SEQUENTIAL VERSUS SIMULTANEOUS COMBINATION ANTIRETROVIRAL REGIMENS FOR THE TREATMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN-VITRO

Two-, three-, and four-drug antiretroviral combinations in either simu ltaneous or sequential regimens were evaluated for their ability to su ppress human immunodeficiency virus (HIV) type 1 replication in vitro. Zidovudine, lamivudine, saquinavir, and nevirapine were used at IC(90 )s, IC(99)s, or IC(greater than or equal to 99)s in a CD4-positive hum an lymphoblastoid cell line (H9 cells) acutely infected with HIV-1. In sequential regimens, drugs were added at weekly intervals. In simulta neous regimens, all drugs were added on day 0. Increasing the number o f drugs in a combination regimen both increased the degree of viral in hibition and delayed the time of breakthrough viral replication. Simul taneous regimens provided more profound and earlier viral inhibition t han did sequential regimens. However, sequential addition provided rel atively more durable viral inhibition than did simultaneous regimens w hen drug concentrations were low. The relative effectiveness of differ ent HIV-1 therapeutic strategies depends on both the numbers and conce ntrations of the drugs used.