Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus
Author:
Massanella Marta1, Puthanakit Thanyawee23, Leyre Louise1, Jupimai Thidarat2, Sawangsinth Panadda4, de Souza Mark4, Suntarattiwong Piyarat5, Kosalarksa Pope6, Borkird Thitiporn7, Kanjanavanit Suparat8, Chokephaibulkit Kulkanya9, Hansudewechakul Rawiwan10, Petdachai Witaya11, Mitchell Julie L121314, Robb Merlin L1213, Trautmann Lydie121314, Ananworanich Jintanat5121315, Chomont Nicolas1, Bunupuradah Torsak, Kerr Stephen, Ubolyam Sasiwimol, Mahanontharit Apicha, Laopraynak Naphassanant, Klaytong Preeyarach, Suwanlerk Tulathip, Pitimahajanaka Thita, Kasipong Naruporn, Noppakaorattanamanee Thornthan, Nanthapisal Kesdao, Iampornsin Thatri, Burichai Sasithorn, Jummanee Yupawadee, Soongpankeeree Sudarat, Intawan Monta, Theerawat Tuangthip, Moonwong Juthamanee, Srimuen Patchareeyawan, Saisaengjan Chutima, Prasitsuebsai Wasana, Jantarabenjakul Watsamon, Anugulruengkitt Suvaporn, Methanggool Umaporn, Sirikutt Pugpen, Leowsrisook Pimsiri, Na Nakorn Yosawadee, Sassungnune Naruemon, Wongmayurachat Kanokkarn, Kakkaew Chanasda, Rattanamanee Somjai, Yentang Manee, Panyim Patcha, Punyim Janyarak, Namwong Thida, Kamphaengkham Siripim, Chaisri Supanpilat, Khongponoi Areerat, Saksawad Ratchanee, Sukhaphan Usa, Laeyuheem Arena, Jourdain Gonzague, Ngo-Giang-Huong Nicole, Sirivichayakul Sunee, Maldarelli Frank, Palmer Sarah, Martin Michael, Lolekha Rangsima, Naiwatanakul Thananda, Faikratok Worawan, Baipluthong Benjamas, Teewunda Danai, Boonsuk Sarawut, Tonputsa Chaweewan, Tangpong Pariwat, Rojanawiwat Archawin, Thaisri Hansa, Puangtubtim Wiroi, Boonrossak Chaidan, Ongwandee Sumet, Chaifoo Walairat, Lertpiriyasuwat Cheewanan, Pawapootarnont Patcharaporn, Chucherd Jiraporn, Moonwong Juthamanee, Samleerat Tanawan, Chaiwut Suchada, Pinyakorn Suteeraporn, Butterworth Oratai, Ouellette Madelaine, Michael Nelson, Gramzinski Robert,
Affiliation:
1. Centre de Recherche du Centre hospitalier de l’Université de Montréal and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Canada 2. Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 3. HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 4. SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 5. Queen Sirikit National Institute of Child Health, Bangkok, Thailand 6. Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand 7. Hat Yai Hospital, Songkla, Thailand 8. Nakornping Hospital, Chiang Mai, Thailand 9. Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 10. Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand 11. Phrachomklao Hospital, Petchaburi, Thailand 12. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA 13. United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA 14. Vaccine and Gene Therapy Institute, Oregon Health and Science University, Hillsboro, Oregon, USA 15. Bill & Melinda Gates Medical Research Institute, Cambridge, Massachusetts, USA
Abstract
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.
Funder
Canadian Institutes of Health Research NIH
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
14 articles.
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