PhD Study Sheds New Light on Immune Responses that Control HIV Infection

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UKZN’s HIV Pathogenesis Programme (HPP) celebrated Dr Catherine Kegakilwe Koofhethile of Botswana obtaining a PhD in Immunology with research which has brought scientists a step closer to understanding the phenomenon whereby a rare group of individuals control HIV-1 infection without antiretroviral therapy.

Her novel study, titled: “Protective HLA Class I Alleles: Investigation of Viral Control and Lack of Control in Chronic HIV-1 Subtype C infection”, used specimens of chronically HIV-1 infected individuals in Durban. 

Koofhethile identified a subset of individuals with a genetic make-up associated with highly functional cytotoxic T cells against the HIV Gag protein. In these individuals the loss of these immune responses eventually led to high viral load and she could show that the ability of these isolated immune cells to stop virus growth in the laboratory declined as the patients’ viral load rose.

Interestingly, Koofhethile also identified a subset of individuals who appear to have alternative non-cytotoxic T cell mechanisms of viral control.  These individuals, who were also controlling HIV-1 infection without antiretroviral therapy did not have the genetic make-up associated with highly effective cytotoxic T cells and when their T cells were isolated in the laboratory, they did not stop virus growth. 

Koofhethile therefore concluded that these individuals have alternative mechanisms of achieving virus control.  She believes that these unique controllers may hold the key to an effective HIV vaccine and wants to focus her future research on understanding the novel mechanisms of HIV-1 control in these persons. 

‘During my PhD studies, I got to learn, practice and experience patience, perseverance, respect for other scientists, public speaking, dealing with constructive criticisms, sharing ideas and knowledge with others,’ said the humble graduate.

‘My research contributed to a better understanding of the mechanisms of HIV control during the chronic stage of infection and has also opened up new research questions, which are of great interest for the future vaccine design studies. We appreciate the people who are kind enough to donate their blood to us to conduct research, without whom this work would not have been possible.’

Koofhethile is now a post-doctoral Fellow at HPP under the supervision of Professor Thumbi Ndung’u and the mentorship of Dr Christina Thobakgale. ‘I am still very interested in HIV natural controllers and I hope I can unravel the puzzle and produce information that can be useful for the development of better HIV vaccines and treatment strategies,’ she said. 

Koofhethile will visit the laboratories of international collaborators, for some training to learn and equip herself with new techniques to help her develop into an independent scientist.

Koofhethile had a ‘chance of a lifetime’ opportunity to mingle with Nobel laureates recently at the 64th Lindau Nobel Laureate (Medicine and Physiology) meeting in Germany. She met the esteemed Professor Barré-Sinoussi who received a Nobel prize for her discovery of HIV.

Koofhethile said she was ecstatic to have her entire family present at her graduation – a missed opportunity when she received her BSc and master’s degrees from universities in England.

Lunga Memela