Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral
Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral
复制标题
在使用持久抑制性高活性抗逆转录病毒药物治疗临床无法检测到病毒载量的患者中，重组 HIV-1 痘病毒免疫期间残留病毒血症中持续的人类免疫缺陷病毒 1 型 (HIV-1) 复制的鉴定
DOI：
10.1128/jvi.00570-09
复制
发表时间：
2009
影响因子：
5.4
通讯作者：
PediatricAIDSC
中科院分区：
文献类型：
--
作者：
Shiu,Carlum;Cunningham,ColeenK;Greenough,Thomas;Muresan,Petronella;Sanchez-Merino,Victor;Carey,Vincent;Jackson,JBrooks;Ziemniak,Carrie;Fox,Lawrence;Belzer,Marvin;Ray,StuartC;Luzuriaga,Katherine;Persaud,Deborah;PediatricAIDSC
In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of <50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production from HIV-1 reservoirs to persistent low-level viremia during HAART remain controversial. HIV-1 vaccination of HAART-treated individuals provides a model for examining low-level viremia, as immunizations may facilitate virus replication and sequence evolution. In a phase 1 trial of modified vaccinia virus Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults receiving HAART, we assessed the prevalence of low-level viremia and sequence evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five-copy sensitivity) assays. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was significantly correlated with levels of viremia of between 6.5 and <50 copies/ml (P= 0.03) and was more likely to occur within epitopes presented by relevant HLA alleles (P< 0.001). These findings suggest that ongoing virus replication contributes to low-level viremia in patients on HAART and that this ongoing replication is subject to CD8+T-cell selective pressures.
