Background:  HLA is considered a genetic co-factor for AIDS progression. HLA alleles have been associated both with rapid and slow progression to AIDS. It is likely that the ability to present efficiently HIV-1 epitopes is crucial for the development of an efficient immune response.

Methods:  A group of 248 HIV⁺ children from a cohort of 418 subjects infected during an outbreak in the Benghazi Children Hospital in Lybia, Bulgaria, in 1998, has been evaluated for viral and host parameters in the context of clinical outcomes. High-resolution HLA typing was performed in 109 children. HIV-1 sequences of gag, tat, vpr, and vpu genes where performed on 47 subjects of the cohort and hepatitis C virus (HCV) characterized in 60 co-infected children. HLA-binding motif scans were used to assess the number of gag epitopes that each subject is capable of presenting in the context of the subject’s own HLA alleles.

Results:  In all 47 cases evaluated, a circulating recombinant clade A/G strain of HIV 1 was found. Phylogenetic analysis showed a high degree of similarity among independent samples and low mutation rate in sequential samples analyzed in different years. HCV was present in 75of 174 (43.1%) HIV⁺ children studied. HCV sequences from 60 of them clustered into 3 main groups. Neither the HCV co-infection nor the co-infection of a particular HCV strain was associated with disease progression. HLA typing showed a significant difference in allele distribution between children progressing or not progressing to AIDS only in the HLA-B locus. An increase of the HLA-B58 supertype alleles was observed in the non-progressing children (16 of 51, 31.4% vs 3 of 58, 5.1%; p = 0.008) while HLA-B8 type resulted increased in children progressing to AIDS (11 of 58, 19.0% vs 1 of 51, 2.0%; p = 0.001). The analysis of the number of putative epitopes that each subject could present in the subject’s own HLA-B alleles along the gag protein sequence circulating in the cohort showed that subjects with disease progression had a lower capability to present gag epitopes (73.6±3.7 [mean±SEM]) with respect to not progressing to AIDS (87.5±5.1; p = 0.031).

Conclusions:  The analysis of disease progression host factors of children infected with a monophyletic circulating recombinant clade A/G strain of HIV-1 coming from a defined geographic area suggest that behind the HLA association with progression or non-progression to AIDS there could be a reduced capability to present HIV-1 CD8-restricted T-cell epitopes in subjects who progress faster to AIDS.