Incidence and Predictors of All-cause Death, Liver-related Death, and AIDS in an Incident Cohort of HIV+ Patients with Cirrhosis Estimated by FIB-4 Score
S Digiambenedetto1, M Prosperi1, Emanuele Focą*2, M Colafigli1, F Maggiolo3, N Ladisa4, G Lapadula5, A Pan6, N Marino7, C Torti2, and MASTER Cohort Study Group
1Catholic Univ of the Sacred Heart, Rome, Italy; 2Univ of Brescia, Italy; 3Ospedali Riuniti, Bergamo, Italy; 4Policlinico di Bari, Italy; 5San Gerardo Hosp, Monza, Italy; 6Istituti Ospedalieri, Cremona, Italy; and 7SM Annunziata Hosp, Florence, Italy
Background: HIV+ patients with cirrhosis remain at a significant risk of complications, however there is a paucity of data to assess their risk and the predictors of death (either for any causes or for liver diseases) or AIDS.
Methods: We selected for this observational prospective study HIV patients with detectable hepatitis C virus (HCV) RNA, not exposed to interferon/ribavirin, in a large Italian cohort from the time when their FIB-4 score (Sterlings formula) evolved to >3.25 (confirmed). The date of the first FIB-4 >3.25 was the baseline. Kaplan-Meier analysis was used to estimate the incidence of AIDS, liver-related death (LRD), and all-cause death (ACD). Cox regression analysis was used to assess the predictors (either baseline or time-dependent) of the 3 outcomes.
Results: We observed 731 patients for a mean of 1590 days. The incidence of AIDS was 0.049 per person-year of follow-up, whereas the incidence of LRD and ACD were: 0.023 and 0.050 per person-year of follow-up, respectively. In multivariable analysis, higher CD4+ count (per Log higher) throughout the follow-up predicted a lower risk of AIDS (HR 0.28, 95%CI 0.20 to 0.37, p <0.0001), LRD (HR 0.28, 95%CI 0.19 to 0.43, p <0.0001), and ACD (HR 0.27, 95%CI 0.20 to 0.37, p <0.0001). In the same model, stopping cART vs continuing any regimens including protease inhibitors (PI) predicted a greater risk of LRD (HR 3.37, 95%CI 2.02 to 5.64, p <0.0001) and ACD (HR 1.98, 95%CI 1.34 to 2.92, p = 0.0006). Age (per year older) predicted the risk of AIDS (HR 1.08, 95%CI 1.04 to 1.11, p <0.0001) and ACD (HR 1.04, 95%CI 1.01 to 1.07, p = 0.0038), but not the risk of LRD. HIV RNA control was significantly associated with a reduction in the risk of AIDS (HR 0.30, p <0.001 for <500 copies/mL vs 500 to 10.000 copies/mL and >10.000 copies/mL), but this was not confirmed for the death outcomes. Unknown HCV genotype (vs genotype 1) appeared to increase both the risk of LRD (HR 2.41, p = 0.0048) and ACD (HR 2.65, p <0.0001).
Conclusions: Survival of patients with advanced liver fibrosis depended strongly on the degree of immune recovery and on continuing cART including a PI, which appeared to counteract both LRD and ACD. Sustained HIV RNA control and younger age appeared to decrease the risk of AIDS but these factors did not emerge as significant predictors of LRD in this cohort of HIV/HCV-co-infected patients. Lastly, we hypothesize that the impact of undetermined HCV genotype is a surrogate for a suboptimal standard of care, thereby influencing the risk of death.