HIV infection is a chronic infection that almost inevitably progresses to AIDS. The infection is characterized by the deterioration in the immune function leading to opportunistic infections and malignancies. Additionally, there is an associated immune dysfunction characterized by a persistent inflammatory state and unhealthy elaboration of both pro- and anti-inflammatory cytokines. The CD4+ T cell count has been used as a surrogate for the level of immune dysfunction that exists in patients with HIV infection. Eighty-eight (88) patients with HIV infection, forty-four (44) of whom were treatment naïve patients and forty-four (44) who were treatment-experienced patients, were recruited. The serum concentrations of cytokines IL-6 and IL-10 were carried out using R&D human
The human immunodeficiency virus type-1 (HIV-1) infection and its sequelae, the acquired immune deficiency syndrome (AIDS), are the major causes of morbidity and mortality worldwide, accounting for over 35 million deaths since the first reported cases in 1983 [
Cytokines are a group of low molecular weight proteins that mediate communication between immune system cells. They contribute to chemical signaling pathways that regulate cell development, tissue repair, haematopoiesis, inflammation, and immune responses. They act in a complex network where one cytokine can influence the production of, and response to, many other cytokines [
The CD4 T lymphocytes, also called T helper cells, are important in the coordination of the immune system by directing immune responses against pathogens either towards a predominantly humoral or a cell-mediated response depending on the nature of the antigen and the immune receptor that has been activated by the antigen. Additionally, subsets of the T helper cells are crucial in the regulation of immune responses in immunocompetent individuals. By selectively targeting the CD4+ T cell, infection with HIV not only renders an immunodeficient individual but also produces a state of immune disarray which manifests as a clinical predisposition to infections and a persistent inflammatory state which has been demonstrated even in individuals who are on cART and who have had virological suppression with viral suppression below detected serum levels.
Improvement of patients with HIV is documented clinically by the improvements in clinical conditions, virologically by the reductions in HIV RNA viral loads, and immunologically by the CD4+ T cell count. For long, clinical decisions in HIV-infected individuals have been based on the CD4+ T cell counts of such individuals, but questions remain as to how well the peripheral CD4+ T cell count mirrors the true state of the immune dysfunction seen in patients who have been infected with HIV.
The aim of this study was therefore to assess the relationship between the CD4+ T cell count and the serum levels of IL-6 and IL-10 in patients infected with HIV whether on treatment or not, who were attending the ART clinic of the Ahmadu Bello University Teaching Hospital, Shika-Zaria.
This study was carried out in the outpatient clinic of the Ahmadu Bello University Teaching Hospital (ABUTH) HIV program. The HIV program is situated in the NASARA complex and is part of the 700-bed referral hospital located in Shika-Zaria, Kaduna State. Eighty-eight (88) patients were selected consecutively. They included forty-four (44) newly diagnosed ART- (antiretroviral treatment-) naïve patients to comprise the test group and another forty-four (44) ART-experienced patients to serve as the comparison group. The comparison group included patients who had been receiving ARTs for at least 6 months. All eighty-eight samples (88) had IL-6 and IL-10 assays carried out on them, as well as CD4+ T cell enumeration.
The study was a comparative cross-sectional study. Ethical approval for the study was obtained from the ABUTH Ethical and Scientific committee. Adequate counseling and informed consent were applied confidentially throughout the course of the research. Data was collected using a researcher-administered questionnaire, which captured the biodata/sociodemographic characteristics, medical history, and the physical examination of the participants.
The levels of both serum IL-6 and IL-10 were assayed using the
All data was analyzed using Statistical Package for the Social Sciences (SPSS), version 20.0, Chicago, IL, USA. Qualitative variables were reported as percentages. Normally distributed quantitative variables (e.g., age) were presented as mean and standard deviation, while those with uneven distribution (e.g., CD4 count and cytokine levels) were presented as median and range. Statistical test of significance was set at 5% alpha level using the chi-square and Pearson’s correlation for qualitative and quantitative variables, respectively. The Student
Males constituted 54.5% (48) of the study participants while 45.5% (40) were female. The mean age in the study was 36.6 ± 8.8 years, and the majority of the respondents were of the Hausa/Fulani extraction, constituting 51% (45) of the participants. Participants of Ibo and Yoruba extraction each constituted 4.5% (4) of the respondents.
