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.