Research ArticleHIV

Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile

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Science Translational Medicine  27 Nov 2019:
Vol. 11, Issue 520, eaax7350
DOI: 10.1126/scitranslmed.aax7350

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Early to treat, early to thrive

Timing of antiretroviral therapy (ART) initiation for HIV can influence viral reservoir seeding and also the immune response, but this has not been well characterized in neonatal HIV infection. To discern how ART affects neonates, Garcia-Broncano et al. longitudinally studied infants from Botswana who were placed on ART hours or months after birth. They discovered that early initiation of therapy reduces seeding of the viral reservoir and also modulated NK cell and T cell responses to HIV. Their results show that immediate ART initiation, even earlier than the current guidelines of a few weeks, could provide real benefit to infants with HIV.


Neonatal HIV-1 infection is associated with rapidly progressive and frequently fatal immune deficiency if left untreated. Immediate institution of antiretroviral therapy (ART), ideally within hours after birth, may restrict irreversible damage to the developing neonatal immune system and possibly provide opportunities for facilitating drug-free viral control during subsequent treatment interruptions. However, the virological and immunological effects of ART initiation within hours after delivery have not been systematically investigated. We examined a unique cohort of neonates with HIV-1 infection from Botswana who started ART shortly after birth and were followed longitudinally for about 2 years in comparison to control infants started on treatment during the first year after birth. We demonstrate multiple clear benefits of rapid antiretroviral initiation, including an extremely small reservoir of intact proviral sequences, a reduction in abnormal T cell immune activation, a more polyfunctional HIV-1–specific T cell response, and an innate immune profile that displays distinct features of improved antiviral activity and is associated with intact proviral reservoir size. Together, these data offer rare insight into the evolutionary dynamics of viral reservoir establishment in neonates and provide strong empirical evidence supporting the immediate initiation of ART for neonates with HIV-1 infection.

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