Impaired CD4+ T-Cell Restoration in the Small Versus Large Intestine of HIV-1–Positive South Africans Receiving Combination Antiretroviral Therapy

Cassol, Edana; Malfeld, Susan; Mahasha, Phetole Walter; Bond, Robert P.; Slavík, Tomáš; Seebregts, Christopher J.; Poli, Guido; Cassol, Sharon; Merwe, Schalk van der; Rossouw, Theresa M.

doi:10.1093/infdis/jit249

Cited by 21 publications

(18 citation statements)

References 44 publications

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“…Similarly, the ratio of the mean CD4% in HIV+ to HIV- individuals (HIV+/HIV-) was considerably greater in rectum than either ileum or blood, suggesting less depletion or greater reconstitution in the rectum. This finding is supported by prior studies suggesting greater CCR5+CD4+T cell depletion in the ileum compared to colon[ 22 ], less restoration in the duodenum compared to colon[ 25 ], and possible restoration of normal CD4% in the rectum[ 17 ].…”

Section: Discussionsupporting

confidence: 81%

“…Little is known about the normal variation in T cell numbers and phenotypes throughout the GI tract [ 18 ]. Relatively few studies in treated HIV+ patients have examined more than one gut site [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ], and few of these have included HIV- individuals[ 21 , 22 , 24 ]. In one study of ART-treated HIV+ patients, HIV levels and T cell frequencies varied significantly across the gut, with the ileum having the highest HIV transcriptional activity (RNA/DNA) and the rectum having the highest HIV DNA and CD4+T cell frequency[ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Site-Specific Differences in T Cell Frequencies and Phenotypes in the Blood and Gut of HIV-Uninfected and ART-Treated HIV+ Adults

et al. 2015

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Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Site-Specific Differences in T Cell Frequencies and Phenotypes in the Blood and Gut of HIV-Uninfected and ART-Treated HIV+ Adults

et al. 2015

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“…An association between impaired mucosal CD4 þ T-cell reconstitution and non-specific enteritis has recently been described. 23 Moreover, evidence for increased incidence of adenomas and intestinal malignancies in treated chronically HIV-infected patients 38,39 suggests that mucosal immune defects increase the risk of adverse outcome despite otherwise effective long-term cART. Our findings of increased systemic immune activation and enterocyte damage indicate ongoing inflammatory disease progression in treated patients with persistent mucosal CD4 þ T-cell depletion.…”

Section: Discussionmentioning

confidence: 99%

“…22 Although these observations emphasize the need for extensive quantitative studies, published data on absolute numbers of mucosal T cells in the context of HIV infection are sparse. [21][22][23] Therefore, we conducted a quantitative analysis of mucosal CD4 þ T cells in untreated and treated patients at different stages of HIV disease in comparison to HIV-uninfected control subjects.…”

Section: Introductionmentioning

confidence: 99%

The effect of timing of antiretroviral therapy on CD4+ T-cell reconstitution in the intestine of HIV-infected patients

et al. 2016

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Whether and to what extent gut mucosal CD4(+) T cells of HIV-infected patients can be restored by combination antiretroviral therapy (cART) is not yet fully resolved. We studied absolute numbers, differentiation, and activation of mucosal CD4(+) T cells at different stages of HIV infection and assessed the effect of timing of cART initiation on this cell population. Mucosal CD4(+) T-cell numbers were severely reduced at all stages of chronic infection, but normal in patients with acute infection. In patients with initiation of cART during chronic HIV infection, mucosal CD4(+) T cells restored to less than half of the numbers in controls. However, in patients who initiated cART during acute HIV infection, mucosal CD4(+) T-cell numbers were fully preserved and markers of microbial translocation and inflammation reversed to normal. The proportion of mucosal effector memory CD4(+) T cells normalized only if cART was initiated at >350 CD4(+) T cells per μl blood but not with delayed treatment. In conclusion, mucosal CD4(+) T-cell numbers can be preserved if cART is initiated in acute HIV infection. In chronically HIV-infected patients, early cART improves mucosal CD4(+) T-cell differentiation but cannot prevent the persistent lack of total CD4(+) T cells.

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“…No entanto, sabe-se que a manutenção do estado imunológico está associada a um conjunto de fatores e que a baixa contagem de células CD4 pode ser preditiva de piora no prognóstico da doença. (20) Doenças oportunistas em indivíduos com HIV se desenvolvem em decorrência da imunodeficiência do hospedeiro. Ou seja, quanto menor for a contagem de linfócitos T CD4, maior será a imunodeficiência do indivíduo com HIV e maior será a chance de desenvolver algum tipo de doença oportunista.…”

Section: Discussionunclassified

Evaluation of oxidative status, food consumption of zinc and plasma zinc in HIV-infected individuals

Tonel¹,

Silva²,

Maziero³

et al. 2018

Revista Brasileira De Análises Clínicas

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Artigo Original/Original Article Resumo Objetivo: Objetivou-se analisar o consumo alimentar e os níveis plasmáticos de zinco além de biomarcadores do status oxidativo de pacientes com infecção pelo HIV. Métodos: Foram selecionados indivíduos adultos com HIV e contagem de linfócitos T CD4<500 células/mm 3 , assistidos por um centro especializado, localizado na região oeste do Paraná. Realizou-se a aplicação de questionários, avaliação antropométrica e coleta sanguínea para análise de zinco e biomarcadores do status oxidativo. Resultados: Avaliou-se um total de quarenta indivíduos adultos, nos quais se observaram consumo adequado de zinco e grande frequência de eutrofia e sobrepeso. Obteve-se correlação positiva entre tióis proteicos (SH-P) e os níveis plasmáticos de zinco e correlação negativa entre SH-P e a peroxidação lipídica (PL) no plasma e nos eritrócitos. Além disso, verificou-se um aumento nos níveis de SH-P em pacientes com presença de doença oportunista em alguma fase da infecção viral. Conclusão: Apesar de não ter sido observada relação entre níveis de zinco sanguíneo e a contagem de linfócitos T CD4 e carga viral, as propriedades do mineral ainda são defendidas como essenciais.

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Impaired CD4+ T-Cell Restoration in the Small Versus Large Intestine of HIV-1–Positive South Africans Receiving Combination Antiretroviral Therapy

Abstract: Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4(+) T-cell recovery and improve therapeutic outcomes.

Cited by 21 publications

References 44 publications

Site-Specific Differences in T Cell Frequencies and Phenotypes in the Blood and Gut of HIV-Uninfected and ART-Treated HIV+ Adults

Site-Specific Differences in T Cell Frequencies and Phenotypes in the Blood and Gut of HIV-Uninfected and ART-Treated HIV+ Adults

The effect of timing of antiretroviral therapy on CD4+ T-cell reconstitution in the intestine of HIV-infected patients

Evaluation of oxidative status, food consumption of zinc and plasma zinc in HIV-infected individuals

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