Approximately 2.1 million children younger than age 15 years were living with human immunodeficiency virus type 1 (HIV-1) infection in 2016, including 160,000 newly infected children. In the same year, nearly 120,000 children died from acquired immunodeficiency syndrome (AIDS)-related illnesses, and hundreds of thousands more children lost one or both parents to HIV. HIV clearly continues to exert a devastating effect on global child health. Nevertheless, expanded access to antiretroviral therapy (ART) is turning the tide of this epidemic. The numbers of children newly infected with HIV-1 and children dying of AIDS-related illness in 2016 were approximately half what they were in 2010. For many children with access to ART, HIV-1 has become a manageable, chronic disease rather a certain cause of early death.
PATHOGENESIS AND EPIDEMIOLOGY
HIV-1 is a retrovirus that preferentially infects activated CD4+ T lymphocytes expressing the cytokine receptors CCR5 or CXCR4, which act as viral co-receptors. Acute HIV infection is marked by high-level viral replication and cytolytic destruction of CD4+ T lymphocytes, particularly the abundant gut-associated CD4+CCR5+ T lymphocytes. This is followed by gradual attrition of circulating CD4+ T-lymphocyte populations as disease progresses. The mechanisms by which HIV-1 infection causes this CD4+ cell decline is not completely established, although possibilities include ongoing lytic infection, destruction of infected cells by host antiviral immune mechanisms, and death or dysfunction of lymphocyte precursors or accessory cells in the thymus and lymph nodes.
Once established, HIV-1 infection invariably persists. In the absence of ART, HIV continuously replicates and infects newly activated CD4+ T lymphocytes. Ongoing generation of viral variants bearing escape mutations in immune epitopes contributes to evasion of host-neutralizing antibodies and cytotoxic T cells. Additionally, HIV-1 genomes integrate into the host chromosomal DNA to establish latent infection. Resting memory CD4+ T lymphocytes appear to be the most important reservoir of latent HIV-1 infection. These cells stably harbor HIV-1 genomes even after years of viral suppression with ART, allowing viral rebound when ART is stopped. Early initiation of combination antiretroviral therapy (cART) may limit the extent of the latent viral reservoir. In addition to CD4+ T lymphocytes, other cells types such as tissue-resident macrophages can also be infected by HIV-1. These cells may also function as long-term viral reservoirs and contribute to organ-specific pathology, although some controversy remains. Even in individuals well controlled on cART, HIV-1 DNA may be recovered from brain, lung, liver, kidney, testes, and other tissues. HIV-1 -related pathology involves many organs, although it is often difficult to know whether injury is primarily a consequence of local virus infection, immune-mediated cytotoxic effects, or associated infectious complications.
The primary modes of HIV-1 transmission include sexual contact, percutaneous exposure, and mother-to-child transmission. The vast majority of pediatric infections have been acquired by mother-to-child transmission, which can occur in utero, at the time of delivery, or postnatally via breast milk. In the absence of ART and other protective measures, ...