Contribution of immunological and virological factors to extremely severe primary HIV type 1 infection.
BACKGROUND
During acute human immunodeficiency virus (HIV) infection, high viral loads and the induction of host immune responses typically coincide with the onset of clinical symptoms. However, clinically severe presentations during acute HIV type 1 (HIV-1) infection, including AIDS-defining symptoms, are unusual.


METHODS
Virus isolates were tested for clade, drug susceptibility, coreceptor use, and growth rate in 2 case reports of sexual transmission of HIV-1 infection. Human leukocyte antigen (HLA) genotype was determined, and HIV-1-specific cytotoxic T lymphocyte responses to an overlapping peptide set spanning the entire HIV clade A and clade B proteome were assayed.


RESULTS
The viruses isolated in the 2 unrelated case reports of severe primary HIV-1 infection showed R5/X4 dual-mixed tropism, belonged to clade B and CRF02-AG, and were highly replicative in peripheral blood mononuclear cell culture. Impaired humoral responses were paralleled by a profound absence of HIV-1-specific cytotoxic T lymphocyte responses to the entire viral proteome in the 2 case reports. In 1 case report for which the virus source was available, there was a remarkable HLA similarity between the 2 patients involved in the transmission event, because 3 of 4 HLA-A and HLA-B alleles had matched HLA supertype for both patients.


CONCLUSIONS
The data suggest that concurrence of viral and host factors contributes to the clinical severity of primary HIV-1 infection and that patients infected with highly replicative, dual-tropic viruses are more prone to develop AIDS-defining symptoms during acute infection if they are unable to mount humoral and cellular HIV-1-specific immune responses. The presence of concordant HLA supertypes might facilitate the preferential transmission of HLA-adapted viral variants, further accelerating disease progression.
Dalmau
Judith
J
irsiCaixa Foundation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Puertas
Maria Carmen
MC
Azuara
Marta
M
Mariño
Ana
A
Frahm
Nicole
N
Mothe
Beatriz
B
Izquierdo-Useros
Nuria
N
Buzón
Maria José
MJ
Paredes
Roger
R
Matas
Lourdes
L
Allen
Todd M
TM
Brander
Christian
C
Rodrigo
Carlos
C
Clotet
Bonaventura
B
Martinez-Picado
Javier
J
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D015728:Receptors, HIV / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015483:HIV Antibodies; D006680:HLA Antigens; D015728:Receptors, HIV