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140 Predictors of Disease Progression in LTNP: A 5-Year Follow-Up Study
E. Vicenzi1, S. Ghezzi1, G. Vallanti1, F. Neri1, D. Douek2, E. Santagostino3, A. Gringeri3, M. Cusini3, A. Lazzarin1, F. Veglia4, and G. Poli*1
1San Raffaele Scientific Inst., Milano, Italy; 2Vaccine Res. Ctr., NIH, Bethesda, MD, USA; and 3IRCCS Maggiore Hosp., Milano, Italy
Background: The determinants of disease progression in LTNP are unclear at present.
Methods: A cohort of 47 HIV+ LTNP were monitored between 1994 and 1999 in terms of virological, immunologic, and clinical parameters.
Results: After 5 years, 24/47 individuals, defined here as late progressors (LP), have experienced either loss of CD4+ T cells below 500 and/or have initiated antiviral treatments, although none of them has developed symptoms of clinical progression of HIV disease. By univariate analysis, both low CD4+ T-cell counts and viremia were significantly associated with evolution from LTNP to LP (p = 0.0008 and 0.0011, respectively). Lack of HIV isolation at entry was significantly correlated to maintenance of the LTNP condition (p = 0.0007). In addition, LP showed a superior frequency of SI viruses (p = 0.22 by Fisher’s exact test) than LTNP; isolation of SI viruses was significantly associated with LP (p = 0.0001). When a multivariate analysis with stepwise selections of the variables was performed on the above parameters, only CD4+ T-cell counts at entry and viral phenotype were identified as independent predictors of loss of the LTNP condition (p = 0.010 and 0.024, respectively). As expected, our cohort showed a skewed prevalence of the CCR5-?32 genotype (q = 0.127) in comparison to a general population of uninfected individuals (q = 0.047). Of interest, a significant (p = 0.018) decrease of PBMC-associated TREC occurred during the 5 years of observation among individuals who remained LTNP although no significant variations of CD4+ T-cell number, viremia, and PBMC-associated HIV DNA were seen.
Conclusions: In addition to viremia and CD4+ T-cell counts, viral phenotype and positive HIV isolation are predictors of evolution from the LTNP condition. The observation of a decrease in TREC amongst LTNP suggests that loss of T-cell renewal may represent an early marker of disease progression in these individuals.
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