Non-myristoylated Nef HIV-1 variant may account for persistent in vivo discordance of CD4+ count and viral load in a vertically infected child

CORRÓ, GUILLERMO; DE MAIO, FEDERICO ANDRÉS; ROCCO, CARLOS; AULICINO, PAULA; SVARTZ, ALEJANDRA; MANGANO, ANDREA; SEN, LUISA

Ciudad de México

Conferencia; XVII International AIDS Conference; 2008

International AIDS Society (IAS)

Usually in HIV-1 infected individuals viral load and CD4+ T cell count inversely correlate. However, patients under HAART showing persistently normal CD4+ cell counts but high viral loads are becoming more frequent. To investigate if HIV-1 may be responsible of the discordance, different accessory and structural viral genes were amplified and sequenced from a perinatally infected child with CD4+ cell/virus load discordance. Peripheral blood mononuclear cells and plasma mainly obtained after 8 years old were studied. He is a 15 year old boy that has been under HAART for 11 years and since the age of 5 always had viral loads higher than 10,000 RNA copies/ml and CD4+ higher than 500 cells/ìl. At 3 different time points, differing 55 months between each point, the accessory nef gene showed the presence of a 27bp deletion at 3?end predicting the lack of the myristoylation site at amino terminal of the protein as a persistent defect. The other 2 accessory genes vif and vpr did not reveal any significant alteration. In terms of the structural genes studied, multiple resistance mutations to all the ARV drugs received were observed on pol, while in env-V3 no significant modifications were observed. At 14 years old the HIV-1 isolate presented a syncytium inducing phenotype, but the env-V3 did not show the expected positive charged residues at positions 11/25. This is the first case reported of a vertically infected infant carrying a persistent non-myristoylated Nef HIV-1 variant with high replication rate, highly resistant to all the ARV received, with a predicted aggressive phenotype for immune system but apparently unable to injure CD4+ T cells.