Int Conf AIDS 1994 Aug 7-12; 10:50 (abstract no. PS10) Ho DD; Aaron Diamond AIDS Research Center, New York, New York 10016.
We have studied 10 long-term non-progressors who are healthy with normal CD4 counts despite HIV-1 infection for 12-16 years. Extremely low levels of virus were detected in their plasma and PBMC. Routine HIV cultures were distinctive in that they were negative in 8 of 10 patients. When a standard strain of HIV-1 was added exogenously to the PBMC of each subject, viral replication was absent or blunted. This was not attributable to an inherent resistance of CD4 cells, but due instead to a potent CD8+, virus-inhibitory response. We have also found that the sera from these patients exhibited strong and broad neutralizing activity against a panel of primary HIV-1 isolates. In addition, in characterizing the available HIV-1 isolates, it was evident that 2 viruses grew so poorly in vitro that they appeared defective. However, all 10 non-progressors had intact nef genes, and DNA sequencing and functional studies have not revealed any apparent defect in nef. Our preliminary conclusions are: 1) Long-term non-progressors have distinctive virologic and immunologic features to suggest that they are not merely "one extreme on a normal distribution curve." 2) Their HIV-1 is well controlled, perhaps in part due to the strong CD8+, virus-inhibitory cellular response as well as potent neutralizing antibodies; the persistence of these responses implies continued exposure of the immune system to viral antigens in vivo. 3) The low level of viremia may also be due to infection by attenuated strains of HIV-1; however, in our cases, we have no evidence for nef defects to account for the viral attenuation.
Keywords: AEGIS, HIV-1, HIV Infections, Genes, nef, CD4 Lymphocyte Count, HIV Long-Term Survivors, HIV Antibodies, HIV, Virus Replication, HIV Long Terminal Repeat, Antigens, CD4, Antigens, CD8, In Vitro, Human, genetics, virology, ICA10 940807
PS10
