4 research outputs found
Differential localization and limited cytotoxic potential of duodenal CD8+Tcells
- Author
- Publication venue
- 'American Society for Clinical Investigation'
- Publication date
- 08/02/2022
- Field of study
The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8(+) T cells. The role of duodenal Trm CD8(+) T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8(+) T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69(+)CD103(hi)) cells were the predominant CD8(+) T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that CD103(+)CD8(+) T cells were localized in the intraepithelial region, while CD103(â)CD8(+) T cells and CD4(+) T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8(+) T cells were enriched in the CD69(+)CD103(â/lo) population. However, the duodenal HIV-specific CD8(+) Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that duodenal CD8(+) Trm cells possess limited perforin-mediated cytolytic potential and are spatially separated from HIV-susceptible LP CD4(+) T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies
East and Central Africa
- Author
- A. Calder
- A.A. Mazrui
- A.A. Mazrui
- A.A.Mazrui
- A.J. Gurr
- A.M. Selim
- Adhero Isaac.
- Amatesha A.D.
- Angira Jared.
- Atieno-Odhiambo
- B. Tejani
- B. Tejani
- Bosco Peter John.
- Byabanazima Victor.
- C.L.Wanjala.
- C.N. Okumu
- Chahilu B.
- Chris L. Wanjala
- D.Imbuga
- D.Pownall
- D.S.Ahlander
- E. Gachukia
- E. Kezilahabi
- E.D. Jones
- Ejughemre
- F.M. Topan
- J. Angira
- J. de Graft
- J. Jahn
- J. Jahn
- J. Jahn
- J. Jahn
- J. Karioki
- J. Knappert
- Kantai O.
- Karanja Mugambi.
- Kassam Amin.
- Kayura Legson.
- Kibera Leonard.
- Kiiru Muchugu.
- Komolo Ejiet.
- Lipenga Ken.
- Lo Gune Zama Duku.
- Lo Liyong Taban.
- M. Etherton
- M. Macpherson
- Mangua Charles.
- Mazrui Ali A.
- Mbele Joe
- Mbele Joe.
- Mulwa David K.
- Namalomba Anthony.
- Nazareth Peter.
- Ngugi wa Thiong'o
- Ngugi wa Thiong'o.
- Ngugi Njoroge.
- Nkosi Leonard C.
- Okot p'Bitek
- Okoye Gilbert Shylock.
- Osotsi W.
- p'Bitek Okot.
- P. Simoko
- P.Nazareth
- Palangyo Peter.
- Phwitiko Eliot.
- R. Kagia
- R. Sander
- S. Chimombo
- S. Muteka
- S. Soile
- Ssaali Michael Joseph.
- Wamai J.G.
- Watene Kenneth.
- Were Miriam.
- Zirimu E.N.
- Publication venue
- 'SAGE Publications'
- Publication date
- Field of study
The Unaddressed Needs of Alcohol-Using Couples on Antiretroviral Therapy in Malawi: Formative Research on Multilevel Interventions
- Author
- A Conroy
- A Kagee
- A Leddy
- A Levitt
- AA Conroy
- AA Conroy
- AA Conroy
- AA Conroy
- AA Conroy
- AA Conroy
- AJ Rogers
- Allison Ruark
- AM Minnis
- Amy A. Conroy
- B Wandera
- BR Karney
- C Rusbult
- CS Hendershot
- D Baliunas
- D Umberson
- EF Kaner
- ES Wu
- G Chang
- G Wagner
- IS Speizer
- JA Hahn
- James Mkandawire
- JH Samet
- JM Turan
- Judith A. Hahn
- Judy Y. Tan
- JY Tan
- K Bush
- KC Klostermann
- KE Leonard
- KJ Karriker-Jaffe
- L Spencer
- LA Darbes
- LA Scott-Sheldon
- LA Scott-Sheldon
- LM Rodriguez
- Lynae A. Darbes
- M Arrivillaga
- M Swann
- MA Lewis
- MA Lewis
- MN Christoffersen
- MP Marshal
- P Bachanas
- PA Shuper
- R Sundararajan
- R Velleman
- RH Remien
- RK Papas
- RK Papas
- RM Senyonyi
- RS Braithwaite
- S Barve
- S Nkosi
- SC Kalichman
- SC Kalichman
- SD Weiser
- SE Woolf-King
- SL Dworkin
- Stacey A. McKenna
- TJ Oâfarrell
- U Brofenbrenner
- W Fals-Stewart
- W Fals-Stewart
- WM Wechsberg
- WM Wechsberg
- World Health Organization
- Z Eisikovits
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial
- Author
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- Abdallah J
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- Publication venue
- 'International AIDS Society'
- Publication date
- 01/01/2016
- Field of study
Meeting abstract FRAB0101LB from 21st International AIDS Conference 18â22 July 2016, Durban, South Africa.
Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIVâinfected adults and children with advanced disease in subâSaharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown.
Methods:
The REALITY 2Ă2Ă2 factorial openâlabel trial (ISRCTN43622374) randomized ARTânaĂŻve HIVâinfected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (antiâtuberculosis) and fluconazole (antiâcryptococcal/candida), 5 days azithromycin (antiâbacterial/protozoal) and singleâdose albendazole (antiâhelminth)), versus standardâofâcare cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixedâdose combination. Two other randomizations investigated 12âweek adjunctive raltegravir or supplementary food. The primary endpoint was 24âweek mortality.
Results:
1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% lossâtoâfollowâup). Median baseline CD4 was 36 cells/mm3 (IQR: 16â62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54â0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58â0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2).
Conclusions:
Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIVâinfected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this lowâcost broad infection prevention package which could save 3.3 lives for every 100 individuals treated