Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

Abstract

BackgroundCytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy.Methodology/Principal FindingsWe analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio.Conclusion/SignificanceWith these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse.

Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals

“…Consistent with elevated IFN- γ levels, higher IFN- γ to IL-10 and IFN- γ to adiponectin ratios were observed in the TB cases. These findings are, in part, consistent with previous studies showing higher IFN- γ to IL-10 ratio among antitubercular drug sensitive mycobacteria infected patients and newly diagnosed HIV and TB coinfected individuals [ 7 , 11 ]. Since host immune responses are dependent on the bacterial load [ 41 ], we theorize that the higher ratios of IFN- γ to IL-10 and IFN- γ to adiponectin mirror upregulation of proinflammatory cytokine response in early stage mycobacterial infection.…”

“…Since host immune responses are dependent on the bacterial load [ 41 ], we theorize that the higher ratios of IFN- γ to IL-10 and IFN- γ to adiponectin mirror upregulation of proinflammatory cytokine response in early stage mycobacterial infection. This proposition is supported by previous studies reporting that higher IFN- γ to IL-10 ratio is associated with hyperinflammation leading to disease severity in newly diagnosed HIV and TB coinfected patients [ 7 , 10 ]. In addition, adiponectin inhibits bacterial lipopolysaccharide-induced production of proinflammatory cytokines suppressing macrophage mycobactericidal effects [ 42 ].…”

“…In contrast, increased plasma IL-10 levels in the presence of lower concentrations of IFN- γ were detected in chronic TB patients [ 5 ]. In addition, previous studies showed a higher IFN- γ to IL-10 ratio in treatment-naive newly infected TB patients [ 6 , 7 ], suggesting that M. tuberculosis infections are characterised by an early burst in the proinflammatory cytokine response followed by an increased anti-inflammatory cytokine response in the chronic phases of disease.…”

Mycobacterial and HIV Infections Up-Regulated Human Zinc Finger Protein 134, a Novel Positive Regulator of HIV-1 LTR Activity and Viral Propagation

“…The impact of HIV-1 and mycobacterial infections on the expression of hZNF-134 was studied in PBMCs and the observations were substantiated by using tuberculosis patient samples. With this study, we propose that up-regulation of hZNF-134 by mycobacteria may be one of the molecular mechanisms explaining the high HIV-1 titers observed during HIV-TB co-infections [4], [36]. We also put forward that the uncharacterized host protein of undeciphered function in the host, assumes a novel regulatory role during host-pathogen interaction.…”

NEOPTERIN AND CD4+ T-LYMPHOCYTES IN STAGE I HIV INFECTION (Neopterin dan Limfosit T-CD4+ di Infeksi HIV Stadium I)

“…Both tests are expensive and require skilled health personnel, therefore an alternative parameter is acquired, in order to reduce the economic burden of developing countries. [1][2][3][4] The alternative test is expected to be cheaper and can be used to monitor the progress of the disease as well as the response of the HIVinfected treatment. Changes in neopterin concentration occurred earlier than the decrease in the number of CD4 + T-lymphocytes and the clinical progress of the disease, therefore the treatment could be used to predict further development towards AIDS.…”