Abstract
Objectives: Chemokines influence the migration of leukocytes to secondary lymphoid tissue and sites of inflammation. In HIV patients, they are implicated in inflammatory complications of antiretroviral therapy (ART), notably Immune Reconstitution Disease (IRD) and Sensory Neuropathy (SN). However most chemokines have not been monitored as patients begin ART or correlated with IRD and SN.Methods: Plasma chemokine levels were assessed longitudinally using commercial ELISAs in 69 patients treated in Kuala Lumpur, Malaysia. Plasma was available at baseline and after 6, 12, 24 and 48 weeks on ART. Chemokine genotypes were assessed using allele-specific fluorescent probes. IRD were diagnosed in 15 patients. 30 patients were screened for SN using the ACTG BPNS tool after six months on ART. SN was detected in 8 patients.Results: Plasma CXCL10 levels decreased on ART compared to baseline (p= 0.002–0.0001), but remain higher than healthy controls (p≤ 0.0001). The decline was clearer in patients without IRD. CCL5 levels rose on ART but remained similar to controls. CCL2 levels were higher in patients than controls after week 12. Plasma chemokine levels were not affected by CD4+ T-cell counts or any genotypes tested. Several patients with SN displayed higher CCL5 levels throughout therapy compared to patients without neuropathy. Levels of other chemokines and chemokine genotypes were not associated with SN.Conclusions: Chemokines are differentially affected by ART. CXCL10 and CCL5 may influence IRD and CCL5 warrants further investigation for an effect in SN. These trends are not influenced by chemokine genotypes investigated here.
Highlights
Antiretroviral therapy (ART) has improved life expectancy in HIV-infected individuals by suppressing viral replication and reducing opportunistic infections.several adverse effects compromise both patient health and adherence to therapy
CXCL10 levels were lower after 6 weeks on ART compared to baseline (p = 0.002– < 0.0001; Wilcoxon rank-sum), but remained higher than healthy controls (p 0.0001; Mann Whitney)
The association between decreasing log CXCL10 levels and time on ART was confirmed using a linear regression model clustered by patient (p 0.0001, r2 = 0.18) (Fig. 1a)
Summary
Antiretroviral therapy (ART) has improved life expectancy in HIV-infected individuals by suppressing viral replication and reducing opportunistic infections. Several adverse effects compromise both patient health and adherence to therapy. These include Sensory Neuropathy (SN) [1] and Immune Reconstitution Disease (IRD) [2,3]. Both are characterized by dysregulated host inflammatory responses [4,5]. Circulating chemokines may be a component of functional immune reconstitution or may mediate SN or IRD. Chemokines are critical for inflammation and the induction of adaptive immune responses, but the effects of ART on chemokines are not well characterized, and
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