Efficacy and safety of didanosine and lamivudine both once daily plus indinavir in human immunodeficiency virus-infected patients.

Abstract

Background: The combination of didanosine (DDI) and lamivudine (3TC) has been not recommended in guidelines for the first-line treatment of human immunodeficiency virus (HIV) infection because two major considerations might reduce its efficacy. First, both drugs are non-thymidine nucleosides and might exert less antiviral activity on activated T cells. Second, the codon 184 mutation emerging under 3TC failure could confer cross-resistance to DDI. However, because the intracellular half-life of their active metabolites allows administration once daily, the resulting improvement in patient compliance should favor this combination over others.

Patients and methods: We analyzed the virologic and immunologic outcome at 6 months in 46 naive HIV-infected patients (41% were intravenous drug users) who began a treatment of a triple combination of DDI, 3TC, and indinavir (IDV) with the schedule optimized to improve adherence. Both DDI and 3TC were administered once daily (450 mg and 300 mg, respectively) and IDV was taken twice daily (1,200 mg). Patients chose schedules at their convenience, according to their job timings and preferences. All had a plasma viral load (PVL) of more than 500 HIV-RNA copies/mL at the time they entered the study, and overall the mean PVL value was 54,201 copies/mL.

Results: Overall, nine patients did not complete the study period: two died of non-acquired immunodeficiency syndrome (AIDS)-related causes, three described severe gastrointestinal symptoms, one discontinued therapy voluntarily, and three were lost to follow-up. Among the remaining 37 patients, a PVL value of less than 500 copies/mL was reached by 31 (83.7%) patients, and values below 40 copies/mL were recorded in 71% (22/31) of them. Overall, a clinically significant increase in the CD4 cell count (more than 60 cells/microL) was seen in 70.2% (26/37) of patients. Treatment adherence, assessed using both self-reporting and the pill count method, was considered good (more than 90% of pills prescribed were taken) in all but four patients; three of them were among those six who did not reach undetectable PVL values at the sixth month. Mutations at codons 184, 74, 65, and 151, which confer resistance to 3TC and DDI, could be examined in 12 of the 15 patients having PVL values above 40 copies/mL at the sixth month. The codon 184 mutation emerged in 25%, meanwhile the codon 74 mutation only appeared in one patient; none carried the codon 151 mutant genotype. Nine months after beginning treatment, 29 (93.5%) of the 31 patients who reached less than 500 copies/mL at the sixth month still sustained PVL values below this threshold, and 25 (80.6%) had less than 40 copies/mL.

Conclusion: The combination of DDI and 3TC both once daily plus IDV twice daily is well tolerated, seems to favor a good adherence, and shows significant antiviral activity.