We aimed to characterize non-AIDS events (NAEs) occurring in newly diagnosed HIV-infected patients in a contemporary cohort.
The Cohort of the AIDS Research Network (CoRIS) is a prospective, ...multicenter cohort of HIV-infected adults antiretroviral naive at entry, established in 2004. We evaluated the incidence of and the mortality due to NAEs and AIDS events through October 2010. Poisson regression was used to investigate factors associated with a higher incidence of NAEs.
Overall, 5185 patients (13.306 person-years of follow-up), median age (interquartile range) 36 (29-43) years, participated in the study. A total of 86.5% patients had been diagnosed in 2004 or later. The incidence rate of NAEs was 28.93 per 1000 person-years 95% confidence interval (CI) 26.15-32.07, and of AIDS-defining events 25.23 per 1000 person-years (95% CI 22.60-28.16). The most common NAEs were psychiatric, hepatic, malignant, renal, and cardiovascular related. After adjustment, age, higher HIV-viral load, and lower CD4 cell count at cohort entry were associated with the occurrence of NAEs, whereas likelihood significantly decreased with sexual transmission and higher educational level. Additionally, antiretroviral therapy was inversely associated with the development of some NAEs, specifically of psychiatric incidence rate ratio (95% CI) 0.54 (0.30-0.96) and renal-related incidence rate ratio (95% CI) 0.31 (0.13-0.72) events. One hundred and seventy-three (3.33%) patients died during the study period. NAEs contributed to 28.9% of all deaths, with an incidence rate (95% CI) of 3.75 (2.84-4.94) per 1000 person-years.
In patients newly diagnosed with HIV infection, NAEs are a significant cause of morbidity and mortality. Our results suggest a protective effect of antiretroviral therapy in the occurrence of NAEs, in particular of psychiatric and renal-related events.
Background. We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. Methods. We studied patients ...from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liverrelated events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis—LB (F3 or greater) or FIB-4 (≥3.25)—and outcomes using multivariate Cox regression analysis. Results. The study sample comprised 903 patients (328 with sustained virologic response SVR). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval CI, 1.119–2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463–6.160; P < .001) assessed by FIB-4. Conclusions. FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.
HIV-infected individuals with a history of transmission through injection drug use (IDU) have poorer survival than other risk groups. The extent to which higher rates of hepatitis C (HCV) infection ...in IDU explain survival differences is unclear.
Adults who started antiretroviral therapy between 2000 and 2009 in 16 European and North American cohorts with >70% complete data on HCV status were followed for 3 years. We estimated unadjusted and adjusted (for age, sex, baseline CD4 count and HIV-1 RNA, AIDS diagnosis before antiretroviral therapy, and stratified by cohort) mortality hazard ratios for IDU (versus non-IDU) and for HCV-infected (versus HCV uninfected).
Of 32,703 patients, 3374 (10%) were IDU; 4630 (14%) were HCV+; 1116 (3.4%) died. Mortality was higher in IDU compared with non-IDU adjusted HR 2.71; 95% confidence interval (CI): 2.32 to 3.16 and in HCV+ compared with HCV- (adjusted HR 2.65; 95% CI: 2.31 to 3.04). The effect of IDU was substantially attenuated (adjusted HR 1.57; 95% CI: 1.27 to 1.94) after adjustment for HCV, while attenuation of the effect of HCV was less substantial (adjusted HR 2.04; 95% CI: 1.68 to 2.47) after adjustment for IDU. Both IDU and HCV were strongly associated with liver-related mortality (adjusted HR 10.89; 95% CI: 6.47 to 18.3 for IDU and adjusted HR 14.0; 95% CI: 8.05 to 24.5 for HCV) with greater attenuation of the effect of IDU (adjusted HR 2.43; 95% CI: 1.24 to 4.78) than for HCV (adjusted HR 7.97; 95% CI: 3.83 to 16.6). Rates of CNS, respiratory and violent deaths remained elevated in IDU after adjustment for HCV.
A substantial proportion of the excess mortality in HIV-infected IDU is explained by HCV coinfection. These findings underscore the potential impact on mortality of new treatments for HCV in HIV-infected people.
The aim of this study was to analyse factors associated with progression to AIDS/death in severely immunosuppressed HIV-infected patients receiving ART.
