Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial

Hiroyu Hatano; Matthew C. Strain; Rebecca Scherzer; Peter Bacchetti; Deborah Wentworth; Rebecca Hoh; Jeffrey N. Martin; Joseph M. Mccune; James D. Neaton; Russell P. Tracy; Priscilla Y. Hsue; Douglas D. Richman; Steven G. Deeks

doi:10.1093/infdis/jit453

Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial

Hiroyu Hatano, Matthew C. Strain, Rebecca Scherzer, Peter Bacchetti, Deborah Wentworth, Rebecca Hoh, Jeffrey N. Martin, Joseph M. Mccune, James D. Neaton, Russell P. Tracy, Priscilla Y. Hsue, Douglas D. Richman, Steven G. Deeks

Biostatistics

Research output: Contribution to journal › Article › peer-review

147 Scopus citations

Abstract

Background. The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles.Methods. Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4⁺ T-cell count of ≥350 cells/mm³ for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8.Results. The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P =. 0025) and the week 2 to 0 ratio was 5.7-fold higher (P =. 023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P =. 045).Conclusions. Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection.

Original language	English (US)
Pages (from-to)	1436-1442
Number of pages	7
Journal	Journal of Infectious Diseases
Volume	208
Issue number	9
DOIs	https://doi.org/10.1093/infdis/jit453
State	Published - Nov 1 2013

Bibliographical note

Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (grants R01 AI087145, K24 AI069994, AI080193, AI69432, AI047745, and AI74621); the Delaney AIDS Research Enterprise (grant U19 AI0961090); the Collaboratory for AIDS Research on Eradication (grant U19 AI096113); the National Heart Lung and Blood Institute (grant R01 HL095130); the American Foundation for AIDS Research (grant 106710–40-RGRL); the UCSF/Gladstone Institute of Virology & Immunology Center for AIDS Research (CFAR; grant P30 AI027763); the University of California, San Diego, CFAR (grant AI306214); the University of California, San Francisco, Clinical and Translational Research Institute Clinical Research Center (grant UL1 RR024131); the Center for AIDS Prevention Studies (grant P30 MH62246); the CFAR Network of Integrated Systems (grant R24 AI067039); and the Department of Veterans Affairs.

Keywords

2-LTR circles
D-dimer
HIV
ongoing viral replication
raltegravir intensification

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hatano, H., Strain, M. C., Scherzer, R., Bacchetti, P., Wentworth, D., Hoh, R., Martin, J. N., Mccune, J. M., Neaton, J. D., Tracy, R. P., Hsue, P. Y., Richman, D. D., & Deeks, S. G. (2013). Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial. Journal of Infectious Diseases, 208(9), 1436-1442. https://doi.org/10.1093/infdis/jit453

Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial. / Hatano, Hiroyu; Strain, Matthew C.; Scherzer, Rebecca et al.
In: Journal of Infectious Diseases, Vol. 208, No. 9, 01.11.2013, p. 1436-1442.

Research output: Contribution to journal › Article › peer-review

Hatano, H, Strain, MC, Scherzer, R, Bacchetti, P, Wentworth, D, Hoh, R, Martin, JN, Mccune, JM, Neaton, JD, Tracy, RP, Hsue, PY, Richman, DD & Deeks, SG 2013, 'Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial', Journal of Infectious Diseases, vol. 208, no. 9, pp. 1436-1442. https://doi.org/10.1093/infdis/jit453

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title = "Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial",

abstract = "Background. The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles.Methods. Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4+ T-cell count of ≥350 cells/mm3 for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8.Results. The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P =. 0025) and the week 2 to 0 ratio was 5.7-fold higher (P =. 023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P =. 045).Conclusions. Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection.",

keywords = "2-LTR circles, D-dimer, HIV, ongoing viral replication, raltegravir intensification",

author = "Hiroyu Hatano and Strain, {Matthew C.} and Rebecca Scherzer and Peter Bacchetti and Deborah Wentworth and Rebecca Hoh and Martin, {Jeffrey N.} and Mccune, {Joseph M.} and Neaton, {James D.} and Tracy, {Russell P.} and Hsue, {Priscilla Y.} and Richman, {Douglas D.} and Deeks, {Steven G.}",

note = "Funding Information: Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (grants R01 AI087145, K24 AI069994, AI080193, AI69432, AI047745, and AI74621); the Delaney AIDS Research Enterprise (grant U19 AI0961090); the Collaboratory for AIDS Research on Eradication (grant U19 AI096113); the National Heart Lung and Blood Institute (grant R01 HL095130); the American Foundation for AIDS Research (grant 106710–40-RGRL); the UCSF/Gladstone Institute of Virology & Immunology Center for AIDS Research (CFAR; grant P30 AI027763); the University of California, San Diego, CFAR (grant AI306214); the University of California, San Francisco, Clinical and Translational Research Institute Clinical Research Center (grant UL1 RR024131); the Center for AIDS Prevention Studies (grant P30 MH62246); the CFAR Network of Integrated Systems (grant R24 AI067039); and the Department of Veterans Affairs.",

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doi = "10.1093/infdis/jit453",

language = "English (US)",

volume = "208",

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journal = "Journal of Infectious Diseases",

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TY - JOUR

T1 - Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection

T2 - A randomized, placebo-controlled trial

AU - Hatano, Hiroyu

AU - Strain, Matthew C.

AU - Scherzer, Rebecca

AU - Bacchetti, Peter

AU - Wentworth, Deborah

AU - Hoh, Rebecca

AU - Martin, Jeffrey N.

AU - Mccune, Joseph M.

AU - Neaton, James D.

AU - Tracy, Russell P.

AU - Hsue, Priscilla Y.

AU - Richman, Douglas D.

AU - Deeks, Steven G.

N1 - Funding Information: Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (grants R01 AI087145, K24 AI069994, AI080193, AI69432, AI047745, and AI74621); the Delaney AIDS Research Enterprise (grant U19 AI0961090); the Collaboratory for AIDS Research on Eradication (grant U19 AI096113); the National Heart Lung and Blood Institute (grant R01 HL095130); the American Foundation for AIDS Research (grant 106710–40-RGRL); the UCSF/Gladstone Institute of Virology & Immunology Center for AIDS Research (CFAR; grant P30 AI027763); the University of California, San Diego, CFAR (grant AI306214); the University of California, San Francisco, Clinical and Translational Research Institute Clinical Research Center (grant UL1 RR024131); the Center for AIDS Prevention Studies (grant P30 MH62246); the CFAR Network of Integrated Systems (grant R24 AI067039); and the Department of Veterans Affairs.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Background. The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles.Methods. Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4+ T-cell count of ≥350 cells/mm3 for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8.Results. The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P =. 0025) and the week 2 to 0 ratio was 5.7-fold higher (P =. 023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P =. 045).Conclusions. Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection.

AB - Background. The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles.Methods. Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4+ T-cell count of ≥350 cells/mm3 for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8.Results. The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P =. 0025) and the week 2 to 0 ratio was 5.7-fold higher (P =. 023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P =. 045).Conclusions. Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection.

KW - 2-LTR circles

KW - D-dimer

KW - HIV

KW - ongoing viral replication

KW - raltegravir intensification

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Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV Infection: A randomized, placebo-controlled trial

Abstract

Bibliographical note

Keywords

UN SDGs

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