The median serum interleukin-6 concentration was lower among the female participants compared to the male counterparts, with median values of 3.74 pg/mL (0.00–171.00 pg/mL) and 2.36 pg/mL (0.00–45.31 pg/mL) among the male and female participants, respectively (
The median CD4+ T cell count in the ART-naïve group was 166 cells/
Immunological parameters of participants.
Parameter | ART naïve | ART experienced |
|
---|---|---|---|
Median† CD4 concentration | 166 cells/ |
463 cells/ |
< |
Median IL-6 concentration | 6.8 pg/mL (1.2–316) | 1.4 pg/mL (1.0–27.5) | < |
Median IL-10 concentration | 10.1 pg/mL (2.1–870) | 6.0 pg/mL (3.0–39.9) |
|
The association between the patient categories (i.e., ART naïve versus ART experienced) and serum interleukin-6 levels was not affected after adjustment for the gender of the participants, with the regression coefficient for patient category reducing by 0.13% (
Both the serum IL-6 (
Median concentration of interleukins according to the WHO clinical stage of HIV.
WHO clinical stage | IL-6 concentration (pg/mL) | IL-10 concentration (pg/mL) |
---|---|---|
1 | 2.22 (0.00–37.97) |
10.15 (0.00–47.37) |
2 | 2.22 (0.00–45.31) | 26.32 (5.64–43.23) |
3 | 7.76 (1.39–65.13) | 30.83 (12.40–48.50) |
4 | 171.00 (4.70–175.84) | 134.20 (14.66–800.00) |
There was no significant increase of interleukin-6 levels with the WHO clinical stage II of HIV compared to stage I (
As shown above, there was a significant difference in the median serum concentrations of IL-6 among the study categories of patients, with levels significantly higher among the treatment-naïve subjects compared to the ART-experienced subjects (
The IL-6 levels were affected by the ARV regimen the patient was currently taking, with the highest levels found in participants who were not on any medications and the lowest levels among those who were taking Tenofovir/Lamivudine/Efavirenz combination (1.45 pg/mL,
The levels of IL-6 were affected by the stage of treatment, with the highest levels detected among those yet to commence medications, followed by those on the 2nd line drugs (2.22 pg/mL,
Antiretroviral stage of treatment based on the sex of the participants.
ARV category | Male | Female | Total |
---|---|---|---|
ART naïve | 26 | 18 | 44 |
1st line regimen | 18 | 16 | 34 |
2nd line regimen | 4 | 6 | 10 |
There was a significant negative correlation between the duration from diagnosis to time of study and the levels of interleukin-6 (
This study showed higher interleukin levels among patients with lower CD4+ T cell counts, which is consistent with more pronounced inflammation in subjects with more advanced disease. These findings are also consistent with similar studies done elsewhere [
The findings in this study suggest that participants on Tenofovir/Emtricitabine/Efavirenz and Tenofovir/Lamivudine/Efavirenz combinations had lower levels of both interleukin-6 and interleukin-10, with higher levels observed among participants who were on Zidovudine/Lamivudine/Nevirapine combination and the protease inhibitor-containing regimens. This is in contrast to findings by workers elsewhere that suggest the suppression of interleukin levels was without respect to the ART regimen used [
Patients who had a longer duration between diagnosis and the conduct of this study were observed to have lower interleukin levels. Whether this observation is due to a more sustained viral suppression is uncertain as we did not assay for HIV viral load in our participants.
There are higher concentrations of IL-6 and IL-10 levels among HIV patients that are not on HAART, and the levels of IL-6 and IL-10 are reduced by HAART. There is a higher level of IL-6 and IL-10 among HIV patients with low CD4+ T cell counts and advanced WHO clinical stage, which was not affected by the gender of the participants. This relationship between interleukin-6 and interleukin-10 suggests that there may be a role for the use of cytokine measurements in the staging of HIV infections and this may be very useful in the setting of poor immune reconstitution with poor CD4 T lymphocyte response which is not uncommon in resource poor settings, partly on account of a severely damaged lymphoid system due to late commencement of ARVs.
The authors declare that there is no conflict of interest regarding the publication of this paper.
The authors wish to thank the management of Ahmadu Bello University for the logistic and laboratory support in the course of this study.