Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease
Abstract Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict re...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54116-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849221090057912320 |
|---|---|
| author | Alton Barbehenn Lei Shi Junzhe Shao Rebecca Hoh Heather M. Hartig Vivian Pae Sannidhi Sarvadhavabhatla Sophia Donaire Caroline Sheikhzadeh Jeffrey Milush Gregory M. Laird Mignot Mathias Kristen Ritter Michael J. Peluso Jeffrey Martin Frederick Hecht Christopher Pilcher Stephanie E. Cohen Susan Buchbinder Diane Havlir Monica Gandhi Timothy J. Henrich Hiroyu Hatano Jingshen Wang Steven G. Deeks Sulggi A. Lee |
| author_facet | Alton Barbehenn Lei Shi Junzhe Shao Rebecca Hoh Heather M. Hartig Vivian Pae Sannidhi Sarvadhavabhatla Sophia Donaire Caroline Sheikhzadeh Jeffrey Milush Gregory M. Laird Mignot Mathias Kristen Ritter Michael J. Peluso Jeffrey Martin Frederick Hecht Christopher Pilcher Stephanie E. Cohen Susan Buchbinder Diane Havlir Monica Gandhi Timothy J. Henrich Hiroyu Hatano Jingshen Wang Steven G. Deeks Sulggi A. Lee |
| author_sort | Alton Barbehenn |
| collection | DOAJ |
| description | Abstract Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time. |
| format | Article |
| id | doaj-art-8b1fa10376d24d1298f9484c4aafb4a0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8b1fa10376d24d1298f9484c4aafb4a02024-11-24T12:33:45ZengNature PortfolioNature Communications2041-17232024-11-0115111210.1038/s41467-024-54116-1Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV diseaseAlton Barbehenn0Lei Shi1Junzhe Shao2Rebecca Hoh3Heather M. Hartig4Vivian Pae5Sannidhi Sarvadhavabhatla6Sophia Donaire7Caroline Sheikhzadeh8Jeffrey Milush9Gregory M. Laird10Mignot Mathias11Kristen Ritter12Michael J. Peluso13Jeffrey Martin14Frederick Hecht15Christopher Pilcher16Stephanie E. Cohen17Susan Buchbinder18Diane Havlir19Monica Gandhi20Timothy J. Henrich21Hiroyu Hatano22Jingshen Wang23Steven G. Deeks24Sulggi A. Lee25Department of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Biostatistics, University of California BerkeleyDepartment of Biostatistics, University of California BerkeleyDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of Experimental Medicine, University of California San FranciscoAccelevirDiagnosticsAccelevirDiagnosticsAccelevirDiagnosticsDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Biostatistics & Epidemiology, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoSan Francisco Department of Public HealthDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of Experimental Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Biostatistics, University of California BerkeleyDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoDepartment of Medicine, Division of HIV, Infectious Diseases & Global Medicine, University of California San FranciscoAbstract Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.https://doi.org/10.1038/s41467-024-54116-1 |
| spellingShingle | Alton Barbehenn Lei Shi Junzhe Shao Rebecca Hoh Heather M. Hartig Vivian Pae Sannidhi Sarvadhavabhatla Sophia Donaire Caroline Sheikhzadeh Jeffrey Milush Gregory M. Laird Mignot Mathias Kristen Ritter Michael J. Peluso Jeffrey Martin Frederick Hecht Christopher Pilcher Stephanie E. Cohen Susan Buchbinder Diane Havlir Monica Gandhi Timothy J. Henrich Hiroyu Hatano Jingshen Wang Steven G. Deeks Sulggi A. Lee Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease Nature Communications |
| title | Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease |
| title_full | Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease |
| title_fullStr | Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease |
| title_full_unstemmed | Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease |
| title_short | Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease |
| title_sort | rapid biphasic decay of intact and defective hiv dna reservoir during acute treated hiv disease |
| url | https://doi.org/10.1038/s41467-024-54116-1 |
| work_keys_str_mv | AT altonbarbehenn rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT leishi rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT junzheshao rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT rebeccahoh rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT heathermhartig rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT vivianpae rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT sannidhisarvadhavabhatla rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT sophiadonaire rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT carolinesheikhzadeh rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT jeffreymilush rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT gregorymlaird rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT mignotmathias rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT kristenritter rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT michaeljpeluso rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT jeffreymartin rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT frederickhecht rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT christopherpilcher rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT stephanieecohen rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT susanbuchbinder rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT dianehavlir rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT monicagandhi rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT timothyjhenrich rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT hiroyuhatano rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT jingshenwang rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT stevengdeeks rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease AT sulggialee rapidbiphasicdecayofintactanddefectivehivdnareservoirduringacutetreatedhivdisease |