Medical Academic: African human genome sequences represent the lowest number of all the human genomes that have been sequenced worldwide. How does this impact the care available for African HIV patients?

Prof Veron Ramsuran: So African human genomes represent only less than two percent of all human genomes that have been sequenced thus far, but we know very little about African genomes. To treat individuals from African descent we need to know more about their genetic structure so that we can determine which drugs can be given to those individuals as well as whether vaccines can be effective amongst various diseases that they are designed for.

Now, not knowing the genetic structure of these individuals doesn't allow us to give better treatment to those individuals. Also, it makes it very difficult to design new drugs in the future against individuals or diseases that are found in individuals of African descent. So more knowledge is required for the genetics of individuals of African descent.

Now the other thing about individuals of African descent is that they have a lot of genetic diversity. The most amount of genetic diversity is found within individuals of African descent across Africa than anywhere else in the world.

MA: Could you explain what elite controllers are and why there appear to be an unusual number of them in South Africa?

VR: So, elite controllers are individuals infected with HIV that do not take antiretroviral therapy, but they have very low levels of the virus. When we measure the virus within these individuals and calculate the viral load so the viral load is how much of virus is present within the person at a time we notice that in these individuals have a very, very low viral  load despite not taking any antiretroviral therapy.

We assume that these individuals are being able to protect themselves against disease progression by some sort of mechanisms that's unique to their body so we think that the human genetics that are present within these individuals give them some sort of protection against disease progression.

Elite controllers are found at higher levels in South Africa simply because we have more HIV infected individuals in South Africa than other countries around the world. We have approximately 7.8 million people infected with HIV in South Africa. Because elite controllers are found at less than 1% of HIV-positive individuals, because of the sheer number of HIV infected individuals we find them in much more higher numbers in South Africa.

MA: Could you explain how the HIV Host Genome project has contributed to our understanding of elite controllers?

VR: We have sequenced the human genomes of the elite controllers within South Africa and what we found is there is a group of unique polymorphisms that are present within these individuals that associate with protection from disease progression. And this is unique because we do not see these polymorphisms in other studies. There have been studies that have been published on the Western population and Caucasians and amongst elite controllers and we noticed that our mutations that we have detected here are more unique and haven't been reported previously. So we suspect that there may be unique genetic aspects that are found within individuals of African descent that may be conferring protection against the disease pathways.

MA: Generally speaking, what are the differences between the disease progression of HIV in African populations vs, for example, Caucasian or Asian populations?

VR: Generally, the disease patterns are about the same across different ethnicities. But what we notice is that the disease patterns are much more pronounced amongst individuals of African descent because of the sheer volume of HIV infected individuals. Because we have greater numbers of HIV positive people, we can see the rare phenotypes or rare groups of individuals that are present.

For example, elite controllers are one group of individuals able to control the virus despite taking no antiretroviral therapy. Another group is individuals that can protect themselves against getting infected with the virus. Despite having repeated exposures to the virus, these individuals do not contract HIV.

In South Africa, we have observed that female sex workers can control the virus despite repeated exposure and not using condoms or other protective measures. They seem to protect themselves from infection, although the mechanisms behind this protection are not yet fully understood. Additionally, the large volume of samples available allows us to study these individuals at a much higher level than anywhere else in the world.

We were able to perform whole human genome sequencing using the MGI sequencing platform to identify new polymorphisms that are present within individuals of African descent that are associated with elite control status. Using this technology, we were able to identify novel mutations amongst individuals of African descent and link them to a specific disease outcome, such as elite control. We believe that this technology will be able to help us in the future identifying new genetic effects on various different disease outcomes.