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Open Access Research

Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency

Torsak Bunupuradah1*, Mayumi Imahashi23, Thatri Iampornsin1, Kazuhiro Matsuoka2, Yasumasa Iwatani23, Thanyawee Puthanakit14, Jintanat Ananworanich156, Jiratchaya Sophonphan1, Apicha Mahanontharit1, Tomoki Naoe3, Saphonn Vonthanak7, Praphan Phanuphak1, Wataru Sugiura23 and on behalf of the PREDICT Study Team

Author Affiliations

1 HIV-NAT, the Thai Red Cross AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok, 10330, Thailand

2 Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

3 Program in Integrated Molecular Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan

4 Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

5 Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

6 SEARCH, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand

7 Social Health Clinic, Phnom Penh, Cambodia

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AIDS Research and Therapy 2012, 9:34  doi:10.1186/1742-6405-9-34

Published: 24 November 2012

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.

Keywords:
APOBEC3G; Treatment-naïve; HIV-infected children; Disease progression; PREDICT