Immunity to HIV in Early Life

Abstract

The developing immune system is adapted to the exposure to a plethora of pathogenic and non-pathogenic antigens encountered in utero and after birth, requiring a fine balance between protective immunity and immune tolerance. In early stages of life, this tolerogenic state of the innate and adaptive immune system and the lack of immunological memory render the host more susceptible to infectious pathogens like HIV. HIV pathogenesis is different in children, compared to adults, with more rapid disease progression and a substantial lack of control of viremia compared to adults. Plasma viral load remains high during infancy and only declines gradually over several years in line with immune maturation, even in rare cases where children maintain normal CD4 T-lymphocyte counts for several years without antiretroviral therapy (ART). These pediatric slow progressors also typically show low levels of immune activation despite persistently high viremia, resembling the phenotype of natural hosts of SIV infection. The lack of immunological memory places the fetus and the newborn at higher risk of infections; however, it may also provide an opportunity for unique interventions. Frequencies of central memory CD4+ T-lymphocytes, one of the main cellular reservoirs of HIV, are very low in the newborn child, so immediate ART could prevent the establishment of persistent viral reservoirs and result in “functional cure.” However, as recently demonstrated in the case report of the “Mississippi child” who experienced viral rebound after more than 2 years off ART, additional immunomodulatory strategies might be required for sustained viral suppression after ART cessation. In this review, we discuss the interactions between HIV and the developing immune system in children and the potential implications for therapeutic and prophylactic interventions.

International AIDS Society global scientific strategy: towards an HIV cure 2016

“…The dynamics of HIV persistence in children are probably different than those in adults, owing to a number of factors such as the types and numbers of target cells, efficiency in clearing HIV-infected cells, and pharmacokinetics of ART in blood and tissues. Little is known about the development of the newborn and infant innate and adaptive immune system, and about the role of immune activation, homeostasis, inflammation, and viral and host factors in the establishment and maintenance of HIV latency 70 . Early ART can preserve normal development of B and T cells, as demonstrated by the ability to mount immune responses against childhood vaccines.…”

Immune activation and paediatric HIV-1 disease outcome

“…This Th2-directed bias in early life is likely to be an adaptation that has evolved to prevent harmful pro-inflammatory Th1 responses against maternal allo-antigens while in-utero (8) and the plethora of newly encountered environmental antigens after birth (3). However, this ‘approach’ compromises immunity to intracellular pathogens such as HIV (9). …”

Analytical treatment interruption after short-term anti-retroviral therapy in a postnatally SHIV infected infant rhesus macaque model

“…Previous studies have claimed that infants may have impaired immune responses to HIV infection compared to adults (40). However, we previously demonstrated that vaccination of infants can induce robust HIV Env-specific IgG responses (41).…”