Dr. Brahim Aissani, research assistant professor in the department of epidemiology at the University of Alabama at Birmingham, recently evaluated the impact of mitochondrial DNA (mtDNA) lineages (called mtDNA haplogroups) on virologic and immunological outcomes of HIV infection, using data from Highly Active Antiretroviral Therapy (HAART)-naive African American adolescent participants in the Reaching for Excellence in Adolescent Care and Health (REACH) study. Co-investigators are department colleagues Dr. Sadeep Shrestha, associate professor; Dr. Howard W. Wiener, statistician II; Dr. Craig M. Wilson, professor; and Dr. Richard A. Kaslow, professor emeritus; as well as Dr. Jianming Tang, professor in UAB’s division of infectious diseases.
[Photo: Dr. Brahim Aissani]
In the study, mtDNA haplogroups were determined by DNA sequencing and their predictive value on HIV outcomes were evaluated in statistical models adjusted for the effects of other factors known to influence HIV progression.
This research group reported that the mtDNA L2 lineage—a group composed of L2a, L2b, and L2e mtDNA haplogroups in the studied population— is associated with a steeper decline of CD4+ T cells (loss of 7-9 cells per month) during the clinical follow-up preceding HAART initiation. However, no strong association was observed between the tested mtDNA haplogroups and set-point viral load, an early marker of HIV disease progression. This finding concurs with the published data in the AIDS Clinical Trials Group study 384 implicating the L2 lineage with slower CD4+ T-cell recovery after antiretroviral therapy in African Americans.
The team concluded that, whereas the present data show that the L2 lineage is associated with unfavorable immunological outcomes of HIV infection, its phylogenetic divergence from J and U5a, two lineages associated with accelerated HIV progression in European Americans, raises the possibility that interactions between variants of mitochondrial and nuclear gene products drive HIV progression. Disentangling the effects of mitochondrial and nuclear gene variants on the outcomes of HIV infection is an important step toward a better understanding of HIV/AIDS pathogenesis and pharmacogenomics.
“Mitochondrial DNA Variation and Virologic and Immunological HIV Outcomes in African Americans” was published in June in the journal AIDS.