Abstract
ObjectiveWe investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts.MethodsA case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count <200 cells/μL and successful viral control for two years. CD4 count increase below 200 cells/μL after two years on cART was used to define INR (immunological non-responder) patients. Polymorphisms in CXCL12, CCL5 and CCR2 genes were genotyped using sequenom’s MassARRAY platform.ResultsThirty two percent (134/412) of patients were classified as INR. After adjusting by age, route of HIV infection, length of infection before cART and viral hepatitis coinfection, CCR2 rs1799864-AG genotype was significantly associated with INR status (OR [95% CI]: 1.80 [1.04–3.11]; p = 0.04), and CXCL12 rs1801157-TT genotype showed a trend (OR [95% CI]: 2.47 [0.96–6.35]; p = 0.06).ConclusionsCCR2 rs1799864-AG or CXCL12 rs1801157-TT genotypes influence on the probability of poor CD4 recovery in the population of HIV patients starting cART with low CD4 counts. Genotyping of these polymorphisms could be used to estimate the risk of poor CD4 restoration, mainly in patients who are diagnosed late in the course of infection.
Highlights
The progressive loss of CD4 T cells is the hallmark of HIV pathogenesis
Thirty two percent (134/412) of patients were classified as immunological nonresponders (INR)
Despite suppression of viral replication, approximately 30% of HIV-infected patients do not achieve an optimal CD4 T-cell recovery [1,2] and these individuals are referred to as immunological nonresponders (INR) [3]. This phenomenon is of clinical relevance because the persistently low CD4 T cell counts are associated with a high risk of disease progression, AIDS and non-AIDS clinical events and death [4]
Summary
Treatment of HIV infection with combination antiretroviral therapy (cART) usually results in suppression of viral replication to undetectable levels and increasing CD4 T cell counts. Despite suppression of viral replication, approximately 30% of HIV-infected patients do not achieve an optimal CD4 T-cell recovery [1,2] and these individuals are referred to as immunological nonresponders (INR) [3]. This phenomenon is of clinical relevance because the persistently low CD4 T cell counts are associated with a high risk of disease progression, AIDS and non-AIDS clinical events and death [4]. Nadir CD4 T cell count (defined as the lowest point to which the CD4 count has dropped) at the beginning of cART is the most common determinant of poor immune recovery [5,6] representing an important concern because of the high proportion of patients showing CD4 Tcell counts below 350 cells/mm or even
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