Measuring covert HIV replication during HAART: the abundance of 2-LTR circles is not a reliable marker

F Bushman - Aids, 2003 - journals.lww.com
Aids, 2003journals.lww.com
The development of highly active anti-retroviral therapy (HAART) has conferred great
benefits to patients, but treatment failures are common. This leads to the question of what is
going on with the virus during the period of successful control. Is there ongoing 'covert'viral
replication, allowing potential accumulation of drug resistance mutations, or is replication
effectively abolished, requiring other explanations for viral breakthrough? Crucial to
understanding this issue is the development of methods for detecting low-level viral …
The development of highly active anti-retroviral therapy (HAART) has conferred great benefits to patients, but treatment failures are common. This leads to the question of what is going on with the virus during the period of successful control. Is there ongoing ‘covert’viral replication, allowing potential accumulation of drug resistance mutations, or is replication effectively abolished, requiring other explanations for viral breakthrough? Crucial to understanding this issue is the development of methods for detecting low-level viral replication during successful HAART. A recent study suggested that the abundance of 2-long terminal repeat (LTR) circles was a convenient marker [1]. This study suggested that 2-LTR circles, once formed in cells, were quite short-lived. Thus if 2-LTR circles could be detected in well suppressed patients, then they must indicate recent new infection resulting from ongoing replication. Unfortunately, more recent work, including a study by Brussel et al. in this issue of AIDS, indicate that this marker is in fact unreliable and should not be used in future studies. The data supporting the initial proposal and the subsequent reassessment are summarized below.
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