory, ciliated epithelium surrounded by smooth muscle and cartilage rings, (ii) submucosal glands, and (iii) alveolar sacs. Normal expression of the cystic fibrosis transmembrane conductance regulator (CFTR) protein was detected by immunostaining in those grafts, and similar differentiation was observed from either normal or cystic fibrosis (CF) fetal lung rudiments. Upon microinjection into human CF or normal lung grafts in SCID mice, beta-galactosidase-adenovirus gene constructs were efficiently transduced into epithelial and glandular cells. Such an in vivo replica of the human respiratory tissue may be a useful experimental model to study normal and pathologic lung development, and to assay candidate therapeutic gene constructs preclinically.