Case report: mechanisms of HIV elite control in two African women

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dc.contributor.authorMoosa, Yumna
dc.contributor.authorTanko, Ramla F
dc.contributor.authorRamsuran, Veron
dc.contributor.authorSingh, Ravesh
dc.contributor.authorMadzivhandila, Mashudu
dc.contributor.authorYende-Zuma, Nonhlanhla
dc.contributor.authorAbrahams, Melissa-Rose
dc.contributor.authorSelhorst, Philippe
dc.contributor.authorGounder, Kamini
dc.contributor.authorMoore, Penny L
dc.contributor.authorWilliamson, Carolyn
dc.contributor.authorAbdool Karim, Salim S
dc.contributor.authorGarrett, Nigel J
dc.contributor.authorBurgers, Wendy A
dc.date.accessioned2018-04-12T09:47:39Z
dc.date.available2018-04-12T09:47:39Z
dc.date.issued2018-01-25
dc.date.updated2018-04-09T15:05:04Z
dc.description.abstractBackground: 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.
dc.identifier.apacitationMoosa, Y., Tanko, R. F., Ramsuran, V., Singh, R., Madzivhandila, M., Yende-Zuma, N., ... Burgers, W. A. (2018). Case report: mechanisms of HIV elite control in two African women. <i>BMC infectious diseases</i>, http://hdl.handle.net/11427/27784en_ZA
dc.identifier.chicagocitationMoosa, Yumna, Ramla F Tanko, Veron Ramsuran, Ravesh Singh, Mashudu Madzivhandila, Nonhlanhla Yende-Zuma, Melissa-Rose Abrahams, et al "Case report: mechanisms of HIV elite control in two African women." <i>BMC infectious diseases</i> (2018) http://hdl.handle.net/11427/27784en_ZA
dc.identifier.citationMoosa, Y., Tanko, R. F., Ramsuran, V., Singh, R., Madzivhandila, M., Yende-Zuma, N., ... & Williamson, C. (2018). Case report: mechanisms of HIV elite control in two African women. BMC infectious diseases, 18(1), 54.
dc.identifier.ris TY - Journal Article AU - Moosa, Yumna AU - Tanko, Ramla F AU - Ramsuran, Veron AU - Singh, Ravesh AU - Madzivhandila, Mashudu AU - Yende-Zuma, Nonhlanhla AU - Abrahams, Melissa-Rose AU - Selhorst, Philippe AU - Gounder, Kamini AU - Moore, Penny L AU - Williamson, Carolyn AU - Abdool Karim, Salim S AU - Garrett, Nigel J AU - Burgers, Wendy A AB - 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. DA - 2018-01-25 DB - OpenUCT DO - 10.1186/s12879-018-2961-8 DP - University of Cape Town J1 - BMC infectious diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Case report: mechanisms of HIV elite control in two African women TI - Case report: mechanisms of HIV elite control in two African women UR - http://hdl.handle.net/11427/27784 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s12879-018-2961-8
dc.identifier.urihttp://hdl.handle.net/11427/27784
dc.identifier.vancouvercitationMoosa Y, Tanko RF, Ramsuran V, Singh R, Madzivhandila M, Yende-Zuma N, et al. Case report: mechanisms of HIV elite control in two African women. BMC infectious diseases. 2018; http://hdl.handle.net/11427/27784.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceBMC infectious diseases
dc.source.urihttps://bmcinfectdis.biomedcentral.com/
dc.subject.otherElite controllers
dc.subject.otherHIV
dc.subject.otherHost restriction factors
dc.subject.otherT-cell responses
dc.titleCase report: mechanisms of HIV elite control in two African women
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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