Modest Nonadherence to Antiretroviral Therapy Promotes Residual HIV-1 Replication in the Absence of Virological Rebound in Plasma

被引:77
作者
Pasternak, Alexander O. [1 ,3 ]
de Bruin, Marijn [5 ]
Jurriaans, Suzanne [2 ]
Bakker, Margreet [1 ,3 ]
Berkhout, Ben [1 ,3 ]
Prins, Jan M. [4 ]
Lukashov, Vladimir V. [1 ,3 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Lab Expt Virol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Lab Clin Virol, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, NL-1105 AZ Amsterdam, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands
[5] Wageningen Univ, Dept Commun Sci, Wageningen, Netherlands
关键词
PROTEASE INHIBITOR THERAPY; HIGHLY SENSITIVE METHODS; T-CELL-ACTIVATION; INFECTED INDIVIDUALS; VIRAL SUPPRESSION; IMMUNE ACTIVATION; DRUG-RESISTANCE; VIREMIA BLIPS; ADHERENCE; RNA;
D O I
10.1093/infdis/jis502
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Modern antiretroviral therapy (ART) regimens are widely assumed to forgive modest nonadherence, because virological suppression in plasma is common at adherence levels of >70%. Yet, it is unknown whether human immunodeficiency virus type 1 (HIV-1) replication is completely suppressed at these levels of adherence. Methods. We longitudinally quantified levels of cell-associated HIV-1 RNA and DNA in 40 patients (median duration of successful ART before study initiation, 46 months), whose 1-week adherence to therapy prior to the sampling moments was measured electronically. Results. Patients were constantly 100% adherent (the optimal-adherence group), demonstrated improving adherence over time (the improving-adherence group), or neither of the above (the poor-adherence group). Adherence never decreased to <70% in any patient, and no rebound in plasma virological levels was observed. Nevertheless, poor adherence but not optimal or improving adherence caused a significant longitudinal increase in cell-associated HIV RNA levels (P = .006). Time-weighted changes and regression slopes of viral RNA load for the poor-adherence group were significantly higher than those for the optimal-adherence group (P < .01). Conclusions. Because ART only blocks infection of new cells but not viral RNA transcription in cells infected before therapy initiation, the observed effects strongly suggest that modest nonadherence can cause new cycles of HIV-1 replication that are undetectable by commercial plasma viral load assays.
引用
收藏
页码:1443 / 1452
页数:10
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