Dataset Information

Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals.

ABSTRACT: We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investigated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment containing inducible replication competent virus in treated aviremic HIV-infected individuals.

SUBMITTER: Banga R

PROVIDER: S-EPMC5807378 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Blood CXCR3<sup>+</sup> CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals.

Banga Riddhima R Procopio Francesco A FA Ruggiero Alessandra A Noto Alessandra A Ohmiti Khalid K Cavassini Matthias M Corpataux Jean-Marc JM Paxton William A WA Pollakis Georgios G Perreau Matthieu M

Frontiers in immunology 20180205

We recently demonstrated that lymph nodes (LNs) PD-1<sup>+</sup>/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribut ...[more]

PMID: 29459864

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Project description:Although antiretroviral therapy (ART) effectively suppresses HIV replication, the latent reservoir remains the barrier to HIV eradication. It remains unknown whether long-term ART impacts levels of inducible replication-competent provirus. To address this knowledge gap, we assessed the proviral reservoir in HIV-1 perinatally infected adolescents having received ART for >13 years. We recruited 15 vertically infected adolescents living with HIV in Botswana. Historical viral load, CD4+ T cell count, and treatment data were retrieved from their outpatient medical records. Inducible replication-competent proviruses from cryopreserved peripheral blood mononuclear cells were quantified using a TZM-bl based assay (TZA). Total proviral DNA copies were quantified using droplet digital PCR. The mean age of study participants was 16 years (standard deviation = 0.7) and median CD4+ T cell count at enrollment was 784 [interquartile range (IQR) = 728.8-1,288] cells/mm3. Median age at ART initiation was 8 (IQR = 6-12) months. Fourteen (93%) participants had HIV-1 RNA <400 copies/mL at the time of enrollment in the study. A median of 19 (IQR = 18-27) HIV-1 RNA measurements were available per participant. Six (40%) participants displayed viral suppression at all clinic visits since initiating ART, whereas the remaining 9 (60%) had one or more clinic visits with detectable HIV-1 RNA. The median inducible replication-competent provirus count was 7.4 infectious units per million cells (IQR = 6.7-19.2), and did not differ significantly by either complete or incomplete viral suppression (7.2 vs. 7.4, p = .86), or by age at ART initiation (7.4 if <12 months, 11.2 if >12 months, p = .85). The median total HIV DNA count was 129.1 copies per million cells (IQR = 18.9-212.3). Our data suggest that long-term ART initiated within the 1st year in perinatally infected infants did not eliminate proviral DNA or inducible replication-competent proviruses.

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Dataset Information

Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals.

Publications

Blood CXCR3<sup>+</sup> CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals.

Similar Datasets

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