Immune correlates of HIV-1 reservoir cell decline in early-treated infants

Ciputra Adijaya Hartana; Pilar Garcia-Broncano; Yelizaveta Rassadkina; Xiaodong Lian; Chenyang Jiang; Kevin B Einkauf; Kenneth Maswabi; Gbolahan Ajibola; Sikhulile Moyo; Terence Mohammed; Comfort Maphorisa; Joseph Makhema; Yuko Yuki; Maureen Martin; Kara Bennett; Patrick Jean-Philippe; Mathias Viard; Michael D Hughes; Kathleen M Powis; Mary Carrington; Shahin Lockman; Ce Gao; Xu G Yu; Daniel R Kuritzkes; Roger Shapiro; Mathias Lichterfeld

doi:10.1016/j.celrep.2022.111126

Immune correlates of HIV-1 reservoir cell decline in early-treated infants

Cell Rep. 2022 Jul 19;40(3):111126. doi: 10.1016/j.celrep.2022.111126.

Authors

Ciputra Adijaya Hartana¹, Pilar Garcia-Broncano¹, Yelizaveta Rassadkina², Xiaodong Lian¹, Chenyang Jiang¹, Kevin B Einkauf², Kenneth Maswabi³, Gbolahan Ajibola³, Sikhulile Moyo³, Terence Mohammed³, Comfort Maphorisa³, Joseph Makhema³, Yuko Yuki⁴, Maureen Martin⁴, Kara Bennett⁵, Patrick Jean-Philippe⁶, Mathias Viard⁴, Michael D Hughes⁷, Kathleen M Powis⁸, Mary Carrington⁹, Shahin Lockman¹⁰, Ce Gao², Xu G Yu¹¹, Daniel R Kuritzkes¹², Roger Shapiro¹³, Mathias Lichterfeld¹⁴

Affiliations

¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
³ Botswana - Harvard AIDS Institute Partnership, Gaborone, Botswana.
⁴ Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 20892, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁵ Bennett Statistical Consulting, Inc., Ballston Lake, NY 12019, USA.
⁶ Division of AIDS, NIAID, NIH, Rockville, MD 20852, USA.
⁷ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁸ Harvard Medical School, Boston, MA 02115, USA; Botswana - Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA.
⁹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 20892, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁰ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Botswana - Harvard AIDS Institute Partnership, Gaborone, Botswana.
¹¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
¹² Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
¹³ Harvard Medical School, Boston, MA 02115, USA; Botswana - Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹⁴ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: mlichterfeld@partners.org.

Abstract

Initiation of antiretroviral therapy (ART) in infected neonates within hours after birth limits viral reservoir seeding but does not prevent long-term HIV-1 persistence. Here, we report parallel assessments of HIV-1 reservoir cells and innate antiviral immune responses in a unique cohort of 37 infected neonates from Botswana who started ART extremely early, frequently within hours after birth. Decline of genome-intact HIV-1 proviruses occurs rapidly after initiation of ART and is associated with an increase in natural killer (NK) cell populations expressing the cytotoxicity marker CD57 and with a decrease in NK cell subsets expressing the inhibitory marker NKG2A. Immune perturbations in innate lymphoid cells, myeloid dendritic cells, and monocytes detected at birth normalize after rapid institution of antiretroviral therapy but do not notably influence HIV-1 reservoir cell dynamics. These results suggest that HIV-1 reservoir cell seeding and evolution in early-treated neonates is markedly influenced by antiviral NK cell immune responses.

Keywords: CP: Immunology; CP: Microbiology; HIV reservoir; NK cells; innate immune responses; intact HIV-1 proviruses; pediatric HIV-1 infection.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural

MeSH terms

Antiviral Agents / therapeutic use
CD4-Positive T-Lymphocytes
HIV Infections*
HIV Seropositivity*
HIV-1*
Humans
Immunity, Innate
Infant, Newborn
Killer Cells, Natural

Substances

Antiviral Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding