Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART
Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C....
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-12-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.152526 |
| _version_ | 1811334816972406784 |
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| author | Veronica Obregon-Perko Katherine M. Bricker Gloria Mensah Ferzan Uddin Laura Rotolo Daryll Vanover Yesha Desai Philip J. Santangelo Sherrie Jean Jennifer S. Wood Fawn C. Connor-Stroud Stephanie Ehnert Stella J. Berendam Shan Liang Thomas H. Vanderford Katharine J. Bar George M. Shaw Guido Silvestri Amit Kumar Genevieve G. Fouda Sallie R. Permar Ann Chahroudi |
| author_facet | Veronica Obregon-Perko Katherine M. Bricker Gloria Mensah Ferzan Uddin Laura Rotolo Daryll Vanover Yesha Desai Philip J. Santangelo Sherrie Jean Jennifer S. Wood Fawn C. Connor-Stroud Stephanie Ehnert Stella J. Berendam Shan Liang Thomas H. Vanderford Katharine J. Bar George M. Shaw Guido Silvestri Amit Kumar Genevieve G. Fouda Sallie R. Permar Ann Chahroudi |
| author_sort | Veronica Obregon-Perko |
| collection | DOAJ |
| description | Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C.CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children. |
| first_indexed | 2024-04-13T17:14:48Z |
| format | Article |
| id | doaj.art-983674d7bb4541aa9e530e783bfd9106 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T17:14:48Z |
| publishDate | 2021-12-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-983674d7bb4541aa9e530e783bfd91062022-12-22T02:38:10ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-12-01623Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ARTVeronica Obregon-PerkoKatherine M. BrickerGloria MensahFerzan UddinLaura RotoloDaryll VanoverYesha DesaiPhilip J. SantangeloSherrie JeanJennifer S. WoodFawn C. Connor-StroudStephanie EhnertStella J. BerendamShan LiangThomas H. VanderfordKatharine J. BarGeorge M. ShawGuido SilvestriAmit KumarGenevieve G. FoudaSallie R. PermarAnn ChahroudiUnderstanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C.CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children.https://doi.org/10.1172/jci.insight.152526AIDS/HIVVirology |
| spellingShingle | Veronica Obregon-Perko Katherine M. Bricker Gloria Mensah Ferzan Uddin Laura Rotolo Daryll Vanover Yesha Desai Philip J. Santangelo Sherrie Jean Jennifer S. Wood Fawn C. Connor-Stroud Stephanie Ehnert Stella J. Berendam Shan Liang Thomas H. Vanderford Katharine J. Bar George M. Shaw Guido Silvestri Amit Kumar Genevieve G. Fouda Sallie R. Permar Ann Chahroudi Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART JCI Insight AIDS/HIV Virology |
| title | Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART |
| title_full | Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART |
| title_fullStr | Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART |
| title_full_unstemmed | Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART |
| title_short | Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART |
| title_sort | dynamics and origin of rebound viremia in shiv infected infant macaques following interruption of long term art |
| topic | AIDS/HIV Virology |
| url | https://doi.org/10.1172/jci.insight.152526 |
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