A multinational research team has developed a test to measure the persistence of HIV in people who have been infected by strains of the virus found predominantly in Africa, providing a necessary tool in the search for a cure for HIV in a region with a very high burden of the disease.
The persistence of HIV in the body, in which HIV establishes latent viral reservoirs (LVRs) in the body, has presented one of the greatest challenges to developing a cure for HIV. LVRs are primarily made up of resting CD4+ T cells containing stably integrated HIV-1 proviruses, the majority of which are defective. However, a small number of genome-intact proviruses are present and may produce active viruses if antiretroviral treatment is interrupted.
"We are looking for a needle in a haystack: to achieve an HIV cure, we need to first find out whether any genome-intact proviruses remain in the body during antiretroviral treatment. Our new assay allows us to do this. Then we need to target and eliminate the intact DNA capable of producing new viruses," said the paper's lead author Dr. Guinevere Lee, assistant professor of virology in medicine in the division of infectious diseases and assistant professor of microbiology and immunology at Weill Cornell Medicine, in a statement.
The majority of research thus far on genome-intact proviruses and persistence has been done using samples from men infected with HIV-1 strain B, which is the most common subtype in North America and the European Union. However, the B strain is not the most common subtype globally; furthermore, the majority of people living with HIV in Africa are women. The A1 and D subtypes predominate in Africa. The D subtype is associated with faster disease progression, lower CD4+ T-cell count, and a faster rate of CD4+ T-cell decline, as well as higher mortality, making it a particularly aggressive strain.
In the journal Nature Communications, the research team discussed developing the assay by analyzing DNA from the CD4+ T cells of 16 women and seven men in Uganda, all of whom were receiving antiretroviral HIV treatment. Sequencing showed two predominant HIV-1 subtypes: A1 and D (a notoriously aggressive strain). The study also identified viral hybrids of A1 and D.
The team then modified the existing intact proviral DNA assay (IPDA) test designed to identify HIV subtype B proviruses (IPDA-B) to detect and capture the genetic diversity of subtypes A1 and D proviruses, referring to the modified assay as IPDA-A1D.
While the team's findings show that the composition of the proviral genetic landscape is broadly similar between subtypes A1, D, and B, suggesting that research targeting the LVRs will face the same challenges in Africa as in North America and Europe, the researchers emphasize that future studies are needed to determine if differences in the subtypes have effects on HIV-1 persistence, clearance, and reactivation. Moreover, they write, that their work "will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest."
