scholarly journals Regulatory T-lymphocyte subsets in patients with HIV-infection receiving highly active antiretroviral therapy

2019 ◽  
Vol 18 (1) ◽  
pp. 247-256
Author(s):  
V. A. Chereshnev ◽  
E. V. Saidakova ◽  
L. B. Korolevskaya ◽  
N. G. Shmagel ◽  
K. V. Shmagel

Background. The reason why HIV-infected patients receiving highly active antiretroviral therapy (HAART) suffer from the increased immune activation remains elusive. Regulatory T-cells (Treg) are able to control immune activation, but their quantity may vary due to the infection. The aim of this work was to estimate the number and subsets of Tregs in HIV-positive patients receiving virologically effective HAART.Materials and methods. The CD4+ T-lymphocyte (CD3+CD4+) and Treg (CD3+CD4+FOXP3+) quantities were determined by flow cytometry. Treg subsets were assessed based on the FOXP3 expression level. The state of T-cell activation was established according to the simultaneous expression of CD38 and HLA-DR molecules.Results. It was shown that HIV-positive patients compared to healthy people have reduced CD4+ T-lymphocyte counts despite virologically effective HAART. At the same time in HIV-infected people, Treg absolute numbers were only slightly decreased. Moreover, the major part of Treg pool in their blood consisted of lymphocytes with a high level of FOXP3 expression that corresponded to the phenotype of cells with the highest suppressor activity. However, an increased relative amount of activated CD4+ T-lymphocytes was retained in the HIV-infected individuals’ blood.Conclusion. In HIV-infected patients who received HAART in time and whose treatment resulted in an effective HIV viral load suppression and a satisfactory CD4+ T-cell counts increase, a relatively large pool of peripheral Tregs is maintained. However, these lymphocytes are not enough to fully control immune activation that develops against the background of chronic lentivirus infection.

2001 ◽  
Vol 8 (5) ◽  
pp. 943-948 ◽  
Author(s):  
Vesna Blazevic ◽  
Shirley Jankelevich ◽  
Seth M. Steinberg ◽  
Freda Jacobsen ◽  
Robert Yarchoan ◽  
...  

ABSTRACT The present study analyzes the effect of highly active antiretroviral therapy (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)-infected children over a 24-week period following initiation of HAART with ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included cytokine production by monocytes as well as T-cell proliferation in response to mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides. Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4+ T-cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH) response. At enrollment the children exhibited defects in several immune parameters measured. Therapy increased CD4+ T-cell counts and decreased viral loads significantly. By contrast, the only immunological parameter that was significantly increased was IL-12 p70 production by monocytes; the DTH response to Candida albicans also showed a strong increase in patients becoming positive. In conclusion, these results demonstrate that HAART in HIV-infected children affects the dynamics of HIV replication and the CD4+ T-cell count over 24 weeks, similar to the pattern seen in HIV-infected adults. Furthermore, these data indicate improvement in antigen-presenting cell immunological function in HIV-infected children induced by HAART.


2010 ◽  
Vol 84 (20) ◽  
pp. 10765-10772 ◽  
Author(s):  
Nonhlanhla N. Mkhize ◽  
Pamela P. Gumbi ◽  
Lenine J. Liebenberg ◽  
Yuan Ren ◽  
Peter Smith ◽  
...  

ABSTRACT Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hadush Negash ◽  
Haftom Legese ◽  
Mebrahtu Tefera ◽  
Fitsum Mardu ◽  
Kebede Tesfay ◽  
...  

Abstract Background Ethiopia initiated antiretroviral therapy early in 2005. Managing and detecting antiretroviral treatment response is important to monitor the effectiveness of medication and possible drug switching for low immune reconstitution. There is less recovery of CD4+ T cells among human immunodeficiency virus patients infected with tuberculosis. Hence, we aimed to assess the effect of tuberculosis and other determinant factors of immunological response among human immunodeficiency virus patients on highly active antiretroviral therapy. A retrospective follow up study was conducted from October to July 2019. A total of 393 participants were enrolled. An interviewer based questionnaire was used for data collection. Patient charts were used to extract clinical data and follow up results of the CD4+ T cell. Current CD4+ T cell counts of patients were performed. STATA 13 software was used to analyze the data. A p-value ≤0.05 was considered a statistically significant association. Results The mean age of study participants was 39.2 years (SD: + 12.2 years) with 8.32 mean years of follow up. The overall prevalence of immune reconstitution failure was 24.7% (97/393). Highest failure rate occurred within the first year of follow up time, 15.7 per 100 Person-year. Failure of CD4+ T cells reconstitution was higher among tuberculosis coinfected patients (48.8%) than mono-infected patients (13.7%). Living in an urban residence, baseline CD4+ T cell count ≤250 cells/mm3, poor treatment adherence and tuberculosis infection were significantly associated with the immunological failure. Conclusions There was a high rate of CD4+ T cells reconstitution failure among our study participants. Tuberculosis infection increased the rate of failure. Factors like low CD4+ T cell baseline count, poor adherence and urban residence were associated with the immunological failure. There should be strict monitoring of CD4+ T cell counts among individuals with tuberculosis coinfection.


AIDS ◽  
1998 ◽  
Vol 12 (16) ◽  
pp. 2115-2123 ◽  
Author(s):  
Leslie R. Bisset ◽  
Richard W. Cone ◽  
Werner Huber ◽  
Manuel Battegay ◽  
Pietro L. Vernazza ◽  
...  

Author(s):  
E. V. Saidakova ◽  
◽  
L. B. Korolevskaya ◽  
V. V. Vlasova ◽  
◽  
...  

In HIV-positive patients, hepatitis C virus (HCV) coinfection is associated with the development of se-vere systemic inflammation and an increased risk of a discordant response to highly active antiretroviral therapy in which supressed viral replication doesn’t lead to effective CD4+ T-cell regeneration. At the same time, the data on the systemic inflammation in HIV/HCV coinfected patients with ineffective resto-ration of CD4+ T-cell counts during therapy are limited. The aim of this work was to characterize system-ic inflammation in HIV/HCV coinfected patients with a discordant response to treatment. We studied three groups: 1) HIV/HCV coinfected subjects with a discordant response to therapy (CD4+ T-cells less than 350/ul); 2) HIV/HCV coinfected patients with a standard response to therapy (CD4+ T-lymphocytes over 350/ul); 3) voluntary blood donors without HIV and HCV infections. Systemic inflammation indices were assessed by the content of proinflammatory and anti-inflammatory cytokines in blood plasma (eotax-in, IL-1β, IL-4, IL-5, IL-10, IL-13, MCP-1, MIP-1α, MIP-1β, IP-10 , TNFα, TGF-β1, TGF-β2), the levels of which were analyzed by multiplex and enzyme-linked immunosorbent assays. As a result it was shown that in HIV/HCV coinfected patients, therapeutically uncontrolled hepatitis C leads to the development of pronounced systemic inflammation, which is only slightly aggravated by a discordant response to highly active antiretroviral therapy.


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