Case report: mechanisms of HIV elite control in two African women
Abstract Background 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 individu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12879-018-2961-8 |
| _version_ | 1818307638036791296 |
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| author | Yumna Moosa Ramla F. Tanko Veron Ramsuran Ravesh Singh Mashudu Madzivhandila Nonhlanhla Yende-Zuma Melissa-Rose Abrahams Philippe Selhorst Kamini Gounder Penny L. Moore Carolyn Williamson Salim S. Abdool Karim Nigel J. Garrett Wendy A. Burgers |
| author_facet | Yumna Moosa Ramla F. Tanko Veron Ramsuran Ravesh Singh Mashudu Madzivhandila Nonhlanhla Yende-Zuma Melissa-Rose Abrahams Philippe Selhorst Kamini Gounder Penny L. Moore Carolyn Williamson Salim S. Abdool Karim Nigel J. Garrett Wendy A. Burgers |
| author_sort | Yumna Moosa |
| collection | DOAJ |
| description | Abstract Background 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. Case presentation 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. Conclusion 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. |
| first_indexed | 2024-12-13T07:01:33Z |
| format | Article |
| id | doaj.art-2629c9832d204b99a6361f0db86fb9ed |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-13T07:01:33Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-2629c9832d204b99a6361f0db86fb9ed2022-12-21T23:55:56ZengBMCBMC Infectious Diseases1471-23342018-01-011811710.1186/s12879-018-2961-8Case report: mechanisms of HIV elite control in two African womenYumna Moosa0Ramla F. Tanko1Veron Ramsuran2Ravesh Singh3Mashudu Madzivhandila4Nonhlanhla Yende-Zuma5Melissa-Rose Abrahams6Philippe Selhorst7Kamini Gounder8Penny L. Moore9Carolyn Williamson10Salim S. Abdool Karim11Nigel J. Garrett12Wendy A. Burgers13Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-NatalInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape TownCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-NatalDepartment of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central HospitalCentre for HIV and STIs, National Institute for Communicable Diseases (NICD) of the National Health Laboratory ServiceCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-NatalInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape TownInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape TownHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-NatalCentre for HIV and STIs, National Institute for Communicable Diseases (NICD) of the National Health Laboratory ServiceCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-NatalCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-NatalCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-NatalInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape TownAbstract Background 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. Case presentation 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. Conclusion 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.http://link.springer.com/article/10.1186/s12879-018-2961-8Elite controllersHIVHost restriction factorsT-cell responses |
| spellingShingle | Yumna Moosa Ramla F. Tanko Veron Ramsuran Ravesh Singh Mashudu Madzivhandila Nonhlanhla Yende-Zuma Melissa-Rose Abrahams Philippe Selhorst Kamini Gounder Penny L. Moore Carolyn Williamson Salim S. Abdool Karim Nigel J. Garrett Wendy A. Burgers Case report: mechanisms of HIV elite control in two African women BMC Infectious Diseases Elite controllers HIV Host restriction factors T-cell responses |
| title | Case report: mechanisms of HIV elite control in two African women |
| title_full | Case report: mechanisms of HIV elite control in two African women |
| title_fullStr | Case report: mechanisms of HIV elite control in two African women |
| title_full_unstemmed | Case report: mechanisms of HIV elite control in two African women |
| title_short | Case report: mechanisms of HIV elite control in two African women |
| title_sort | case report mechanisms of hiv elite control in two african women |
| topic | Elite controllers HIV Host restriction factors T-cell responses |
| url | http://link.springer.com/article/10.1186/s12879-018-2961-8 |
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