Comparative assessment of antiretrovirals in human monocyte-macrophages and lymphoid cell lines acutely and chronically infected with the human immunodeficiency virus.
We compared the efficacy of 3 antiretrovirals in cultured human peripheral blood monocyte-derived macrophages and lymphoid cells infected with the human immunodeficiency virus (HIV). Zidovudine (greater than 0.01 micrograms/ml) or foscarnet (greater than or equal to 100 micrograms/ml) consistently inhibited HIV replication (p24 antigen production) in acutely infected macrophages by more than 90%; alpha interferon (1,000 units/ml) inhibited HIV replication by 88-99%. Drug efficacy was equal in lymphoid cells and monocyte-derived macrophages. However, these antiretrovirals even in high concentration only minimally inhibited chronic, established HIV infection: while zidovudine (0.01 micrograms/ml) inhibited infection by over 90% in acutely infected macrophages and lymphoid cells, 50 micrograms/ml of this antiretroviral produced only 19-55% inhibition of HIV replication in chronically infected cells. Slot-blot analysis of HIV RNA was concordant with the p24 antigen data. Acutely infected macrophages are as susceptible to the inhibitory effects of antiretrovirals as lymphoid cells; however, chronically infected macrophages (which probably constitute the main in vivo reservoir for HIV) are several orders of magnitude more resistant.
Crowe
S M
SM
MacFarlane Burnet Centre for Medical Research, Fairfield Hospital, Melbourne, Australia.
McGrath
M S
MS
Elbeik
T
T
Kirihara
J
J
Mills
J
J
D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017245:Foscarnet; D015683:Gene Products, gag / Q000096:biosynthesis; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015488:HIV Antigens; D016655:HIV Core Protein p24; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D009000:Monocytes / Q000187:drug effects* / Q000382:microbiology; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D012367:RNA, Viral / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology
D000998:Antiviral Agents; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D007370:Interferon Type I; D012367:RNA, Viral; D014758:Viral Core Proteins; D017245:Foscarnet; D015215:Zidovudine; D010746:Phosphonoacetic Acid