Predictors of SIV recrudescence following antiretroviral treatment interruption
There is currently a need for proxy measures of the HIV rebound competent reservoir (RCR) that can predict viral rebound after combined antiretroviral treatment (cART) interruption. In this study, macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27 days post-i...
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doaj-2c232d9c0c7d480abdd0f0ab8a6a7a662021-05-05T18:02:22ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.49022Predictors of SIV recrudescence following antiretroviral treatment interruptionMykola Pinkevych0Christine M Fennessey1Deborah Cromer2Carolyn Reid3Charles M Trubey4Jeffrey D Lifson5Brandon F Keele6Miles P Davenport7https://orcid.org/0000-0002-4751-1831Infection Analytics Program, Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, AustraliaAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United StatesInfection Analytics Program, Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, AustraliaAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United StatesAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United StatesAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United StatesAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United StatesInfection Analytics Program, Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, AustraliaThere is currently a need for proxy measures of the HIV rebound competent reservoir (RCR) that can predict viral rebound after combined antiretroviral treatment (cART) interruption. In this study, macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27 days post-infection, leading to the establishment of different levels of viral dissemination and persistence. Later treatment initiation led to higher SIV DNA levels maintained during treatment, which was significantly associated with an increased frequency of SIV reactivation and production of progeny capable of causing rebound viremia following treatment interruption. However, a 100-fold increase in SIV DNA in PBMCs was associated with only a 2-fold increase in the frequency of reactivation. These data suggest that the RCR can be established soon after infection, and that a large fraction of persistent viral DNA that accumulates after this time makes relatively little contribution to viral rebound.https://elifesciences.org/articles/49022HIVlatencyimmunity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mykola Pinkevych Christine M Fennessey Deborah Cromer Carolyn Reid Charles M Trubey Jeffrey D Lifson Brandon F Keele Miles P Davenport |
spellingShingle |
Mykola Pinkevych Christine M Fennessey Deborah Cromer Carolyn Reid Charles M Trubey Jeffrey D Lifson Brandon F Keele Miles P Davenport Predictors of SIV recrudescence following antiretroviral treatment interruption eLife HIV latency immunity |
author_facet |
Mykola Pinkevych Christine M Fennessey Deborah Cromer Carolyn Reid Charles M Trubey Jeffrey D Lifson Brandon F Keele Miles P Davenport |
author_sort |
Mykola Pinkevych |
title |
Predictors of SIV recrudescence following antiretroviral treatment interruption |
title_short |
Predictors of SIV recrudescence following antiretroviral treatment interruption |
title_full |
Predictors of SIV recrudescence following antiretroviral treatment interruption |
title_fullStr |
Predictors of SIV recrudescence following antiretroviral treatment interruption |
title_full_unstemmed |
Predictors of SIV recrudescence following antiretroviral treatment interruption |
title_sort |
predictors of siv recrudescence following antiretroviral treatment interruption |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-10-01 |
description |
There is currently a need for proxy measures of the HIV rebound competent reservoir (RCR) that can predict viral rebound after combined antiretroviral treatment (cART) interruption. In this study, macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27 days post-infection, leading to the establishment of different levels of viral dissemination and persistence. Later treatment initiation led to higher SIV DNA levels maintained during treatment, which was significantly associated with an increased frequency of SIV reactivation and production of progeny capable of causing rebound viremia following treatment interruption. However, a 100-fold increase in SIV DNA in PBMCs was associated with only a 2-fold increase in the frequency of reactivation. These data suggest that the RCR can be established soon after infection, and that a large fraction of persistent viral DNA that accumulates after this time makes relatively little contribution to viral rebound. |
topic |
HIV latency immunity |
url |
https://elifesciences.org/articles/49022 |
work_keys_str_mv |
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