Successful HAART Is Associated with High B-Chemokine Levels in Chronic HIV Type 1-Infected Patients

Abstract

Chemokine receptors are used by HIV-1 for entry into CD4+ T cells. The beta-chemokines are capable of inhibiting HIV replication. This study measured beta-chemokine macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels and determined the CCR5 and CXCR4 expression on T cells in HIV-1-infected patients treated with HAART. The time of known HIV infection and time of HAART use were similar between failure and successful groups. The CD4+ T cell nadir was 163 vs. 251 cells/mm3, p = 0.07, for failure and successful groups, respectively. The successfully treated group, when compared with the failure group, had a higher median CD4+ T cells count (667 vs. 257 cells/mm3; p = 0.003) as well as higher spontaneous MIP-1alpha (median of 4390 vs. 802 pg/ml, p = 0.03) and MIP-1beta (median of 2416 vs. 1117 pg/ml, p = 0.001) levels. The untreated patients had a higher number and intensity of CCR5- and CXCR4-expressing T cells. Higher levels of chemokines were not related to nadir CD4+ T and current CD8+ T cell counts. Successfully treated patients were able to produce higher amounts of beta-chemokines and normalize the coreceptor overexpression on T cells. These findings may have clinical implications, such as a new strategy of using chemokines as adjuvants in anti-HIV therapy.

Chemokine Receptors Expression on T Cells and Response to HAART Among Chronic HIV-1-Infected Subjects

“…These results also indicate that patients on therapeutic success had increased -chemokines, what may have clinical implications [14]. Indeed, the antagonists of the CCR5 coreceptor are being developed as the first anti-HIV agents that act in the target cells of the host, and are currently under study in clinical stage [19].…”

“…These findings indicate that the replication induced increasing expression of these receptors. In fact, after successful HAART, the CCR5 and CXCR4 expression, as well the production of beta-chemokines, was modified [14], what may reflect the peripheral memory or naïve T cells redistribution and/or decreasing immune activation [15,16]. These modifications on molecules involved on viral tropism and anti-HIV activity may contribute to the emergence of virus variants when HAART fails.…”

High MIP-1β Levels in Plasma Predict Long-Term Immunological Nonresponse to Suppressive Antiretroviral Therapy in HIV Infection

“…With its cognate receptor being the HIV co-receptor CCR5, it also has HIV-suppressive properties, at least in vitro, by blocking the receptor and promoting its internalisation [142,143]. Furthermore, the capacity of CD8 + T cells to secrete large amounts of MIP-1β on stimulation has been linked with HIV controller status and full viral suppression on ART [144,145]. However, the in vivo significance of MIP-1β in HIV infection is still unclear, not least because T cells may not be the principal cellular source of plasma MIP-1β.…”

Whole blood assessment of antigen specific cellular immune response by real time quantitative PCR: a versatile monitoring and discovery tool

“…Our data document for the first time that in vaccinated individuals the capability to express MIP-1β (CCL4) gene in response to HBsAg is highly significantly correlated with specific antibody titers. Indeed, this chemokine has been suggested to play an important role in antiviral defense, either by direct mechanisms or following the activation of cells presenting viral antigens to T cells [ 25 - 28 ].…”