Abstract:
OBJECTIVE : Untreated perinatal HIV-1 infection is often associated with rapid disease progression in children with HIV (CWH), characterized by high viral loads and early mortality. TRIM22 is a host restriction factor, which directly inhibits HIV-1 transcription, and its genotype variation is associated with disease progression in adults. We tested the hypothesis that TRIM22 genotype is associated with disease progression in CWH.
DESIGN : ART-naive CWH, aged 6–16 years, were recruited from primary care clinics in Harare, Zimbabwe. We performed a candidate gene association study of TRIM22 genotype and haplotypes with markers of disease progression and indicators of advanced disease.
METHODS : TRIM22 exons three and four were sequenced by Sanger sequencing and single nucleotide polymorphisms were associated with markers of disease progression (CD4+ T-cell count and HIV viral load) and clinical indicators of advanced HIV disease (presence of stunting and chronic diarrhoea). Associations were tested using multivariate linear and logistic regression models.
RESULTS : A total of 241 children, median age 11.4 years, 50% female, were included. Stunting was present in 16% of participants. Five SNPs were analyzed including rs7935564, rs2291842, rs78484876, rs1063303 and rs61735273. The median CD4+ count was 342 (IQR: 195–533) cells/μl and median HIV-1 viral load 34 199 (IQR: 8211–90 662) IU/ml. TRIM22 genotype and haplotypes were not associated with CD4+ T-cell count, HIV-1 viral load, stunting or chronic diarrhoea.
CONCLUSION : TRIM22 genotype was not associated with markers of HIV disease progression markers or advanced disease in CWH.
