Abstract
BackgroundFor 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.
Highlights
Antiretroviral therapy (ART) is responsible for the reduction in AIDS related deaths and improvement of life expectancy among people living with HIV (PLHIV)
We found no significant relationship between plasma BDG and markers of inflammation (IL6, IL-10 and High-sensitivity C-reactive protein (hsCRP)) or monocyte activation (Table 2)
We observed a similar trend in the level of hsCRP where, virally suppressed patients in the lowest quantile of baseline CD4 count had higher levels compared to those in the highest quantile (P = 0.036) (Fig. 3g). This relationship was not seen in plasma levels of soluble CD14 (sCD14) or IL-10 in both groups (Fig. 3e and f )
Summary
Antiretroviral therapy (ART) is responsible for the reduction in AIDS related deaths and improvement of life expectancy among people living with HIV (PLHIV). Morbidity and mortality from conditions like metabolic syndrome, non AIDS defining cancers, cardiovascular diseases and neurocognitive disorders are disproportionally common among PLHIV [1,2,3,4]. These conditions (collectively referred as non-AIDS comorbidities) are closely linked to inflammation and immune activation. 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
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