AEGiS-15IAC: In vitro anti-HIV-1 combination studies of tenofovir with abacavir and lamivudine in primary cells.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

In vitro anti-HIV-1 combination studies of tenofovir with abacavir and lamivudine in primary cells.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1237)

Miller MD, Myrick F, Borroto-Esoda K
Gilead Sciences, Durham, NC, United States

BACKGROUND: Antiretroviral therapy with the triple nucleoside combination of abacavir (ABC), tenofovir DF, and lamivudine (3TC) dosed once-daily has resulted in poor treatment outcomes. The basis for the poor outcomes of this regimen is unclear. Previous in vitro analyses in immortalized cell lines using 2-drug combinations have demonstrated no antiviral antagonism between any of these drugs. OBJECTIVE: To study potential 2- and 3-drug interactions among tenofovir, ABC and 3TC in primary peripheral blood mononuclear cells (PBMCs) infected with HIV-1.

METHODS: Activated healthy donor PBMCs were infected with wild-type HIV-1 (HXB2) in the presence of each 2-drug combination of tenofovir (TFV), ABC and 3TC using concentrations of drugs that span the IC50 values. In addition, 3 fixed concentrations of 3TC (25 nM, 50 nM and 150 nM) were added onto TFV-ABC combinations. After 4 days, the antiviral effect of each drug combination was determined by measuring HIV-1 p24 antigen production. 3-5 replicates of each drug combination were averaged together. The data were analyzed with the MacSynergy II program and by isobologram analysis.

RESULTS: Using both analytical methods, the 2-drug combination of TFV-3TC showed slightly synergistic anti-HIV activity. The two drug combination of ABC-3TC showed additive to slightly synergistic activity and the TFV-ABC combination displayed additive anti-HIV activity. Addition of 3TC in three fixed doses to the TFV-ABC combination maintained the same additive anti-HIV activity as observed for TFV-ABC in the absence of 3TC. There was no antiviral antagonism observed for any of the 2- or 3-drug combinations in these primary cells.

CONCLUSIONS: The combination of tenofovir, abacavir and lamivudine showed additive anti-HIV activity in primary PBMCs. There was no evidence for antiviral antagonism among tenofovir, abacavir or lamivudine.

Keywords: AEGIS, Dideoxynucleosides, Lamivudine, HIV-1, Adenine, Organophosphorus Compounds, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Acquired Immunodeficiency Syndrome, HIV-1 Reverse Transcriptase, HIV, HIV Infections, HIV Seropositivity, Antiviral Agents, Drug Combinations, abacavir, tenofovir, In Vitro

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WeOrB1237