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Background: Ongoing HIV-1 replication during HAART remains a major obstacle in our therapeutic effort. We examined whether a new 4-drug combination might be more potent than common regimens by comparing the initial decay rate of plasma viremia after therapy.
Methods: Nineteen patients have been treated with lopinavir/ritonavir, efavirenz, tenofovir, and lamivudine for a mean of 45 days (range 7—70). Their results were compared to those obtained from 26 cases treated with saquinavir, ritonavir, zidovudine, and lamivudine and 11 cases treated with nelfinavir, zidovudine, and lamivudine. All patients were either drug-naïve or had drug-sensitive HIV-1, and the baseline viral loads and CD4 levels were comparable in the 3 groups.
Results: Frequent measurements showed that viral loads did not decrease for the first 1—2 days of the new regimen, but dropped sharply thereafter. The first phase of viral decay ended by day 4 to 7, which is much earlier than what has been observed with standard HAART. The mean log change in viral load from day 0 to day 7 was 1.59+0.12, compared to 1.14+0.10 for the other 4-drug regimen and 1.32+0.13 for the 3-drug regimen. Correspondingly, the decay slope for this phase was -0.57+0.06/d, compared to -0.41+0.03/d and -0.45+0.04/ d. The differences in mean change in viral load became insignificant by week-4. Previous viral dynamics studies have shown that the first rapid phase of viral decay is a reflection of the product of two parameters: life span of the productively infected CD4 lymphocytes and potency of the antiviral regimen.
Conclusion: Thus, assuming that the life span of infected cells is the same in these three comparable groups of patients, the relative potency of the regimens could be determined based on the slopes of the initial viral decline. Assigning our new 4-drug regimen an arbitrary potency of 1.0, the other four- and three-drug combinations have relative potencies of 0.72 and 0.78, respectively. Our results indicate that antiretroviral regimens in common use today may be significantly less potent than previously believed.
Authors
1Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ.;2Abbott Labs;3Gilead Pharmaceuticals; and4DuPont Pharmaceuticals.
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