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
