Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy.

TitleIntracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy.
Publication TypeJournal Article
Year of Publication2007
AuthorsMoore JD, Acosta EP, Johnson VA, Bassett R, Eron JJ, Fischl MA, Long MC, Kuritzkes DR, Sommadossi J-P
JournalAntivir Ther
Date Published2007
KeywordsAnti-HIV Agents, Cytidine Triphosphate, Dideoxynucleotides, Drug Therapy, Combination, Female, HIV Infections, Humans, Lamivudine, Leukocytes, Mononuclear, Male, Reverse Transcriptase Inhibitors, Stavudine, Thymine Nucleotides, Zidovudine

BACKGROUND: Intracellular nucleoside reverse transcriptase inhibitor triphosphate (NRTI-TP) concentrations are crucial in suppressing HIV replication. Little is known about how commonly used dual-NRTI regimens affect the intracellular levels of NRTI-TPs, the active form of these drugs. This study investigates the effect of dual-NRTI therapy in intracellular NRTI-TP levels.

METHODS: NRTI and NRTI-TP concentrations were evaluated in HIV-infected patients receiving either lamivudine (3TC) and stavudine (d4T) or lamivudine with zidovudine (ZDV); NRTI and NRTI-TP concentrations were determined using a validated HPLC/MS/MS method. Plasma HIV-1 RNA levels were determined at baseline and monthly to examine the relationship between NRTI-TP concentrations and plasma HIV-1 RNA.

RESULTS: Forty-one subjects completed the study. 3TC-TP significantly increased between day 1 and week 28 from 1.48 to 5.00 pmol/10(6) peripheral blood mononuclear cells (PBMC; P < 0.0001). NRTI-TP concentrations for d4T and ZDV did not significantly increase, with values at week 28 of 0.011 and 0.02 pmol/10(6) PBMC, respectively. Mean NRTI-TP/plasma ratios were 3%, 0.007% and 0.05% for 3TC, d4T and ZDV, respectively. Linear relationships were observed between ZDV- and 3TC-TP and changes in plasma HIV-1 RNA.

CONCLUSION: Of the three drugs studied, only 3TC-TP levels increased significantly between day 1 and week 28. ZDV-TP and 3TC-TP levels were unaffected by dual-NRTI therapy relative to monotherapy, regardless of the combination (3TC-ZDV or 3TC-d4T). Intracellular levels of d4T-TP were similar to previous reports for dual-NRTI therapy; however, in the case of d4T, these values appear lower than those achieved with d4T monotherapy.

Alternate JournalAntivir. Ther. (Lond.)
PubMed ID17926654
Grant ListU01-AI38858 / AI / NIAID NIH HHS / United States