Why Some HIV-Positive Children Never Progress to AIDS

Between 5% and 10% of prenatally infected HIV-positive children do not end up developing AIDS.

In a new study published in Science Translational Medicine, researchers categorized the immunological responses of a cohort containing ‘non-progressor’ children in South Africa with an average age of just under 8 1/2 —years-old.

The results of the study showed that these children have high concentrations of circulating HIV particles, however, their immune systems remained fully functional.

“Interestingly however, these infected but healthy children exhibit low levels of immune activation,” said researcher Maximilian Muenchhoff. “In addition, while the spectrum of cell types that contain the virus — the so called viral reservoir – is very complex it is predominantly restricted to short-lived CD4+ T cells in these young non-progressors.”

Researchers also found that a majority of these children had high levels of potent and broadly neutralizing antibodies directed against HIV. This immune response in healthy HIV-infected children resembled the response seen in more than 40 species of African monkeys, which are the natural hosts of simian immunodeficiency virus (SIV) that HIV is derived from.

In these primates, the virus is able to replicate efficiently and, like in the non-progressor children, the infected animals show no signs of immune dysfunction. Furthermore, short-lived CD4+ T cells serve as the primary viral reservoir, and levels of immune activation are low.

In contrast, the vast majority of both adults and children with HIV-infected AIDS show signs of chronic activation of the immune system. Additionally, this disease has been associated with long-term complications, such as an increased risk of cardiovascular disease, and will continue to persist, even under antiretroviral therapy.

In the new study, 170 participants in the cohort were infected with HIV by mother-to-child transmission. However, since the children were asymptomatic, in most cases they did not know they were infected until several years later when their mothers developed AIDS and sought medical attention.

The authors noted that the findings are of particular interest for the development of HIV vaccines, and may provide suggestions towards potential interventions for patients with chronic HIV.

“This is a remarkable clinical study from the epicenter of the HIV pandemic,” said researcher Oliver T. Keppler. “The ability of these children to maintain an intact immune system in the face of ongoing viral replication and in the absence of antiretroviral therapy can provide us with new insights into hitherto unknown defense mechanisms, which could eventually benefit other HIV patients.”