Publication: Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected with Human Immunodeficiency Virus
Issued Date
2021-08-01
Resource Type
ISSN
15376591
10584838
10584838
Other identifier(s)
2-s2.0-85109387587
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical Infectious Diseases. Vol.73, No.3 (2021), 427-438
Suggested Citation
Marta Massanella, Thanyawee Puthanakit, Louise Leyre, Thidarat Jupimai, Panadda Sawangsinth, Mark De Souza, Piyarat Suntarattiwong, Pope Kosalarksa, Thitiporn Borkird, Suparat Kanjanavanit, Kulkanya Chokephaibulkit, Rawiwan Hansudewechakul, Witaya Petdachai, Julie L. Mitchell, Merlin L. Robb, Lydie Trautmann, Jintanat Ananworanich, Nicolas Chomont Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected with Human Immunodeficiency Virus. Clinical Infectious Diseases. Vol.73, No.3 (2021), 427-438. doi:10.1093/cid/ciaa718 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78004
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Title
Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected with Human Immunodeficiency Virus
Author(s)
Marta Massanella
Thanyawee Puthanakit
Louise Leyre
Thidarat Jupimai
Panadda Sawangsinth
Mark De Souza
Piyarat Suntarattiwong
Pope Kosalarksa
Thitiporn Borkird
Suparat Kanjanavanit
Kulkanya Chokephaibulkit
Rawiwan Hansudewechakul
Witaya Petdachai
Julie L. Mitchell
Merlin L. Robb
Lydie Trautmann
Jintanat Ananworanich
Nicolas Chomont
Thanyawee Puthanakit
Louise Leyre
Thidarat Jupimai
Panadda Sawangsinth
Mark De Souza
Piyarat Suntarattiwong
Pope Kosalarksa
Thitiporn Borkird
Suparat Kanjanavanit
Kulkanya Chokephaibulkit
Rawiwan Hansudewechakul
Witaya Petdachai
Julie L. Mitchell
Merlin L. Robb
Lydie Trautmann
Jintanat Ananworanich
Nicolas Chomont
Other Contributor(s)
Siriraj Hospital
Thai Red Cross Agency
Nakornping Hospital
Faculty of Medicine, Khon Kaen University
Oregon Health & Science University
HJF
Walter Reed Army Institute of Research
Queen Sirikit National Institute of Child Health
Centre Hospitalier de L'Universite de Montreal
Faculty of Medicine, Chulalongkorn University
Bill and Melinda Gates Medical Research Institute
Hat Yai Hospital
Chiangrai Prachanukroh Hospital
Phrachomklao Hospital
Thai Red Cross Agency
Nakornping Hospital
Faculty of Medicine, Khon Kaen University
Oregon Health & Science University
HJF
Walter Reed Army Institute of Research
Queen Sirikit National Institute of Child Health
Centre Hospitalier de L'Universite de Montreal
Faculty of Medicine, Chulalongkorn University
Bill and Melinda Gates Medical Research Institute
Hat Yai Hospital
Chiangrai Prachanukroh Hospital
Phrachomklao Hospital
Abstract
Background: Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown. Methods: We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings. Results: Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P <. 020 and P <. 001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P <. 01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis. Conclusions: Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.