Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy

被引：363

作者：

Dinoso, J. B. ^{[2
,3
]}

Kim, S. Y. ^{[2
]}

Wiegand, A. M. ^{[1
]}

Palmer, S. E. ^{[1
]}

Gange, S. J. ^{[4
]}

Cranmer, L. ^{[2
]}

O'Shea, A. ^{[5
]}

Callender, M. ^{[2
]}

Spivak, A. ^{[2
]}

Brennan, T. ^{[2
]}

Kearney, M. F. ^{[1
]}

Proschan, M. A. ^{[6
]}

Mican, J. M. ^{[7
]}

Rehm, C. A. ^{[7
]}

Coffin, J. M. ^{[1
,8
]}

Mellors, J. W. ^{[9
]}

Siliciano, R. F. ^{[2
,10
]}

Maldarelli, F. ^{[1
]}

机构：

[1] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA

[5] NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA

[6] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA

[7] NIAID, Div Clin Res, Bethesda, MD 20892 USA

[8] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA

[9] Univ Pittsburgh, Sch Med, Dept Infect Dis, Pittsburgh, PA 15261 USA

[10] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 23期

关键词：

antiretroviral drug intensification; HIV-1; persistance; viral reservoir; HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; CD4(+) T-CELLS; RECEIVING COMBINATION THERAPY; CEREBROSPINAL-FLUID; LATENT RESERVOIR; HIV-1-INFECTED PATIENTS; DRUG CONCENTRATIONS; LIFELONG PERSISTENCE; VIROLOGICAL OUTCOMES;

D O I：

10.1073/pnas.0903107106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

引用

页码：9403 / 9408

页数：6

共 54 条

[1] [Anonymous], 2008, Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Management
[2] Failure to detect nelfinavir in the cerebrospinal fluid of HIV-1-infected patients with and without AIDS dementia complex
Aweeka, F
Jayewardene, A
Staprans, S
Bellibas, SE
Kearney, B
Lizak, P
Novakovic-Agopian, T
Price, RW
[J]. JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY, 1999, 20 (01): : 39 - 43
[3] Residual human immunodeficiency virus type 1 viremia in some patients on Antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells
Bailey, JR
Sedaghat, AR
Kieffer, T
Brennan, T
Lee, PK
Wind-Rotolo, M
Haggerty, CM
Kamireddi, AR
Liu, Y
Lee, J
Persaud, D
Gallant, JE
Cofrancesco, J
Quinn, TC
Wilke, CO
Ray, SC
Siliciano, JD
Nettles, RE
Siliciano, RF
[J]. JOURNAL OF VIROLOGY, 2006, 80 (13) : 6441 - 6457
[4] Low atazanavir concentrations in cerebrospinal fluid
Best, Brookie M.
Letendre, Scott L.
Brigid, Eileen
Clifford, David B.
Collier, Ann C.
Gelman, Benjamin B.
McArthur, Justin C.
McCutchan, J. Allen
Simpson, David M.
Ellis, Ronald
Capparelli, Edmund V.
Grant, Igor
[J]. AIDS, 2009, 23 (01) : 83 - 87
[5] IN-VIVO FATE OF HIV-1-INFECTED T-CELLS - QUANTITATIVE-ANALYSIS OF THE TRANSITION TO STABLE LATENCY
CHUN, TW
FINZI, D
MARGOLICK, J
CHADWICK, K
SCHWARTZ, D
SILICIANO, RF
[J]. NATURE MEDICINE, 1995, 1 (12) : 1284 - 1290
[6] Quantification of latent tissue reservoirs and total body viral load in HIV-1 Infection
Chun, TW
Carruth, L
Finzi, D
Shen, XF
DiGiuseppe, JA
Taylor, H
Hermankova, M
Chadwick, K
Margolick, J
Quinn, TC
Kuo, YH
Brookmeyer, R
Zeiger, MA
BarditchCrovo, P
Siliciano, RF
[J]. NATURE, 1997, 387 (6629) : 183 - 188
[7] Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy
Chun, TW
Stuyver, L
Mizell, SB
Ehler, LA
Mican, JAM
Baseler, M
Lloyd, AL
Nowak, MA
Fauci, AS
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (24) : 13193 - 13197
[8] The central nervous system is a viral reservoir in simian immunodeficiency virus-infected macaques on combined antiretroviral therapy: A model for human immunodeficiency virus patients on highly active antiretroviral therapy
Clements, JE
Li, M
Gama, L
Bullock, B
Carruth, LM
Mankowski, JL
Zink, MC
[J]. JOURNAL OF NEUROVIROLOGY, 2005, 11 (02) : 180 - 189
[9] Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens
Colonno, R
Rose, R
McLaren, C
Thiry, A
Parkin, N
Friborg, J
[J]. JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (10) : 1802 - 1810
[10] Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy
Dornadula, G
Zhang, H
VanUitert, B
Stern, J
Livornese, L
Ingerman, MJ
Witek, J
Kedanis, RJ
Natkin, J
DeSimone, J
Pomerantz, RJ
[J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1999, 282 (17): : 1627 - 1632

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