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

Abstract

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.

Reverse Transcriptase Mutations in HIV-1 Infected Patients Treated with Two Nucleoside Analogues: The Smart Study

“…Roughly half of the responder patients had undetectable plasma viral load (pVL) at enrollment, which is consistent with previous reports (39,40). In our cohort, patients who reached undetectable pVL with two nucleoside analogues had a lower failure rate over one year compared to those who have a reduction of> 2 log 10, but still detectable, pVL.…”

Should Resistance Testing Be Performed for Treatment-Naive HIV-Infected Patients? A Cost-Effectiveness Analysis

“…On the basis of published literature, we estimated the likely virologic suppression rate of the first through fifth sequential line of therapy in patients with and patients without virus with genotypic resistance who were starting an efavirenz-based or a lopinavir/ritonavir-based initial regimen (table 2) [31][32][33][34][35][36][37][38]. Because limited data exist regarding efficacy of therapy with primary resistance, we estimated outcomes using studies of treatment-experienced patients and then varied the outcomes in sensitivity analyses.…”

“…For the tested population, the choice of initial regimen was based on the results of the genotype test. Efficacy of first-line therapy ranged from a high of 75% viral suppression at 48 weeks in patients with no PI or NRTI resistance who start receiving a lopinavir/ ritonavir-based initial regimen [34] to 19% viral suppression at 48 weeks in patients with baseline NNRTI resistance who start receiving an efavirenz-based initial regimen [33]. We assumed that patients without resistance could receive 5 sequential lines of treatment: 1 line of NNRTI-based treatment, 2 lines of PI-based treatment (with minimal PI resistance after the first treatment failure [42]), 1 line of enfuvirtide-based treatment, and a final salvage regimen without enfuvirtide.…”

Multiple Effects of the M184V Resistance Mutation in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1

“…However, with a DNA template, M184V RT showed higher fidelity than did the wildtype enzyme (34); this may potentially affect the development of resistance to other antiretroviral agents. In the ALBI trial (19), for example, the T215Y mutation developed in a significantly higher proportion of patients who were randomized to treatment with ddI-stavudine (ddI-d4T) (62%) than in those who were treated with ZDV-3TC (10%) (24). The Q151M multinucleoside resistance mutation was also observed less frequently in patients who had been treated with 3TC (24).…”