Published in:
Open Access
01-12-2012 | Research
Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency
Authors:
Torsak Bunupuradah, Mayumi Imahashi, Thatri Iampornsin, Kazuhiro Matsuoka, Yasumasa Iwatani, Thanyawee Puthanakit, Jintanat Ananworanich, Jiratchaya Sophonphan, Apicha Mahanontharit, Tomoki Naoe, Saphonn Vonthanak, Praphan Phanuphak, Wataru Sugiura, the PREDICT Study Team
Published in:
AIDS Research and Therapy
|
Issue 1/2012
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Abstract
Introduction
Human APOBEC3G is a host defense factor that potently inhibits HIV replication. We hypothesize that HIV-infected children with a genetic variant of APOBEC3G will have a more rapid disease progression.
Methods
Antiretroviral therapy (ART)-naïve children, aged 1–12 years old with CD4 15-24% and without severe HIV-related symptoms were enrolled. The children had CD4% and absolute CD4 counts every 12 weeks and HIV-RNA every 24 weeks until 144 weeks. ART was started when CD4% declined to < 15% or AIDS-related events developed.
APOBEC3G genetic variants were performed by PCR-based restriction fragment length polymorphism techniques from peripheral blood mononuclear cells. Random-effect linear regression analysis was performed to correlate APOBEC3G genotypes and disease progression.
Results
147 children, 35% male, with a median (IQR) age of 6.5 (4.3-8.8) years were enrolled. CDC N:A:B were 1:63:36%. Median baseline values were 20% for CD4% 605 cells/mm3 for CD4 count and 4.7 log10copies/mL for HIV-RNA.
The frequencies of APOBEC3G genotypes AA (186H/H), AG (186H/R), GG (186R/R) were 86%, 12%, and 2% respectively. The APOBEC3G genotype GG was associated with a significant decline in CD4% -5.1% (−8.9 to −1.2%), p<0.001, and CD4 counts −226 (−415 to −34) cells/mm3, p<0.001 by random-effect liner regression analysis. No significant associations of APOBEC3G genotypes with HIV-RNA changes overtime (p=0.16) or progression to CDC B and C (p=0.49) were observed.
Conclusions
APOBEC3G genotype GG was significantly associated with a more rapid decline in CD4. APOBEC3G’s antiviral effects on HIV disease progression in children should be further explored.