DESIGN: Antiretroviral therapy (ART) currently represents the best way to avert the lethal consequences of chronic persistent HIV-1 infection. It leads to significant reductions of plasma viremia, often to undetectable levels, but it can also be linked with the reduction and disappearance of detectable HIV-specific CD8 T-cell responses. RESULTS: Here we describe a group of patients in whom ongoing replication of HIV, particularly transcription of Nef mRNA species, was detected despite prolonged and clinically successful antiretroviral treatment. Modest, but significant, numbers of HIV-specific CD8 T cells and CD4 T-cell responses were found in these subjects, with the strongest responses directed towards Nef epitopes. Detailed phenotypic analysis of the HIV-specific CD8 cells demonstrated low perforin levels and persistent expression of CD27, a phenotype associated with incomplete differentiation of cytotoxic T lymphocytes (CTL). CONCLUSION: This immature CTL phenotype has been described previously in association with chronic HIV disease, but its continued persistence is surprising in the setting of prolonged viral suppression on therapy and the presence of HIV-specific CD4 cell activity.
DESIGN: Antiretroviral therapy (ART) currently represents the best way to avert the lethal consequences of chronic persistent HIV-1 infection. It leads to significant reductions of plasma viremia, often to undetectable levels, but it can also be linked with the reduction and disappearance of detectable HIV-specific CD8 T-cell responses. RESULTS: Here we describe a group of patients in whom ongoing replication of HIV, particularly transcription of Nef mRNA species, was detected despite prolonged and clinically successful antiretroviral treatment. Modest, but significant, numbers of HIV-specific CD8 T cells and CD4 T-cell responses were found in these subjects, with the strongest responses directed towards Nef epitopes. Detailed phenotypic analysis of the HIV-specific CD8 cells demonstrated low perforin levels and persistent expression of CD27, a phenotype associated with incomplete differentiation of cytotoxic T lymphocytes (CTL). CONCLUSION: This immature CTL phenotype has been described previously in association with chronic HIV disease, but its continued persistence is surprising in the setting of prolonged viral suppression on therapy and the presence of HIV-specific CD4 cell activity.
Authors: L Papagno; V Appay; J Sutton; T Rostron; G M A Gillespie; G S Ogg; A King; A T Makadzanhge; A Waters; C Balotta; A Vyakarnam; P J Easterbrook; S L Rowland-Jones Journal: Clin Exp Immunol Date: 2002-12 Impact factor: 4.330
Authors: Afam A Okoye; Derick D Duell; Yoshinori Fukazawa; Benjamin Varco-Merth; Alejandra Marenco; Hannah Behrens; Morgan Chaunzwa; Andrea N Selseth; Roxanne M Gilbride; Jason Shao; Paul T Edlefsen; Romas Geleziunas; Mykola Pinkevych; Miles P Davenport; Kathleen Busman-Sahay; Michael Nekorchuk; Haesun Park; Jeremy Smedley; Michael K Axthelm; Jacob D Estes; Scott G Hansen; Brandon F Keele; Jeffery D Lifson; Louis J Picker Journal: J Clin Invest Date: 2021-04-15 Impact factor: 14.808
Authors: Chris Y Chiu; Judy J Chang; Ashanti I Dantanarayana; Ajantha Solomon; Vanessa A Evans; Rachel Pascoe; Céline Gubser; Lydie Trautman; Rémi Fromentin; Nicolas Chomont; James H McMahon; Paul U Cameron; Thomas A Rasmussen; Sharon R Lewin Journal: J Immunol Date: 2021-12-01 Impact factor: 5.422
Authors: Adam J Ritchie; Suzanne L Campion; Jakub Kopycinski; Zoe Moodie; Z Maggie Wang; Kruti Pandya; Stephen Moore; Michael K P Liu; Simon Brackenridge; Kristin Kuldanek; Kenneth Legg; Myron S Cohen; Eric L Delwart; Barton F Haynes; Sarah Fidler; Andrew J McMichael; Nilu Goonetilleke Journal: J Virol Date: 2011-01-26 Impact factor: 5.103
Authors: Jennifer Serwanga; Susan Mugaba; Auma Betty; Edward Pimego; Sarah Walker; Paula Munderi; Charles Gilks; Frances Gotch; Heiner Grosskurth; Pontiano Kaleebu Journal: AIDS Res Treat Date: 2011-01-18
Authors: Michael A Eller; Bonnie M Slike; Josephine H Cox; Emil Lesho; Zhining Wang; Jeffrey R Currier; Janice M Darden; Victoria R Polonis; Maryanne T Vahey; Sheila Peel; Merlin L Robb; Nelson L Michael; Mary A Marovich Journal: PLoS One Date: 2011-09-16 Impact factor: 3.240