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Immune correlates of HIV-1 reservoir cell decline in early-treated infants
Ciputra Adijaya Hartana1, Pilar Garcia-Broncano1, Yelizaveta Rassadkina2
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
Insights
Early antiretroviral therapy (ART) in neonates limits HIV-1 seeding but doesn't prevent persistence. Antiviral natural killer (NK) cell responses correlate with HIV-1 reservoir decline in infants receiving rapid ART.
Area of Science:
- Immunology
- Virology
- Neonatal care
Background:
- Initiating antiretroviral therapy (ART) shortly after birth is crucial for managing vertical HIV-1 transmission.
- Despite early ART, long-term HIV-1 persistence remains a challenge, necessitating a deeper understanding of early viral dynamics and immune responses.
Purpose of the Study:
- To investigate the impact of extremely early ART on HIV-1 reservoir cells and innate immune responses in neonates.
- To explore the relationship between NK cell populations and HIV-1 reservoir dynamics in infants receiving ART within hours of birth.
Main Methods:
- Parallel assessment of HIV-1 reservoir cells and innate immune responses in 37 infected neonates from Botswana.
- Analysis of NK cell subsets (CD57+, NKG2A-) and other innate immune cells (ILCs, MoDCs, monocytes).
- Correlation of viral dynamics with immune cell profiles post-ART initiation.
Main Results:
- Rapid decline of genome-intact HIV-1 proviruses observed after ART initiation.
- ART initiation was associated with increased CD57+ NK cells and decreased NKG2A- NK cells.
- Immune perturbations in ILCs, MoDCs, and monocytes normalized with rapid ART, but did not significantly impact HIV-1 reservoir dynamics.
Conclusions:
- Extremely early ART in neonates leads to a rapid decrease in HIV-1 proviruses.
- Antiviral NK cell responses, specifically changes in CD57 and NKG2A expression, are strongly associated with HIV-1 reservoir evolution in early-treated infants.
- NK cell-mediated immunity plays a significant role in controlling HIV-1 reservoir seeding and dynamics in neonates initiated on ART within hours of birth.
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.
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