The online version of this article (https://doi.org/10.1186/s12879-018-2961-8) contains supplementary material, which is available to authorized users.
The majority of people living with HIV require antiretroviral therapy (ART) for controlling viral replication, however there are rare HIV controllers who spontaneously and durably control HIV in the absence of treatment. Understanding what mediates viral control in these individuals has provided us with insights into the immune mechanisms that may be important to induce for a vaccine or functional cure for HIV. To date, few African elite controllers from high incidence settings have been described. We identified virological controllers from the CAPRISA 002 cohort of HIV-1 subtype C infected women in KwaZulu Natal, South Africa, two (1%) of whom were elite controllers. We examined the genetic, clinical, immunological and virological characteristics of these two elite HIV controllers in detail, to determine whether they exhibit features of putative viral control similar to those described for elite controllers reported in the literature.
In this case report, we present clinical features, CD4+ T cell and viral load trajectories for two African women over 7 years of HIV infection. Viral load became undetectable 10 months after HIV infection in Elite Controller 1 (EC1), and after 6 weeks in Elite Controller 2 (EC2), and remained undetectable for the duration of follow-up, in the absence of ART. Both elite controllers expressed multiple HLA Class I and II haplotypes previously associated with slower disease progression (HLA-A*74:01, HLA-B*44:03, HLA-B*81:01, HLA-B*57:03, HLA-DRB1*13). Fitness assays revealed that both women were infected with replication competent viruses, and both expressed higher mRNA levels of p21, a host restriction factor associated with viral control. HIV-specific T cell responses were examined using flow cytometry. EC1 mounted high frequency HIV-specific CD8+ T cell responses, including a B*81:01-restricted Gag TL9 response. Unusually, EC2 had evidence of pre-infection HIV-specific CD4+ T cell responses.
We identified some features typical of elite controllers, including high magnitude HIV-specific responses and beneficial HLA. In addition, we made the atypical finding of pre-infection HIV-specific immunity in one elite controller, that may have contributed to very early viral control. This report highlights the importance of studying HIV controllers in high incidence settings.
Additional file 1: Figure S1-4. Figure S1. T cell activation in the CAPRISA cohorts. CD4+ and CD8+ T cell activation, as measured by the frequency of HLA-DR-positive cells. Figure S2. Flow cytometry plots of HIV-specific CD4+ responses in elite controller 2 pre- and post-infection. Figure S3. HIV neutralizing antibody responses in elite controllers. Figure S4. Host genetic factor expression in the CAPRISA cohorts. (PDF 634 kb)12879_2018_2961_MOESM1_ESM.pdf
Additional file 2: Table S1. HLA class I and II alleles identified within the elite controllers. High resolution HLA typing was performed on EC1 and EC2 and is presented in the table. (DOCX 14 kb)12879_2018_2961_MOESM2_ESM.docx
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- Case report: mechanisms of HIV elite control in two African women
Ramla F. Tanko
Penny L. Moore
Salim S. Abdool Karim
Nigel J. Garrett
Wendy A. Burgers
- BioMed Central
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