Study of Once Daily Elvucitabine Versus Lamivudine in Participants With a Documented M184V Mutation
Study Details
- Human Immunodeficiency Virus
- Drug: Elvucitabine
- Drug: Lamivudine
- Clinically stable HIV-1 infected participants
- Ages \>18 and \<65 years
- Documented M184V mutation
- CD4 cell count \>100 cells/mL
- Plasma HIV-1 RNA levels \>5000 and \<150,000 copies/milliliter (mL)
- Currently receiving lamivudine or emtricitabine
- Other hematologic and metabolic parameters must be met.
- Provide written informed consent
- Other inclusion criteria apply.
- Hepatitis B antigen positive
- HIV-1 genotype positive for more than or equal to 4 protease mutations
- HIV-1 genotype positive for more than or equal to 2 non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations
- Previous therapy with cytotoxic or myelosuppressive drugs in the past 3 months
- Evidence or history of cirrhosis
- Women who are pregnant or breast feeding
- Other exclusion criteria apply.
Study Details
- Human Immunodeficiency Virus
- Drug: Elvucitabine
- Drug: Lamivudine
- Clinically stable HIV-1 infected participants
- Ages \>18 and \<65 years
- Documented M184V mutation
- CD4 cell count \>100 cells/mL
- Plasma HIV-1 RNA levels \>5000 and \<150,000 copies/milliliter (mL)
- Currently receiving lamivudine or emtricitabine
- Other hematologic and metabolic parameters must be met.
- Provide written informed consent
- Other inclusion criteria apply.
- Hepatitis B antigen positive
- HIV-1 genotype positive for more than or equal to 4 protease mutations
- HIV-1 genotype positive for more than or equal to 2 non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations
- Previous therapy with cytotoxic or myelosuppressive drugs in the past 3 months
- Evidence or history of cirrhosis
- Women who are pregnant or breast feeding
- Other exclusion criteria apply.
Protocol Summary
Human immunodeficiency virus (HIV)-1 infected participants receiving long-term therapy with lamivudine or emtricitabine (nucleoside reverse transcriptase inhibitors \[NRTIs\]) are at risk for the development of a mutation at position M184 on the HIV reverse transcriptase gene. This mutation confers resistance to both drugs (\>100 fold increase in the concentration of drug producing 50% inhibition \[IC50\]).
In-vitro studies with elvucitabine have shown that HIV-1 isolates with the M184V mutation show only a 10-fold increase in IC50 as compared to wild type HIV-1. Alexion Pharmaceuticals Inc. intention is to demonstrate that 10 milligrams (mg) of elvucitabine, administered once per day for 14 days with continued background anti-HIV-1 medications, will demonstrate a fall in HIV-1 ribonucleic acid (RNA) plasma levels, as compared to baseline. The data from this study will guide dosing in future long-term studies in HIV-1 infected participants with the M184V mutation.