Background: cART treated PLHIV gaining a large amount of CD4+ T-cells over a short time (''CD4-exploders''; CD4e) or reaching a very high absolute CD4 count (''CD4 peak achievers''; CD4pa) have been recently described. We aimed to characterize these subjects and investigate whether the rate of morbidity/mortality of CD4e or CD4pa may differ from patients who have not present this peculiar CD4 cARTresponses. Methods: We included naïve patients from Icona cohort who have undetectable viral load upon starting cART-. Individuals who gained CD4 >600 cells/mm3 above pre-ART and maintained it for ≥2 consecutive analysis were defined as CD4e; those who achieved a CD4 >1000 cells/mm3 were defined as CD4pa. We estimated the frequency of CD4e and CD4pa by 3 years of suppressive cART and identified factors independently associated with the chance of CD4e/CD4pa using standard survival analysis (Kaplan-Meier curves, Cox model). Participants were further classified according to whether by 3 years of cART they belonged to CD4e or CD4pa and survival analysis was used to compare their risk of sNAE/death. Results: 5,795 subjects were included: by 3 years, the cumulative incidence of CD4e and CD4a was 12% [95% CI (10.8-13.1)] and 10% (8.9-1.9). In multivariable analysis, older age (HR=0.79 per 10 years, 95% CI: 0.71-0.86) and HCV (HR=0.73, 95% CI: 0.54-1.00) were associated with lower chance of CD4e profile. Initiation with PI-based therapy increased the probability of an exploding CD4 response (HR=1.52, 95% CI: 1.28- 1.82). Factors independently associated with greater chance of CD4pa were younger age, without HCV, having started a PI-based regime and a higher CD4 nadir (HR=1.53 per 100 cells/mm3, 95% CI: 1.47-1.59,). Compared to others, subjects with CD4e had a reduced risk of sNAE/deaths (p=0.03) while little difference was observed for CD4pa (p=0.15). Conclusions: By 3 years of effective cART approximately 10% of patients present an extreme CD4 count recovery. Such a CD4 count response is more likely in younger, without HCV and who started a PI-based therapy. People CD4e tended to have a subsequent lower risk of sNAE/death, suggesting that a fast kinetic of immune recovery might be more important than the absolute number achieved.
“CD4 exploders” and “CD4 peak achievers” under ART in a large Italian cohort of HIV-infected subjects / Lichtner, M; Cozzi Lepri, A; Vita, S; Marchetti, G; Sarracino, A; Gori, A; Mussini, C; Madeddu, Giordano; d'Arminio Monforte, A; Icona Foundation Study, Group. - (2015). (Intervento presentato al convegno 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention tenutosi a Vancouver nel 19 - 22 July 2015).
“CD4 exploders” and “CD4 peak achievers” under ART in a large Italian cohort of HIV-infected subjects
MADEDDU, Giordano;
2015-01-01
Abstract
Background: cART treated PLHIV gaining a large amount of CD4+ T-cells over a short time (''CD4-exploders''; CD4e) or reaching a very high absolute CD4 count (''CD4 peak achievers''; CD4pa) have been recently described. We aimed to characterize these subjects and investigate whether the rate of morbidity/mortality of CD4e or CD4pa may differ from patients who have not present this peculiar CD4 cARTresponses. Methods: We included naïve patients from Icona cohort who have undetectable viral load upon starting cART-. Individuals who gained CD4 >600 cells/mm3 above pre-ART and maintained it for ≥2 consecutive analysis were defined as CD4e; those who achieved a CD4 >1000 cells/mm3 were defined as CD4pa. We estimated the frequency of CD4e and CD4pa by 3 years of suppressive cART and identified factors independently associated with the chance of CD4e/CD4pa using standard survival analysis (Kaplan-Meier curves, Cox model). Participants were further classified according to whether by 3 years of cART they belonged to CD4e or CD4pa and survival analysis was used to compare their risk of sNAE/death. Results: 5,795 subjects were included: by 3 years, the cumulative incidence of CD4e and CD4a was 12% [95% CI (10.8-13.1)] and 10% (8.9-1.9). In multivariable analysis, older age (HR=0.79 per 10 years, 95% CI: 0.71-0.86) and HCV (HR=0.73, 95% CI: 0.54-1.00) were associated with lower chance of CD4e profile. Initiation with PI-based therapy increased the probability of an exploding CD4 response (HR=1.52, 95% CI: 1.28- 1.82). Factors independently associated with greater chance of CD4pa were younger age, without HCV, having started a PI-based regime and a higher CD4 nadir (HR=1.53 per 100 cells/mm3, 95% CI: 1.47-1.59,). Compared to others, subjects with CD4e had a reduced risk of sNAE/deaths (p=0.03) while little difference was observed for CD4pa (p=0.15). Conclusions: By 3 years of effective cART approximately 10% of patients present an extreme CD4 count recovery. Such a CD4 count response is more likely in younger, without HCV and who started a PI-based therapy. People CD4e tended to have a subsequent lower risk of sNAE/death, suggesting that a fast kinetic of immune recovery might be more important than the absolute number achieved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
