Children with Nonprogressing HIV Could Shed Light on New Treatment Strategies

A cohort of HIV-positive children in southern Africa, despite having never been treated for HIV, retain near-normal immune systems and lack any signs of disease progression to AIDS, according to researchers.

Similar circumstances have been observed in sooty mangabey and African green monkeys infected with the simian immunodeficiency virus (SIV), which also maintain high viral loads without disease progression.  
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“Although most people that get infected with HIV develop AIDS, rare individuals maintain immune function in the presence of virus, a phenomenon also seen in natural hosts of the closely related SIV,” the researchers explained.

In order to better understand the mechanisms behind this lack of disease progression, researchers examined data from 170 nonprogressing antiretroviral therapy-naïve children aged 5 years and older who maintained normal-for-age CD4 T cell counts and low immune activation levels despite high viral load.

While broadly neutralizing antibody responses and strong virus-specific T cell activity were present in most participants, this, the researchers noted, did not drive nonprogression.

Reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were also observed in the nonprogressors.

“These children therefore express 2 cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys—low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells—suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults,” the researchers concluded.

“The immune mechanisms described in these patients shed light on HIV pathogenesis, which may help develop future treatments.”

—Michael Potts

Reference:
Muenchhoff M, Adland E, Karimanzira O, et al. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection [published online September 28, 2016]. doi:10.1126/scitranslmed.aag1048