Viral replication under combination antiretroviral therapy: A comparison of four different regimens

A mathematical model of the interaction among CD4⁺ T-cells, HIV-1, and antiretroviral drugs was fitted to the viral load decline following initiation of combination therapy to estimate differences in the residual reproductive capacity of virus (R₀) in the average patient in each group. Four regimens were studied: 12 patients on 5-drug nucleoside reverse transcriptase inhibitor (NRTIs), nonnucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitor (PI)-containing combination therapy, 11 patients on PI-containing triple therapy, 10 patients on double NRTI therapy, and 10 patients on NNRTI- containing triple therapy. Model fits were used to estimate R₀. The NNRTI-containing triple therapy and the 5-drug regimen blocked viral replication to the greatest extent (R₀ = 0.85; 95% confidence interval [CI], 0.79-0.91; and 0.90, 95% CI, 0.82-0.98, respectively), with the former being significantly better than the PI-containing triple regimen (R₀ = 0.98; 95% CI, 0.92-1.03; p = .007). Both the NNRTI-containing and the 5-drug regimen, as well as the PIcontaining triple therapy, were significantly better at blocking viral replication than the double NRTI therapy (R_O = 1.04; 95% CI, 1.0-1.07). Measurement of viral load after approximately 7 days provided the most accurate measure of the degree of viral suppression induced by a given drug regimen.