Background:  Primary HIV-1 infection involves a highly dynamic relationship between virus and host. The development of symptoms of acute retroviral syndrome typically coincides with high-level viremia and the host’s initial immune response. However, clinically severe presentations during acute HIV-1 infection are unusual.

Methods:  A 26-year-old male and a 15-year-old female were admitted to 2 different Spanish hospitals with primary HIV-1 infection. Transmission from donor to recipient was characterized for one of the cases. Viruses were isolated and expanded from peripheral blood mononuclear cells (PBMC) from the first available sample. Viral co-receptor usage was assessed in U87.CD4 cells expressing either CCR5 or CXCR4. The growth rate was determined in stimulated PBMC. Pol (protease and RT) and env (C2-V3) genes were sequenced for subtyping determination and drug susceptibility. Molecular clonal analysis was performed in env sequences. HLA Class I and II genotypes were determined.

Results:  We describe one fatal case of acute respiratory distress syndrome due to P. jiroveci pneumonia and another severe case of disseminated cryptococcal meningitis during primary HIV infection after sexual transmission of highly replicative dual-tropic HIV-1 (subtypes B and CRF02-AG). Presence of HLA B*3503 and common HLA-A and HLA-B supertypes might have contributed to the development of AIDS-defining symptoms.

Conclusions:  Sexual transmission of highly replicative R5/X4 dual/mixed HIV-1 was associated with severe primary infection in 2 unrelated young subjects. Host adaptive cellular and humoral immune responses might have simultaneously failed to control the virus. From a public health perspective, these cases emphasize the continued need for prevention measures.