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

• Main Authors: Luz M. Medrano, Mónica Gutiérrez-Rivas, Julià Blanco, Marcial García, María A. Jiménez-Sousa, Yolanda M. Pacheco, Marta Montero, José Antonio Iribarren, Enrique Bernal, Onofre Juan Martínez, José M. Benito, Norma Rallón, Salvador Resino, CoRIS and the HIV Biobank integrated in the Spanish AIDS Research Network Project RIS/EPICLIN 10_2015
• Format: Article
• Language: English
• Published: BMC 2018-12-01
• Series: Journal of Translational Medicine
• Subjects: HIV; Mitochondria; Haplogroups; mtDNA; Immune reconstitution; cART
• Online Access: http://link.springer.com/article/10.1186/s12967-018-1717-y
• ISSN: 1479-5876

Abstract 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+ < 200 cells/mm3, who were followed-up during 24 months after initiating cART. All patients had undetectable HIV viral load during the follow-up. Besides, we included 141 healthy controls. MtDNA genotyping was performed by using Sequenom’s MassARRAY platform. The primary outcome variable was the slope of CD4+ recovery. Patients were stratified into two groups by the median slope value of CD4+ (9.65 CD4+ cells/mm3/month). Logistic regression analyses were performed to calculate the odds of CD4+ recovery according to mtDNA haplogroups. Results Our study included European HIV-infected patients within the N macro-cluster. The baseline values of CD4+ T-cells were similar between groups of patients stratified by the P50th of the slope of CD4+ T-cells recovery. Patients in the low CD4+ T-cells recovery group were older (p = 0.001), but this variable was included in the multivariate models. When we analyzed the frequencies of mtDNA haplogroups, no significant differences between HIV-infected individuals and healthy controls were found. We did not find any significant association between mtDNA haplogroups and the slope of CD4+ T-cells recovery by linear regression analysis. However, Patients carrying haplogroup H had a higher odds of having a better CD4+ recovery (> 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.