HIV TRIALS

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Among various clinical endpoints currently used in the setting of HIV-1 infection, CD4 cell count represents the most extensively studied marker and has been shown to explain some, but not all, of the clinical effects of antiretroviral therapy, indicating that the ultimate effect of antiretroviral therapy could be due to, at least in part, factors not reflected in the effect of antiretroviral therapy on CD4 cell counts. In this regard, there are considerable amounts of data indicating that the viral load represents a major determinant of the severity of HIV- 1 related diseases and is related to the stage and progression of immunological deterioration. HIV-1 particle numbers determined by using the polymerase chain reaction (PCR) have been reported to reflect viremia status and viral load in individuals with HIV-1 infection and may serve as a potential clinical marker to monitor the disease process and effectiveness of antiretroviral therapy. In the present study, we examined changes in viremia levels and development of drug-related mutations in patients with symptomatic HIV-1 infection randomized to receive an alternating regimen (A-AZT/ddI) or simultaneous regimen (S-AZT/ddI) of AZT and ddI therapy. Both A-AZT/ddI and S-AZT/ddI arms had a significant reduction in serum RNA copy numbers during the first 2-3 months of therapy [8-fold (p=0.0002) and 31-fold (p=0.0005) lower than at entry for A-AZT/ddI and S-AZT/ddI, respectively] as assessed by PCR following reverse transcription of viral RNA extracted from serum. The reduction was greater in S-AZT/ddI arm than in A-AZT/ddI arm (p=O.0051 both at 2 week and 9 week). After 1 year, the viremia level remained significantly lower in both arms [13-fold (p=O.0005) for A- AZT/ddI; 9-fold (p=0.0024) forS-AZT/ddI], but there was no difference between the arms (p=O.37). The reduction was still present after 2 years [19-fold (p=0.039) for A-AZT/ddI; 8-fold lower (p=0.014) for S-AZT/ddI, respectively].