Advanced baseline immunosuppression is associated with elevated levels of plasma markers of fungal translocation and inflammation in long-term treated HIV-infected Tanzanians

Abstract

Background For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of immunosuppression during treatment initiation and the subsequent levels of inflammatory biomarkers, reservoir size and plasma marker of fungal translocation after achieving long-term virological control. Methods We analyzed 115 virally suppressed (female 83.5%) and 40 untreated (female 70%) subjects from Dar es Salaam, Tanzania. The size of HIV latent reservoir (proviral DNA copy) was determined using quantitative PCR. Inflammatory biomarkers; IL-6, IL-10, and soluble CD14 (sCD14), were measured using multiplex cytometric beads array. Antibody titers for Cytomegalovirus (CMV) and Epstein Barr virus (EBV), plasma level of 1-3-beta-d-Glucan (BDG) was measured using ELISA. High-sensitivity C-reactive protein (hsCRP) was measured using nephelometric method. Results The median age was 36 (IQR 32-44) and 47 (IQR 43–54) years in untreated and virally suppressed patients respectively. Median duration of treatment for virally suppressed patients was 9 years (IQR 7–12) and median baseline CD4 count was 147 cells/mm3 (IQR 65–217). Virally suppressed patients were associated with significantly lower plasma levels of IL-10, sCD14 and BDG (P < 0.05) when compared to untreated patients. However, plasma level of IL-6 was similar between the groups. Baseline advanced level of immunosuppression (CD4 < 100cells/cm3) was associated with significantly higher plasma level of IL-6 (P = 0.02), hsCRP (P = 0.036) and BDG (P = 0.0107). This relationship was not seen in plasma levels of other tested markers. Degree of baseline immunosuppression was not associated with the subsequent proviral DNA copy. In addition, plasma levels of inflammatory marker were not associated with sex, CMV or EBV antibody titers, treatment duration or regimen. Conclusions Our data suggest that advanced immunosuppression at ART initiation is associated with severity of inflammation and elevated fungal translocation marker despite long term virological control. Further studies are needed to evaluate the potential increased burden of non-AIDS comorbidities that are linked to elevated inflammatory and fungal translocation markers as a result of the policy of HIV treatment at CD4 count < 200 cells/cm3 implemented for over a decade in Tanzania.

CMV and HIV Coinfection in Women from a Region in Eastern Europe

“…The study of Gomez-Mora included 228 CMV-seropositive PLWH on ART (with a median of 10 years of therapy) and without a detectable HIV viral load [21]. We considered the threshold of CD4 value as 200 cells/µL (as limit for severe immunosuppression according to published studies [22] and WHO). In our study, in the patients with CD4 ≤ 200 cells/µL, the group average IgG CMV value was smaller than the average value in the CD4 > 200 cells/µL group of patients.…”

A case of central nervous system infection by Candida famata in an immunosuppressed patient with HIV-1 infection

“…More notoriously, the patient had history of severe immunosuppression, with a CD4 + lymphocyte nadir of 16 cells/μL. Severe immunosuppression by advanced HIV has been linked to persistent fungal gut colonization, as well as intestinal barrier disruption, both favoring microbial translocation and infection on long term even after suppressive ART [ 12 ].…”