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1. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells

Author

Hiroshi Takata, Juyeon C. Kakazu, Julie L. Mitchell, Eugene Kroon, Donn J. Colby, Carlo Sacdalan, Hongjun Bai, Philip K. Ehrenberg, Aviva Geretz, Supranee Buranapraditkun, Suteeraporn Pinyakorn, Jintana Intasan, Somporn Tipsuk, Duanghathai Suttichom, Peeriya Prueksakaew, Thep Chalermchai, Nitiya Chomchey, Nittaya Phanuphak, Mark de Souza, Nelson L. Michael, Merlin L. Robb, Elias K. Haddad, Trevor A Crowell, Sandhya Vasan, Victor G. Valcour, Daniel C. Douek, Rasmi Thomas, Morgane Rolland, Nicolas Chomont, Jintanat Ananworanich, Lydie Trautmann, Nipat Teeratakulpisarn, Supanit Pattanachaiwit, Somchai Sriplienchan, Ponpen Tantivitayakul, Ratchapong Kanaprach, Kiat Ruxrungtham, Netsiri Dumrongpisutikul, Ponlapat Rojnuckarin, Suthat Chottanapund, Kultida Poltavee, Tassanee Luekasemsuk, Hathairat Savadsuk, Suwanna Puttamsawin, Khunthalee Benjapornpong, Nisakorn Ratnaratorn, Kamonkan Tangnaree, Chutharat Munkong, Rommanus Thaimanee, Patcharin Eamyoung, Sasiwimol Ubolyam, Sukalya Lerdlum, Sopark Manasnayakorn, Rugsun Rerknimitr, Sunee Sirivichayakul, Phandee Wattanaboonyongcharoen, Jessica Cowden, Alexandra Schuetz, Siriwat Akapirat, Nampueng Churikanont, Saowanit Getchalarat, Denise Hsu, Ellen Turk, Oratai Butterworth, Mark Milazzo, Leigh Anne Eller, Julie Ake, Serena Spudich, CAPT Lawrence Fox, Silvia Ratto-Kim, Victor DeGruttola, Yotin Chinvarun, Pasiri Sithinamsuwan, James Fletcher, and Bruce Shiramizu

Subjects
HIV, Antiretroviral therapy, CD8 T cells, Cell differentiation, TCF-1, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Harnessing CD8+ T cell responses is being explored to achieve HIV remission. Although HIV-specific CD8+ T cells become dysfunctional without treatment, antiretroviral therapy (ART) partially restores their function. However, the extent of this recovery under long-term ART is less understood. Methods: We analyzed the differentiation status and function of HIV-specific CD8+ T cells after long-term ART initiated in acute or chronic HIV infection ex vivo and upon in vitro recall. Findings: ART initiation in any stage of acute HIV infection promoted the persistence of long-lived HIV-specific CD8+ T cells with high expansion (P

Published
2022
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2. HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART

Author

Jintanat Ananworanich, Nicolas Chomont, Leigh Ann Eller, Eugene Kroon, Sodsai Tovanabutra, Meera Bose, Martin Nau, James L.K. Fletcher, Somporn Tipsuk, Claire Vandergeeten, Robert J. O'Connell, Suteeraporn Pinyakorn, Nelson Michael, Nittaya Phanuphak, and Merlin L. Robb

Subjects
Acute HIV infection, Art, HIV DNA, Reservoir, Persistence, Medicine, Medicine (General), R5-920
Abstract

HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM−) stage, that is ≤2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA.

Published
2016
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3. HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART

Author

Suteeraporn Pinyakorn, Merlin L. Robb, Jintanat Ananworanich, Eugene Kroon, Nicolas Chomont, James L. K. Fletcher, Nelson L. Michael, Claire Vandergeeten, Somporn Tipsuk, Sodsai Tovanabutra, Leigh Ann Eller, Meera Bose, Robert J. O'Connell, Martin E. Nau, and Nittaya Phanuphak

Subjects
0301 basic medicine, Adult, Male, Genotype, Anti-HIV Agents, Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, Biology, medicine.disease_cause, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, Persistence, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Proviruses, HIV DNA, Antiretroviral Therapy, Highly Active, medicine, Humans, 030212 general & internal medicine, Young adult, Reservoir, Acute HIV infection, lcsh:R5-920, lcsh:R, virus diseases, General Medicine, Viral Load, Virology, Antiretroviral therapy, Set point, 3. Good health, CD4 Lymphocyte Count, 030104 developmental biology, Immunology, DNA, Viral, HIV-1, Leukocytes, Mononuclear, RNA, Viral, Female, lcsh:Medicine (General), Viral load, Art, Research Paper
Abstract

HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM −) stage, that is ≤ 2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA., Highlights • The HIV DNA set-point is established early in acute HIV infection. • Over three years without antiretroviral therapy, persons with acute HIV infection have total HIV DNA in peripheral blood mononuclear cells that is 300-fold and integrated HIV DNA that is 100-fold higher than those on treatment. • Early antiretroviral therapy provides an opportunity to markedly reduce proviral HIV DNA burden, HIV is difficult to cure because it infects long-lived cells in the body, also called “reservoirs”. Having a small HIV reservoir size may benefit health. We show that HIV DNA in peripheral blood cells, a marker of the HIV reservoir size, establishes a set-point level during the first 6 weeks of infection and changes little over time without HIV medications. However, if HIV medications are started early, the reservoir size declines rapidly, and is 300-fold lower than that seen in untreated persons. Currently the most effective way to significantly lower the HIV reservoir size is with very early treatment.

Published
2016

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