IL7RA rs6897932 Polymorphism is Associated with Better CD4+ T-Cell Recovery in HIV Infected Patients Starting Combination Antiretroviral Therapy

Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4+ recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4+ T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4+ T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4+ T-cells count 20% and was in Hardy-Weinberg equilibrium (p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4+ T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4+ T-cells increase (AMR = 1.19; p = 0.004), and higher CD4+ T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4+ T-cells at the end of follow-up ≥500 CD4+ cells/mm3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of ≥ 400 CD4+ cells/mm3 lost statistical significance (p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4+ T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4+ T-cells count <200 cells/mm3.This study has been (partially) funded by grants RD12/0017/0031 and RD16/0025/0013 to JMB, and RD12/0017/0024 and RD16CIII/0002/0002 to SR as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008–2011; 2013–2016) and co-financed by Institute of Health Carlos III, ISCIII—Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). MA Jiménez-Sousa is funded by project RD16CIII/0002/0002; MA Navarrete-Muñoz is co-funded by RD16/0025/0013 project and Intramural Research Scholarship from IIS-FJD. N Rallón is a Miguel Servet investigator from the ISCIII [grant number CP14/00198].S

Mitochondrial haplogroup H is related to CD4+ T cell recovery in HIV infected patients starting combination antiretroviral therapy

BACKGROUND: The mitochondrial DNA (mtDNA) seems to influence in a large number of diseases, including HIV infection. Moreover, there is a substantial inter-individual variability in the CD4+ recovery in HIV-infected patients on combination antiretroviral therapy (cART). Our study aimed to analyze the association between mtDNA haplogroups and CD4+ recovery in HIV-infected patients on cART. METHODS: This is a retrospective study of 324 naïve cART patients with CD4+  9.65 CD4+ cells/mm3/month) than patients without haplogroup H (p = 0.032). The adjusted logistic regression showed that patients carrying haplogroup H had a higher likelihood of achieving a CD4+ recovery > 9.65 CD4+ cells/mm3/month [adjusted odds ratio (aOR) = 1.75 (95% CI = 1.04; 2.95); p = 0.035]. CONCLUSIONS: European mitochondrial haplogroup H was associated with the improved CD4+ recovery in HIV-infected patients starting cART with CD4+ < 200 cells/mm3.This work has been (partially) funded by Grants RD12/0017/0024 and RD16CIII/0002/0002 to SR, and RD12/0017/0031 and RD16/0025/0013 to JMB as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008–2011; 2013–2016) and co-financed by Institute of Health Carlos III, ISCIII–Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). Luz Mª Medrano is supported by Spanish Carlos III Institute of Health (ISCIII) Madrid, Spain [Grant Number CD14/00002]. N Rallón is a Miguel Servet investigator from the ISCIII [Grant Number CP14/00198]; M. García is a predoctoral student co-funded by CP14/00198 Grant and Intramural Research Scholarship from IIS-FJD. The authors would like to thank the Spanish National Genotyping Center (CEGEN-PRB2-ISCIII) for providing SNP genotyping services (http://www.cegen.org). CEGEN is supported by grant PT13/0001, ISCIII-SGEFI/FEDER. We also acknowledge the patients in this study for their participation and the Centro de Transfusión of Comunidad de Madrid for the healthy donor blood samples provided. We acknowledge the Spanish HIV-1 BioBank integrated into the Spanish AIDS Research Network (RIS) and collaborating centers for the clinical samples provided. The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by ISCIII, Spanish Health Ministry (Grant nº RD06/0006/0035 and RD12/0017/0037) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII–Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF) and Foundation for Research and Prevention of AIDS in Spain (FIPSE). The RIS Cohort (CoRIS) is funded by the ISCIII through the Spanish AIDS Research Network (RISC03/173 and RD12/0017/0018) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII–Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF).S

Genetic variation in CCR2 and CXCL12 genes impacts on CD4 restoration in patients initiating cART with advanced immunesupression.

OBJECTIVE:We 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. METHODS:A 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. RESULTS:Thirty 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). CONCLUSIONS:CCR2 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