HIV-1 drug resistance profiles in children and adults with viral load of <50 copies/mL receiving combination therapy

被引:177
作者
Hermankova, M
Ray, SC
Ruff, C
Powell-Davis, M
Ingersoll, R
D'Aquila, RT
Quinn, TC
Siliciano, RF
Persaud, D
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Inst Genet, Baltimore, MD USA
[4] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
[5] Harvard Univ, Sch Med, Boston, MA USA
[6] NIAID, NIH, Bethesda, MD 20892 USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2001年 / 286卷 / 02期
关键词
D O I
10.1001/jama.286.2.196
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context The continued release of human immunodeficiency virus type 1 (HIV-1) into plasma at very low levels during highly active antiretroviral therapy (HAART) can be detected using specialized techniques, but the nature and significance of this low-level viremia, especially as related to acquisition of drug resistance mutations, are unclear. Objective To determine genetic resistance profiles of low-level plasma HIV-1 in patients with prolonged viral suppression (<50 copies/mL of plasma HIV-1 RNA) while receiving HAART. Design and Setting Cross-sectional study conducted at a US academic hospital from November 1999 to February 2001 using a novel method for amplification of low levels of viral genomes in plasma. Patients Eighteen HIV-1-infected patients (7 children and 11 adults), enrolled in a longitudinal study of HIV-1 reservoirs, who had suppression of viral replication while receiving protease inhibitor-containing combination therapy. Two patients (1 adult and 1 child) with less optimal suppression of viral replication were included to assess virus predominating when plasma HIV-1 RNA levels are low but detectable (<1000 copies/mL). Follow-up analyses were conducted in 3 patients. Main Outcome Measure Detection of drug resistance mutations in clones amplified from low-level plasma virus. Results Viral sequences were amplified from 8 of the 18 patients with simultaneous plasma HIV-1 measurements of less than 50 copies/mL and from 2 patients with 231 and 50 copies/mL. Clones from 3 treatment-naive patients with less than 50 copies/mL of plasma HIV-1 RNA showed continued release, for as long as 42 months, of wild-type drug-sensitive virus. The 7 patients with prior nonsuppressive therapy, with viral loads below 50 copies/mL and during "blips" to 231 and 64 copies/mL, had only resistance mutations consistent with pre-HAART therapy (although reverse transcriptase inhibitor mutations may have continued to occur), New HAART-related mutations were seen in a control patient with prior viral load levels of about 400 to 1000 copies/mL. For phylogenetic analysis, sequences were available for both resting CD4(+) T cells and plasma HIV for 7 of 10 patients and showed patient-specific clustering of sequences and a close relationship between virus in the plasma and the latent reservoir. Conclusions Based on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens, However, the archival drug-resistant virus may be relevant regarding future treatment strategies.
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收藏
页码:196 / 207
页数:12
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