471 Natural Resistance to Viral Replication in HIV-1 Infected Individuals N. Kloosterboer*1, P. Groeneveld2, C.A. Jansen1, K. Brinkman3, C.N. Winkel4, A.J. Duits4, D. van Baarle1, R.P. van Rij1, H. Schuitemaker1 1Sanquin Res at CLB and Academic Med Ctr, Amsterdam, The Netherlands; 2Isala Clinics, Zwolle, The Netherlands; 3Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands; and 4Red Cross Bloodbank Curacao, Willemstad, The Netherlands
Background: During normal HIV infection antibodies against HIV proteins, HIV RNA, and HIV proviral DNA can be found. In this study, we analyzed four HIV-1 infected individuals, who have antibodies against all HIV-1 proteins but who lack any detectable HIV p24 antigen, HIV-1 RNA and HIV-1 proviral DNA. The absence of proviral DNA in untreated HIV-1 infected persons is exceptional and has never been reported before.
Methods: The underlying mechanism for this controlled HIV infection was studied. We determined host genetic factors, the presence of HIV specific cellular and humoral immunity and the in vitro HIV susceptibility.
Results: One (1) individual was heterozygous for a 32 bp deletion in CCR5, a polymorphism previously associated with long-term asymptomatic survival with HIV. Three (3) individuals carry the HLA-B*57 allele and 2 of them additionally have the HLA-B*3501 allele. These alleles are strongly associated with delayed HIV-1 disease progression. The 4th individual was typed for HLA-B*58, which is closely related to HLA-B*57.
HIV-specific cellular immunity could be demonstrated with tetramer staining and ELIspot. The sera of all individuals showed strong antibody mediated neutralization of both CCR5 and CXCR4 utilizing HIV-1 variants. None of the individuals showed evidence for a chronically activated immune system which is in contrast to the generally observation in HIV-infected individuals. The PBMC of all individuals demonstrated a reduced susceptibility for HIV-1 infection compared to the susceptibility of PBMC from a control group that consisted of healthy blood donors.
Conclusions: This is the first identification of individuals with HIV-positive serology but absent viremia. This controlled HIV-1 infection seems to be associated with HLA-B*57/-B*58 HIV specific cellular immunity and strong HIV specific humoral immune responses, as well as reduced HIV-1 susceptibility.
