Abacavir expanded access program for adult patients infected with human immunodeficiency virus type 1.

Expanded access programs (EAPs) provide medication to patients with life-threatening, treatment-refractory illnesses before regulatory approval and allow the acquisition of safety information. A 2-part, multisite EAP to evaluate abacavir, a carbocyclic nucleoside reverse-transcriptase inhibitor for use in combination antiretroviral therapy, was conducted. The EAP involved >13,000 adults infected with human immunodeficiency virus type 1 (HIV-1) who no longer responded to commercially available treatment regimens. Part A (open-label trials) examined the efficacy, safety, and tolerance of abacavir, and part B (provision of abacavir through expanded access) assessed only the occurrence of serious adverse events. By month 2 of abacavir-containing treatment, plasma HIV-1 RNA levels decreased by > or =0.5 log(10) in 31.4% of patients, and 5.6% of the patients had HIV-1 RNA levels decrease to <400 copies/mL. Drug-related serious adverse events were reported by 7.7% of patients, the most common of which were nausea, skin rash, diarrhea, malaise or fatigue, and fever. Approximately 4.6% of patients experienced a hypersensitivity reaction that was possibly drug related. Overall, the types and incidences of adverse events reported in the abacavir EAP were similar to those reported in phase 2 and 3 clinical trials evaluating abacavir.

Lamivudine 300 mg QD versus continued lamivudine 150 mg BID with stavudine and a protease inhibitor in suppressed patients.

PURPOSE: To compare the efficacy (sustained virologic suppression) and safety/tolerability of a switch to lamivudine 300 mg once daily (QD) versus continued lamivudine 150 mg twice daily (BID) in virologically suppressed patients (HIV-1 RNA <400 copies/mL for > or =3 months) on stable (> or =6 months) therapy with lamivudine 150 mg BID plus stavudine and either indinavir or nelfinavir. METHOD: Eighty-nine suppressed patients > or =18 years old with CD4 counts >50 cells/mm(3) were enrolled in this phase II, open-label, multicenter, randomized, stratified (by pretrial protease inhibitor [PI]), parallel-group clinical trial. Eighty-one patients received either lamivudine 300 mg QD (n = 39) or 150 mg BID (n = 42) with their pretrial stavudine/PI regimens for 24 weeks. RESULTS: A high rate of virologic suppression was sustained with both regimens throughout the trial. At week 24, intent-to-treat:exposed (missing = failure) analyses showed no statistically significant differences in the percentage of patients with HIV-1 RNA <400 copies/mL (95% [QD] vs. 90% [BID]) or <50 copies/mL (82% [QD] vs. 81% [BID]) or in the median change from baseline in CD4 counts (+42 cells/mm(3) [QD] vs. +22 cells/mm(3) [BID]). Both regimens were well tolerated. No patient experienced virologic failure, clinical disease progression, or a drug-related serious adverse event during the trial. Self-reported medication adherence was high in both groups. CONCLUSION: Patients who experience virologic suppression with a regimen of lamivudine 150 mg BID in combination with stavudine/PI can maintain that suppression by continuing their regimen or switching to lamivudine 300 mg QD and continuing the other components. Adverse event profiles were comparable among treatment regimens, and no new safety concerns were raised.

The NEAT study: a 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients.

OBJECTIVE: To compare the efficacy, durability, and tolerability of GW433908 (908), 1400 mg twice-daily (BID), with nelfinavir (NFV), 1250 mg BID. METHODS: This was an international, multicenter, randomized, open-label study (NEAT) in antiretroviral therapy (ART)-naive HIV-infected adults with plasma HIV-1 RNA (vRNA) at screening > or =5000 copies/mL (c/mL). Patients were randomly assigned to 908 or NFV (2:1) for a minimum of 48 weeks, with a background of abacavir (ABC) and lamivudine (3TC). RESULTS: A total of 166 patients received randomized treatment with 908 BID and 83 received NFV BID. The population was diverse with regard to race and gender (76% Hispanics and blacks, 31% female) and had advanced HIV disease at screening (45% had vRNA >100,000 c/mL, 48% had CD4 cell counts <200 cells/mm3, 20% had a history of Centers for Disease Control class C events). After 48 weeks of study by an intention-to-treat rebound or discontinuation = failure analysis, a greater proportion of patients in the 908 BID group (66%) than the NFV BID group (51%) achieved vRNA <400 c/mL. Furthermore, more patients with screening vRNA >100,000 c/mL (67 vs. 35%) or CD4 <50 cells/mm3 (48 vs. 24%) achieved undetectable viral loads taking 908 BID compared with NFV BID, respectively. Favorable immunologic responses were observed for both groups. Diarrhea, which was more common in the NFV BID group (18 vs. 5%), was the only drug-related grade 2-4 adverse event with a significant difference (P = 0.002) in incidence between groups. CONCLUSION: Administration of 908 BID resulted in a potent and sustained antiretroviral response, notably in ART-naive patients with advanced HIV disease. GW433908 was generally well tolerated and provides a convenient dosing option without food or fluid restrictions.