Background: The existence of HIV virological controllers shows that it is possible for the human immune system to robustly control HIV. It is hoped that a better understanding of the mechanisms of control will assist efforts to develop a functional cure. This report describes HIV controllers in an African cohort, examining their features in relation to those of their better-described counterparts in the United States and Europe.
Methods: Virological controllers were identified from a prospective seroincidence cohort of young women aged 21-33 years in KwaZulu Natal, South Africa (n = 245), and classified as either viraemic or elite controllers (ECs) according to their plasma viral load levels in the absence of antiretroviral therapy (ART). The clinical features, CD4+ T cell and viral load trends of the elite controllers were examined in more detail, and their genetic features, including HLA and KIR haplotypes, were sequenced and analysed in relation to existing published data.
Results: In the cohort there were 12 viraemic (5%) and 2 elite controllers (1%). The first EC presented post-seroconversion with multiple recurrent infections of the skin, genitourinary tract and tonsils, suggestive of some degree of immune dysfunction. The second displayed no features of HIV-associated morbidity. Both ECs showed an initial viral load spike (33 500 and 741 copies/mL respectively) but shortly thereafter achieved and maintained undetectable plasma viral loads and stable CD4+ counts (>500 cells/mm3, average 900 cells/mm3) for more than 6 years without ART. Both ECs were found to have HLA haplotypes well-described as being associated with slow progression, most notably HLA-B81* and HLA-B57* respectively. Furthermore, the first EC was found to have a KIR2DL2 subtype, also associated with slow progression.
Conclusions: While the overall subtype-C infected African cohort differed substantially from subtype-B infected cohorts in other parts of the world, the features of the African elite controllers correspond with those of their international counterparts, in terms of epidemiology, host genetics and associated immunological features. This suggests that progress in HIV controller science may be directly applicable in certain underresearched populations.