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 simultaneous or sequential regimens were evaluated for their ability to suppress human immunodeficiency virus (HIV) type 1 replication in vitro. Zidovudine, lamivudine, saquinavir, and nevirapine were used at IC90s, IC99s, or IC⩾99s i...

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Bibliographic Details
Published in:The Journal of infectious diseases 1997-08, Vol.176 (2), p.510-514
Main Authors: Oh, Myoung-don, Merrill, Debra P., Sutton, Lorraine, Hirsch, Martin S.
Format: Article
Language:English
Subjects:
AIDS/HIV
Anti-HIV Agents - administration & dosage
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antigens
Antiretrovirals
Antiviral agents
Antivirals
Biological and medical sciences
CD4-Positive T-Lymphocytes - virology
Cell Line
Concise Communications
Drug Administration Schedule
Experimental replication
HIV
HIV 1
HIV Core Protein p24 - biosynthesis
HIV-1 - drug effects
HIV-1 - physiology
Hospital units
Humans
Infections
Infectious diseases
Medical sciences
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Virus Replication - drug effects
Viruses
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Summary:Two-, three-, and four-drug antiretroviral combinations in either simultaneous or sequential regimens were evaluated for their ability to suppress human immunodeficiency virus (HIV) type 1 replication in vitro. Zidovudine, lamivudine, saquinavir, and nevirapine were used at IC90s, IC99s, or IC⩾99s in a CD4-positive human lymphoblastoid cell line (H9 cells) acutely infected with HIV-1. In sequential regimens, drugs were added at weekly intervals. In simultaneous regimens, all drugs were added on day 0. Increasing the number of drugs in a combination regimen both increased the degree of viral inhibition and delayed the time of breakthrough viral replication. Simultaneous regimens provided more profound and earlier viral inhibition than did sequential regimens. However, sequential addition provided relatively more durable viral inhibition than did simultaneous regimens when drug concentrations were low. The relative effectiveness of different HIV-1 therapeutic strategies depends on both the numbers and concentrations of the drugs used.
ISSN:0022-1899
1537-6613
DOI:10.1086/517277