Continuous Prophylactic Antiretrovirals/Antiretroviral Therapy Since Birth Reduces Seeding and Persistence of the Viral Reservoir in Children Vertically Infected With Human Immunodeficiency Virus
Authors: Massanella Marta , Puthanakit Thanyawee , Leyre Louise , Jupimai Thidarat , Sawangsinth Panadda , de Souza Mark , Suntarattiwong Piyarat , Kosalarksa Pope , Borkird Thitiporn , Kanjanavanit Suparat , Chokephaibulkit Kulkanya , Hansudewechakul Rawiwan , Petdachai Witaya , Mitchell Julie L , Robb Merlin L , Trautmann Lydie , Ananworanich Jintanat , Chomont Nicolas ,   RV474/HIVNAT194 and RV475/HIVNAT 209 Study Groups, 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 
Published: June 2020

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 &lt; .020 and P &lt; .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P &lt; .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.