Bisher AKIL, MD

Virus load is undetectable, but active virus still?

In HIV, Immune System on August 23, 2016 at 4:16 pm

HIV-infected patients taking antiretroviral medications with undetectable viral loads continue to have detectable HIV DNA in CD 4+ cells despite many years of therapy. Previous studies have found that most of that HIV DNA is defective and unable to replicate, a veritable “defective” of proviruses (the genetic material of a virus as incorporated into, and able to replicate with, the genome of a host cell). The current consensus view of the “defective” proviruses is that these are dead-end products that do not give rise to progeny (offspring) virus and thus collectively represent a “graveyard” of viruses.Now, a careful analysis reveals that these defective proviruses may not quite be as “dead” as we thought.

Investigators have now studied HIV DNA proviruses from four patients with undetectable plasma viral loads. As expected, the patients had defective proviruses with deletions or lethal mutations. Surprisingly, when cytoplasmic RNA from these patients was sequenced, the investigators found novel RNA transcripts matching the defective proviruses. These transcripts appeared to be capable of producing viral proteins. Investigators  propose that the proviruses persistently present in combination antiretroviral therapy-treated patients are not defective in a conventional sense, but rather represent incomplete forms of proviruses encoding translationally competent HIV-RNA transcripts. Strategies directed toward curing HIV-1 infection and eliminating the state of persistent immune activation need to include approaches designed to eliminate cells harboring such proviruses.

 

Appeared in JWatch August 5, 2016

Citation(s):Imamichi H et al. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc Natl Acad Sci U S A 2016 Aug 2; 113:8783. (http://dx.doi.org/10.1073/pnas.1609057113)

 

Comments: this could explain the presence of viral activation ( seen by careful analysis of T-cell panel, mediators, ..etc) in those with undetectable plasma virus load. The question remains, should this be controlled, can it lead to an increase in CD4+ counts in those with undetectable virus load? This is probably one of the biggest clinical hurdles left_BA

 

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