Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs
- Ghent University, Belgium
- Royal Free London NHS Foundation Trust, United Kingdom
Abstract
Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using PCR-based techniques in blood and tissue of early treated seroconverters, late treated patients, ART-naïve seroconverters and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced total and integrated HIV-1 DNA levels compared to later treatment initiation, but not reaching the low levels of LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (unspliced RNA) and enhanced immune preservation (CD4/CD8) reminiscent of LTNPs were found in early compared to late treated patients. This suggests that early treatment is associated with some immuno-virological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure.
Article and author information
Author details
Ethics
Human subjects: Patient written informed consent was obtained from all the study participants.The study was approved by the Ethical Committee of Ghent University Hospital (Reference number: B670201317826) and Royal Free Hospital (Reference number: 13/LO/0729).
Copyright
© 2015, Malatinkova et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,261
- views
-
- 427
- downloads
-
- 32
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs
eLife 4:e09115.
https://doi.org/10.7554/eLife.09115
Further reading
-
- Microbiology and Infectious Disease
A combination of imaging techniques reveals how herpes simplex virus type 1 assembles within infected cells, highlighting the roles of essential viral proteins in viral assembly and exit.
-
- Microbiology and Infectious Disease
Mycobacterium tuberculosis (Mtb) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular Mtb utilize host-derived lipids to maintain infection, the role of macrophage lipid processing on the bacteria’s ability to access the intracellular lipid pool remains undefined. We utilized a CRISPR-Cas9 genetic approach to assess the impact of sequential steps in fatty acid metabolism on the growth of intracellular Mtb. Our analyses demonstrate that macrophages that cannot either import, store, or catabolize fatty acids restrict Mtb growth by both common and divergent antimicrobial mechanisms, including increased glycolysis, increased oxidative stress, production of pro-inflammatory cytokines, enhanced autophagy, and nutrient limitation. We also show that impaired macrophage lipid droplet biogenesis is restrictive to Mtb replication, but increased induction of the same fails to rescue Mtb growth. Our work expands our understanding of how host fatty acid homeostasis impacts Mtb growth in the macrophage.
