Description
AIDS Related Genes (ARGs) polymorphisms impacting disease progression in HIV infected children and adolescents perinatally infected in Cameroon
Béatrice Dambaya1,2, Céline Nkenfou1,3, Linda Mekue4, Georges Této1, Nicole Ngoufack2, Njiokou Flobert1, Vittorio Colizzi5 and Alexis Ndjolo1,6.
1Chantal Biya International Reference Centre for research on HIV/AIDS prevention and management (CBIRC), Yaoundé, Cameroon; 2Faculty of Sciences, University of Yaoundé I, Cameroon; 3Higher Teachers' Training College, University of Yaounde I; 4Faculty of Sciences, University of Dschang, Cameroon; 5University of Rome Tor Vergata, Rome Italy; 6Faculty of Medicine and biomedical Sciences, University of Yaoundé I, Cameroon
Background: Pediatric HIV shows heterogeneity in term of vulnerability regarding the infection. Here we investigated some AIDS Related Genes (ARGs) and described their distribution in slow progressors (SP) and long term non progressors (LTNP) and exploited the effects of their various polymorphisms in disease progression.
Methods: We analyzed blood sample of 129 children/adolescents, aged 1 to 15 years old. Among them 52 were HIV perinatally infected and 77 HIV negative among which 31 were HIV exposed uninfected (HEU) and 46 HIV non exposed uninfected (HNEU). HIV positive patients were coming at Chantal Biya International Reference Centre (CBIRC) for biological examinations and 5 were LTNP and 47 SP. Upon signed a proxy consent, their age, CD4, viral load at the set point and clinical symptoms were recorded. Biological analysis was done each six months and the polymorphisms of 5 ARGs, Trim 5α, CCR5, CCR5 promoter, CCR2 and SDF 3'A were investigate. HEU and HNEU were used as control group. p<0.05 was considered statically significant.
Results: There was no significant difference when comparing CD4 (CD4 T cells and percentage) between SP and LTNP in the population, but a significant difference was observed with CD4 T cells when comparing naïve ARV patients (p=0.04) and LTNP. A significant difference between the two groups was observed for viral load (p=0.03) in the overall population, a high difference was seen when comparing only SP naïve with LTNP with both viral load copies and log (p=0.01; p=0.005). The genotype analysis did not show any significant deviation from the Hardy-Weinberg expected frequency. Among the 5 genes, the protective allele of Trim5α (R136Q) was present in all LTNP and in 72.34% of SP. The CCR5 promoter 59029G was present in 60% of LTNP and in 34,04% of SP. CCR2V64I was almost absent, only the heterozygous form of the allele was represented with a significant difference between SP vs LTNP (p=0.0002). R136Q allele was more present in HEU than in HNEU (p<0.0001), a significant difference was observed between HNEU and SP, LTNP (p<0.0001; p=0.01). A significant difference between the two groups was in contrary observed with HEU (p<0.0001; p=0.01), with CCR5 promoter 59029G. CCR5∆32 was completely absent, SDF 3'A was almost absent in heterozygous form and completely absent in homozygous form.
Conclusion: Among the 5 genes described in the study, 3 of them, Trim 5α, CCR5 promoter and CCR2V64I retained need to be more investigated. The role of CCR5 promoter 59029G appears to be controversial.
Keys words: AIDS, Genes, Children/Adolescents, Perinatally infected, Progressors