This study included naive patients from the ...PISCIS Cohort with CD4 <200 cells/mm(3) at enrolment and who initiated ART consisting of two nucleoside analogues plus either a PI or an NNRTI between 1998 and 2011. The PISCIS Cohort is a multicentre, observational study of HIV-infected individuals aged >18 years followed at 14 participating hospitals in Catalonia and the Balearic Islands (Spain). Clinical and laboratory parameters were assessed every 3-4 months during follow-up. Cox regression models were used to assess the effect of CD4 and viral load on the risk of progression to AIDS/death, adjusting for baseline variables and confounders.
2295 patients were included and, after 5 years, 69.9% reached CD4 ≥200 cells/mm(3), 64.4% had an undetectable viral load and 482 (21%) progressed to AIDS/death. The lowest rate of disease progression was found in patients who reached both immunological and viral responses during follow-up, regardless of their baseline situation (1.9% in baseline CD4 >100 cells/mm(3) and viral load <5 log copies/mL; 2.3% in baseline CD4 ≤100 cells/mm(3) and/or viral load >5 log copies/mL). Achieving a CD4 count ≥200 cells/mm(3) was the main predictor of decreased progression to AIDS/death. In those not reaching this CD4 threshold, virological response reduced disease progression by half.
Even in the worse baseline scenario of CD4 ≤100 cells/mm(3) and high baseline viral loads, positive virological and immunological responses were associated with dramatic decreases in progression.
Triple combination therapy with pegylated interferon, ribavirin and telaprevir is currently considered the gold standard for the treatment of chronic hepatitis C virus (HCV) infection. The most ...important features are an increase in rates of sustained viral response (74-79% vs 46% with pegylated interferon and ribavirin), as well as the possibility of early cessation of ineffective therapy due to the application of futility rules at weeks 4 and 12 (HCV-RNA > 1,000 UI/ml), and the possibility of selecting candidates for the shortest treatments due to the clinical significance of extended rapid viral response (undetectable HCV-RNA at weeks 4 and 12 of triple therapy). Treatment length is mainly based on the stage of fibrosis and prior response to pegylated interferon and ribavirin. Thus, in both treatment-naïve patients and patients with recurrence after pegylated interferon therapy, the duration of treatment is 24 or 48 weeks (unless cirrhosis is present), depending on the presence of extended rapid viral response, while in cirrhotic patients and null responders, treatment length is 48 weeks. The main adverse effects of telaprevir therapy are anemia and skin rash. If these effects occur, the main measures that should be adopted are reduction of the ribavirin dose in anemia, and close monitoring and treatment cessation in skin rash, depending on its spread and severity.
To describe the frequency and the characteristics of hepatocellular carcinoma (HCC) cases that appeared in HIV/hepatitis C virus (HCV)-coinfected patients with previous sustained virological response ...(SVR) and to compare these cases to those diagnosed in patients without SVR.
All HIV/HCV-coinfected patients diagnosed with HCC in 26 hospitals in Spain before 31 December 2012 were analyzed. Comparisons between cases diagnosed in patients with and without previous SVR were made.
One hundred and sixty-seven HIV/HCV-coinfected patients were diagnosed with HCC in the participant hospitals. Sixty-five (39%) of them had been previously treated against HCV. In 13 cases, HCC was diagnosed after achieving consecution of SVR, accounting for 7.8% of the overall cases. The median (Q1-Q3) elapsed time from SVR to diagnosis of HCC was 28 (20-39) months. HCC was multicentric and was complicated with portal thrombosis in nine and six patients, respectively. Comparisons with HCC cases diagnosed in patients without previous SVR only yielded a significantly higher proportion of genotype 3 infection 10 (83%) out of 13 cases versus 34 (32%) out of 107; P = 0.001). The median (Q1-Q3) survival of HCC was 3 (1-39) months among cases developed in patients with previous SVR, whereas it was 6 (2-20) months in the remaining individuals (P = 0.7).
HIV/HCV-coinfected patients with previous SVR may develop HCC in the mid term and long term. These cases account for a significant proportion of the total cases of HCC in this setting. Our findings reinforce the need to continue surveillance of HCC with ultrasound examinations in patients with cirrhosis who respond to anti-HCV therapy.
