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Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection.


ABSTRACT:

Background

Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks.

Methods

Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment.

Results

At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point.

Conclusion

These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.

SUBMITTER: de Bree GJ 

PROVIDER: S-EPMC5351995 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection.

de Bree Godelieve J GJ   Wheatley Adam K AK   Lynch Rebecca M RM   Prabhakaran Madhu M   Grijsen Marlous L ML   Prins Jan M JM   Schmidt Stephen D SD   Koup Richard A RA   Mascola John R JR   McDermott Adrian B AB  

PloS one 20170315 3


<h4>Background</h4>Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the me  ...[more]

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