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

Jeff D. Moore, Edward P. Acosta, Victoria A. Johnson, Roland Bassett, Joseph J. Eron, Margaret A Fischl, Mary C. Long, Daniel R. Kuritzkes, Jean Pierre Sommadossi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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/106 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.

Original languageEnglish
Pages (from-to)981-986
Number of pages6
JournalAntiviral Therapy
Volume12
Issue number6
StatePublished - Oct 3 2007

Fingerprint

Reverse Transcriptase Inhibitors
Lamivudine
Zidovudine
Nucleosides
HIV
HIV-1
RNA
Therapeutics
Stavudine
triphosphoric acid
Pharmaceutical Preparations
Blood Cells
High Pressure Liquid Chromatography
lamivudine triphosphate

ASJC Scopus subject areas

  • Pharmacology

Cite this

Moore, J. D., Acosta, E. P., Johnson, V. A., Bassett, R., Eron, J. J., Fischl, M. A., ... Sommadossi, J. P. (2007). Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy. Antiviral Therapy, 12(6), 981-986.

Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy. / Moore, Jeff D.; Acosta, Edward P.; Johnson, Victoria A.; Bassett, Roland; Eron, Joseph J.; Fischl, Margaret A; Long, Mary C.; Kuritzkes, Daniel R.; Sommadossi, Jean Pierre.

In: Antiviral Therapy, Vol. 12, No. 6, 03.10.2007, p. 981-986.

Research output: Contribution to journalArticle

Moore, JD, Acosta, EP, Johnson, VA, Bassett, R, Eron, JJ, Fischl, MA, Long, MC, Kuritzkes, DR & Sommadossi, JP 2007, 'Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy', Antiviral Therapy, vol. 12, no. 6, pp. 981-986.
Moore, Jeff D. ; Acosta, Edward P. ; Johnson, Victoria A. ; Bassett, Roland ; Eron, Joseph J. ; Fischl, Margaret A ; Long, Mary C. ; Kuritzkes, Daniel R. ; Sommadossi, Jean Pierre. / Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy. In: Antiviral Therapy. 2007 ; Vol. 12, No. 6. pp. 981-986.
@article{bddc60418a9a483e81de41f9764282c3,
title = "Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy",
abstract = "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/106 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.",
author = "Moore, {Jeff D.} and Acosta, {Edward P.} and Johnson, {Victoria A.} and Roland Bassett and Eron, {Joseph J.} and Fischl, {Margaret A} and Long, {Mary C.} and Kuritzkes, {Daniel R.} and Sommadossi, {Jean Pierre}",
year = "2007",
month = "10",
day = "3",
language = "English",
volume = "12",
pages = "981--986",
journal = "Antiviral Therapy",
issn = "1359-6535",
publisher = "International Medical Press Ltd",
number = "6",

}

TY - JOUR

T1 - Intracellular nucleoside triphosphate concentrations in HIV-infected patients on dual nucleoside reverse transcriptase inhibitor therapy

AU - Moore, Jeff D.

AU - Acosta, Edward P.

AU - Johnson, Victoria A.

AU - Bassett, Roland

AU - Eron, Joseph J.

AU - Fischl, Margaret A

AU - Long, Mary C.

AU - Kuritzkes, Daniel R.

AU - Sommadossi, Jean Pierre

PY - 2007/10/3

Y1 - 2007/10/3

N2 - 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/106 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.

AB - 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/106 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.

UR - http://www.scopus.com/inward/record.url?scp=34848886926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34848886926&partnerID=8YFLogxK

M3 - Article

C2 - 17926654

AN - SCOPUS:34848886926

VL - 12

SP - 981

EP - 986

JO - Antiviral Therapy

JF - Antiviral Therapy

SN - 1359-6535

IS - 6

ER -