UKZN Researchers help solve Puzzle about the HIV/AIDS Epidemic

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Scientists at UKZN believe they may have solved a riddle that has baffled HIV and AIDS researchers for some time.

It involves one of the defining characteristics of the HIV and AIDS epidemic - the existence of multiple genetic strains known as subtypes or clades that are unevenly spread throughout the world.

Scientists have argued and puzzled over whether there are biological differences between subtypes that may explain their uneven distribution, and why some subtypes are spreading faster than others. 

There is now some clarity following UKZN studies.

In a recent public lecture, investigator at the KwaZulu-Natal Research for Tuberculosis and HIV and Victor Daitz Chair in HIV/TB Research, Professor Thumbi Ndung’u, presented a summary of a series of studies in which his team investigated biological differences between HIV-1 subtypes, focusing on the Gag and Nef genes that are important for HIV replication. 

Samples were collected from individuals infected with different subtypes that were not yet on antiretroviral therapy, and laboratory assays were performed to measure virus replication or known functions of the Gag or Nef proteins. 

The work focused on subtype B (common in Europe and North America) and subtypes A, C, D and intersubtype recombinants found in sub-Saharan Africa. 

They found that subtypes B, D and intersubtype recombinants were consistently able to replicate better or show better function when compared to subtypes A or C.  A fascinating finding from these studies was that subtype C, which is the predominant one in the global epidemic and in southern Africa, the region worst affect by the HIV and AIDS epidemic, always replicated poorer or performed the worst in the functional laboratory assays performed, whereas subtype B performed the best.  In a comparison of subtypes A and D from East Africa, subtype A was always poorer in assay performance than subtype D. 

The researchers concluded that there is a hierarchy of HIV subtype fitness with subtypes B, D and recombinants the most fit viruses whereas A and C are the least fit viruses. They say this is consistent with subtypes B and D being associated with faster disease progression whereas A and C are less pathogenic (or more attenuated) and may therefore be associated with slower disease progression. 

Interestingly, Ndung’u proposed that decreased pathogenicity may be advantageous for the epidemic spread of subtypes A and C since individuals infected with these viruses may live longer and transmit more.  He also proposed that there may be other viral factors that enhance the transmission efficiency of subtypes A and C that will require further investigation.

Ndung’u credited a number of researchers in his laboratory who contributed to this ground-breaking work, including Dr Jaclyn Mann, Dr Denis Chopera and Ms Marion Kiguoya. 

The work was a collaborative effort between South African, Canadian, Kenyan and Ugandan researchers. The work helps to explain how HIV affects the rate of disease progression in individuals and how in general epidemics spread and change over time.

Ndung’u holds the South African Research Chair in Systems Biology of HIV/AIDS and is an International Early Career Scientist of the Howard Hughes Medical Institute.  His laboratory works on anti-HIV and TB immune mechanisms and vaccine development strategies and he has a special interest in capacity development for biomedical research in Africa.

Nombuso Dlamini