Multiple Variants Indicate Poor Clinical Outcomes for HIV-1 Infection

Researchers target new opportunities for preventive interventions.

Findings from a paper published in the journal Nature Medicine indicate that HIV-1 infection with multiple founder variants points to poorer clinical outcomes than infection with a single variant.

The study researched large sample sets from 2 important HIV vaccine efficacy trials in Thailand to evaluate whether genetic characteristics of the founder viral populations could influence markers of clinical outcomes. They specifically studied viral loads and CD4 T-cell counts against measures of HIV-1 diversity.

In both studies, it was observed that subjects who had multiple founder viruses had significantly higher mean viral loads.

“Our results bring into sharp focus how the earliest interactions between virus and host have a profound impact on the course of the entire disease,” said senior author Morgane Rolland, PhD, of the Military HIV Research Program (MHRP), Walter Reed Army Institute of Research.

The researchers tested the association between HIV-1 diversity and markers of disease progression by using 2 large data sets of viral sequences. The analysis included 63 patients infected with HIV-1 subtype B and 100 patients infected with CRF01_AE from the 2 Thailand studies, all of whom had viral load and CD4 T-cell measurements in the absence of antiretroviral therapy.

“When studying the host response early after infection, we are looking at 2 types of infection. An homogeneous viral population will evolve in a stepwise manner, whereas the presence of 2 or more viral variants can immediately foster complex viral evolutionary processes,” Dr. Rolland said.

The findings point out new opportunities for analyzing the effect of preventive interventions, including the development of new analysis methods that will take viral diversity measures into account.

“This study emphasizes the value of vaccine efficacy trials for gathering rich datasets—even if a trial fails to show efficacy, the data may be used to investigate important questions regarding HIV pathogenesis which informs next steps for HIV vaccine development,” said Col. Nelson Michael, MHRP Director.