A complex human immunodeficiency virus type 1 A/G/J recombinant virus isolated from a seronegative patient with AIDS from Benin, West Africa.

A human immunodeficiency virus type 1 (HIV-1(B76)) originating from Benin (West Africa) was isolated and characterized. The patient had severe clinical AIDS and presented an unusual serological profile. Only one out of five different detection assays was able to demonstrate the presence of antibodies to HIV, whereas confirmatory assays remained indeterminate. In contrast, both plasma viral load and p24 antigen level were unusually high. HIV-1 infection was proved by viral RNA and proviral DNA amplification. HIV-1(B76) partially purified lysate reacted strongly with all anti-HIV-1-positive sera from the region but B76 plasma did not react with subtype A control viral antigen. This patient is likely to have had severe acquired immune dysfunction explaining her lack of immunological reactivity. Phylogenetic analysis of the genome identified a complex HIV-1 A/G/J recombinant. The gag and pol genes, and the majority of nef,are characteristic of subtype A; the gag/pol junction, the 3' end of pol, vpu and env genes were characteristic of subtype G; vif, vpr and the 5' end of nef were subtype J. In addition, part of the HIV-1(B76) genome had considerable sequence similarity with the previously described CRF06 cpx (BFP90) isolate. HIV-1(B76) did not exhibit any remarkable replication properties or cell tropism in vitro.

AIDS in an HIV-seronegative Ghanaian woman with intersubtype A/G recombinant HIV-1 infection.

A 29-year-old Ghanaian woman who developed AIDS while being HIV-antibody seronegative was investigated during a collaborative study aimed at the identification of viral causes of a HIV-seronegative AIDS syndrome in West Africa. Plasma was screened with a panel of EIA tests for antibodies to HIV and HIV-1 p24 antigen. Retroviral infection was investigated by detection of reverse transcriptase (RT) activity in plasma, viral RNA amplification and quantification, and virus isolation. Positive amplification products were sequenced and phylogenetic analyses were carried out. Most EIA tests were unable to demonstrate the presence of anti-HIV anti-bodies, whereas confirmatory assays yielded inconclusive results. Retroviral infection was documented by detection of RT activity, HIV-1-specific genomic amplification and virus isolation. This virus was HIV-1 subtype A with an unusual six amino acid insertion in the gp120 V4 loop and with the nef gene of subtype G. The patient's plasma did not react with either autologous or heterologous viral lysates or HIV-1 peptides, whereas antibodies to other viral antigens were present. In conclusion, the Ghanaian patient exhibited a rare subtype A/G recombinant HIV-1 infection with a near absence of a HIV-specific humoral response. The lack of detectable antibody response might be due to either a highly pathogenic, rapidly fatal, HIV-1 infection preventing the development of the typical humoral immune response or to a host-related dysfunction of the immune system. Direct antigenemia or genomic detection of the virus should be undertaken when clinical or biological data suggests an HIV infection in the absence of serological evidence.