Although two pegylated interferons (Peg-IFN) are available to treat chronic hepatitis C virus (HCV) infection, no head-to-head comparative studies have been published. We aim to compare the efficacy ...and safety of PEG IFN alfa-2b (PEG 2b) versus PEG IFN alfa-2a (PEG 2a), plus ribavirin (RBV). A prospective, randomized, multi-center, open-label clinical trial including 182 human immunodeficiency virus (HIV)-hepatitis C virus (HCV) patients naïve for HCV therapy was performed. Patients were assigned to PEG 2b (80-150 mug/week; n = 96) or PEG 2a (180 mug/week; n = 86), plus RBV (800-1200 mg/day) for 48 weeks. The primary endpoint was sustained virological response (SVR: negative HCV-RNA 24 weeks after completion of treatment). At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 or corrected 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P = 0.65). Among genotypes 1 or corrected 4, SVRs were 28% versus 32% (P = 0.67) and 62% versus 71% (P = 0.6) in genotypes 2 or corrected 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; >or=2 log reduction from baseline or negative HCV-RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P = 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P = 0.47).
In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety.
To provide detailed information about the natural history of HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis.
Prospective cohort including 340 HIV-HCV-coinfected patients with ...compensated (n = 248) or decompensated (n = 92) cirrhosis. We evaluated predictors of survival and of first hepatic decompensation.
The mortality rate for patients with decompensated and compensated cirrhosis was 27.14 deaths per 100 person-years 95% confidence interval (CI) 18.93-35.35 and 3.98 deaths per 100 person-years (95% CI 2.42-5.54), respectively. Rate of first hepatic decompensation in patients with compensated cirrhosis was 4.62 per 100 persons-years (95% CI 2.91-6.33). In the complete cohort, permanent HAART interruption during follow-up, CD4 cell count nadir and baseline Child-Pugh score (CPS) B or C were significantly associated with shorter survival. In patients with compensated cirrhosis factors significantly associated with decreased survival were having the first hepatic decompensation during follow-up, permanent HAART discontinuation, and CPS B and C at baseline. For patients with compensated cirrhosis, time since diagnosis of HCV infection, CPS B and C and permanent HAART discontinuation were significantly associated with the risk of first hepatic decompensation. Sustained viral response to anti-HCV therapy was not independently associated with better survival in patients with compensated cirrhosis.
HIV-HCV-coinfected patients with cirrhosis have a relatively good 3-year survival (87%). In contrast, 2-year survival of patients with decompensated liver cirrhosis is only 50%. Three-year survival was mostly impacted by liver-related factors and HAART maintenance.
OBJECTIVE:To compare the prognostic performance of liver biopsy with that of liver stiffness measurement (LSM) to predict survival and liver decompensations among HIV/hepatitis C virus ...(HCV)-coinfected patients.
DESIGN:Retrospective cohort study.
METHODS:Cohort of 297 HIV/HCV-coinfected patients, who underwent a liver biopsy and LSM separated by 12 months or less, followed in 10 Spanish tertiary care centers from December 2005 to December 2011 (median follow-up, 5 years; interquartile range, 4.2–5.4 years). Liver biopsies were staged following the Scheuerʼs score. LSM was obtained by hepatic transient elastometry. A survival analysis was carried out and the integrated discrimination improvement was computed to compare the ability of the survival models to predict outcomes. The incidence of death from any cause and of development of the first decompensation of cirrhosis was calculated.
RESULTS:Overall mortality rate was 1.63 95% confidence interval (CI) 1.06–2.49 per 100 person-years. The adjusted hazard ratio AHR (95% CI) of baseline fibrosis (per stage of fibrosis) was 1.52 (1.08–2.15, P = 0.017) and of LSM (per 5 kPa increase) 1.28 (1.12–1.46, P < 0.001). LSM including models yielded a performance 3.9% better than the liver biopsy-based models (P = 0.072). For the prediction of liver decompensations, the AHR (95% CI) of baseline fibrosis by liver biopsy (per stage of fibrosis) was 1.67 (1.15–2.43, P = 0.007) and of LSM (per 5 kPa increase) 1.37 (1.21–1.54, P < 0.001). LSM-based models yielded a performance 8.4% better than the liver biopsy-based models (P = 0.045).
CONCLUSION:LSM-based prediction achieves a similar yield than liver biopsy-based models to predict overall mortality in HIV/HCV-coinfected patients. Models including LSM could predict better liver decompensations than liver biopsy.
Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatits C virus—specific treatment in human immunodeficiency virus (HIV)—uninfected and —infected ...patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.
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