AEGiS-15IAC: Differences in disease progression in a cohort of long-term non-progressors with more than 16 years of HIV infection.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Differences in disease progression in a cohort of long-term non-progressors with more than 16 years of HIV infection.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10440)

Rodes B, Toro C, Poveda E, Martinez-Padial M, Jimenez V, Soriano V
Hospital Carlos III, Madrid, Spain

BACKGROUND: It is unclear whether absence of immunologic damage in long-term non-progressors (LTNP) will last indefinitely or merely represents the end of a gaussian distribution, and therefore progression will eventually occur.

METHODS: A cohort of 25 LTNP was established in our hospital (LTNP are 1% of all outclinic patients). All had HIV-1 infection for at least 10 years without treatment, CD4 above 500 cells/mm³ and lacked HIV-related symptoms. Plasma HIV-RNA (pVL) and CD4 count were measured 2-3 times/year. Characterization of nef and vpr viral genes, CCR5 genotypes, co-receptor tropism, viral replication capacity and T-cell activation was performed.

RESULTS: 14 out of 25 patients were male and 21 were former IDUs. 19 subjects had stable CD4 over time and were classified as non-progressors (NP); while 6 subjects (slow progressors, SP) showed a trend towards progressive CD4 depletion (average loss of 40 cell/mm³/year). All SP had detectable pVL (median 3437 cop/ml) at more than one time. In contrast, 6 of the 19 subjects with stable CD4 had always undetectable pVL (median in NP: 718 cop/ml). All viruses belonged to subtype B. None but one had deletions in nef. Analysis of Vpr showed that 7 out of 18 analyzed patients had the R77Q change. There were no differences in the presence of 77Q between both groups. All patients carried R5 viruses. One subject showed a shift from R5 to a mixed X4/R5 virus population which was coincident with a loss of 80 cells/mm³/year. Virus replicative capacities were tested in 8 individuals, in all of whom was reduced compared to wild type (range 5-93%). No patient was homozygous for Gamma-32 CCR5, found in heterozygosis in 4 subjects. Finally, the mean CD8 activation was low with no differences between NP or SP.

CONCLUSIONS: A substantial number of LTNP shows a progressive loss of CD4 cells over time. All of them have detectable viremia and many carry viruses with low replicative capacity and CCR5 tropism. Progressive immunologic damage seems directly associated with some degree of virus replication.

Keywords: AEGIS, Disease Progression, HIV Infections, Receptors, CCR5, CD4 Lymphocyte Count, Acquired Immunodeficiency Syndrome, Genes, vpr, CD4-Positive T-Lymphocytes, Viremia, Virus Replication, HIV Seropositivity, Lymphocyte Activation, Male, Humans, genetics, virology, immunology, epidemiology

040711
A10440