1,721,056 research outputs found
Decrease in Incidence Rate of Hospitalizations Due to AIDS-Defining Conditions but Not to Non-AIDS Conditions in PLWHIV on cART in 2008-2018 in Italy
Full text linkWe aimed to describe the change in the incidence and causes of hospitalization between 2008 and 2018 among persons living with HIV (PLWHIV) who started antiretroviral therapy (ART) from 2008 onwards in Italy
Incidence, timing, and determinants of bacterial pneumonia among HIV-infected patients: data from the ICONA Foundation Cohort
No full textBACKGROUND:
The aim of the study was to evaluate incidence and determinants of bacterial pneumonia (BP) after starting combination antiretroviral therapy (cART) in the Italian Cohort of Antiretroviral-Naive Patients.
METHODS:
Patients free from BP at cART initiation enrolled between 1996 and 2011 were analyzed. Kaplan-Meier curves were calculated to estimate the time to the first episode of BP; uni- and multivariable Cox proportional hazard models, with time-updated covariates, were applied to identify the risk factors of the first episode of BP.
RESULTS:
Four thousand nine hundred forty-two patients were followed for a median of 63.7 months (interquartile range: 23.6, 106.7); 73% were men, median age 36 years (interquartile range: 32, 42), 35% hepatitis C virus antibody positive, 28% smokers, 15% with an AIDS diagnosis (not BP) before cART, 46% with nadir CD4+ T-cell count ≤200 cells per microliter. During 27,569 person years, 137 patients developed 156 BPs, for a crude incidence of 5.66 [95% confidence interval (CI): 4.81 to 6.62] per 1000 person years. The probabilities of first BP at 3, 5, 10, and 14 years from cART initiation were 2.0% ± 0.22%, 2.9% ± 0.28%, 4.3% ± 0.42%, and 5.7% ± 0.75%, respectively. The occurrence of a first BP was associated with low nadir CD4+ [hazard ratios (HR) (per 100 cells/μL higher) = 0.86, 95% CI: 0.79 to 0.94], low current CD4 [HR (per 100 cells/μL higher) = 0.88, 95% CI: 0.84 to 0.92], high CD8+ [HR (per 100 cells/μL higher) = 1.02, 95% CI: 1.01 to 1.03], low hemoglobin [HR (per g/dL higher) = 0.74, 95% CI: 0.71 to 0.78], and unfavorable virological outcome [HR (HIV-RNA >50 vs <50 copies/mL) = 1.29, 95% CI: 1.04 to 1.60] in addition to older age, male gender, non-Italian nationality, smoking, and longer time to cART initiation.
CONCLUSIONS:
BP is an infrequent clinical event in the cART era and is associated with traditional risk factors,viroimmunological failure to cART, and low hemoglobin
Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients.
No full text“CD4 exploders” and “CD4 peak achievers” under ART in a large Italian cohort of HIV-infected subjects
No full textBackground: 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
Discontinuation of initial antiretroviral therapy in clinical practice: Moving toward individualized therapy
Full text linkackground: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of ≥1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4+cell (P = 0.011), and higher lymphocyte T CD8+cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity
Pregnancy outcomes among ART-naive and ART-experienced HIV-positive women: data from the ICONA foundation study group, years 1997-2013
No full textBACKGROUND: We analyzed antiretroviral therapy (ART) regimens and pregnancy outcomes in naive and ART-experienced HIV-positive women from Italian Cohort Naive Antiretrovirals cohort and investigated frequency and predictors of detectable viral load (VL) at delivery.
METHODS: All pregnancies resulting in live births were included. Based on ART at the beginning of pregnancy, pregnancies were allocated either to the ART-naive or ART-experienced group. Analyses were stratified according to calendar periods. Multivariate logistic regression was used to describe predictors of detectable VL at delivery.
RESULTS: One hundred fifty-eight of 2862 women experienced 169 pregnancies (88 in naives and 81 in 70 ART-experienced women). ART regimens varied according to calendar periods; mono-dual combination regimens progressively decreased over time (P value for trend 50 copies per milliliter at pregnancy ascertainment (adjusted odds ratio: 7.1, 95% confidence interval: 1.9 to 33.3, P = 0.006). Nevertheless, no cases of vertical transmission were diagnosed. Preterm birth rate of 17.3% (11.9% vs 22.6% naive and ART experienced, P = 0.1) was reported; this was not associated with ART duration or protease inhibitor-including regimens; 27.2% of infants had <2500 g birth weight.
CONCLUSIONS: Antiretroviral regimens prescribed during pregnancy changed over time according to guidelines. Although undetectable VL was not always achieved, no vertical transmission occurred; preterm delivery and low birth weight occurred in some cases and still remain key issues
Risk of developing specific AIDS-defining illnesses in patients coinefcted with HIV and hepatitis C virus with or without liver cirrhosis
No full textBACKGROUND: There are few data concerning the risk of specific opportunistic diseases in patients with and without hepatitis C virus (HCV) infection. We evaluated the correlation between the occurrence of different AIDS-defining illnesses (ADIs) and chronic HCV infection or HCV-related liver cirrhosis in a large Italian cohort of human immunodeficiency virus (HIV)-infected subjects. METHODS: Subjects were stratified into 2 groups: patients without HCV coinfection and with persistently normal aminotransferase levels and patients with HCV coinfection. The patients with HCV coinfection were stratified according to the diagnosis of liver cirrhosis. The incidences of new ADIs were calculated as the number of events per 1000 person-years of follow-up. The rates in the 2 groups were compared using a Poisson regression model adjusted for potential confounders. RESULTS: We observed a total of 496 ADIs among 5397 patients with 25,105 person-years of follow-up (50% tested positive for HCV). HCV coinfection was associated with increased risk of developing an ADI (adjusted relative rate [ARR], 2.61; 95% confidence interval [CI], 1.88-3.61), specifically bacterial infection (ARR, 3.15; 95% CI, 1.76-5.67), HIV-related disease (ARR, 2.68; 95% CI, 1.03-6.97), and mycotic disease (ARR, 3.87; 95% CI, 2.28-6.59) but not non-Hodgkin lymphoma (ARR, 0.88; 95% CI, 0.22-3.48). The rate of mycotic infection, bacterial infection, toxoplasmosis, and HIV-related ADI among patients with cirrhosis were significantly higher than that among HIV-monoinfected patients, and the risk was greater than that estimated for HCV antibody-positive patients without cirrhosis. CONCLUSIONS: HIV-related bacterial and mycotic infections are strongly associated with positive HCV serostatus and HCV-related cirrhosis. Clinicians should take into account these data when making decisions on initiation of antiretroviral therapy for HCV-coinfected individuals
Liver enzyme elevation during darunavir-based antiretroviral treatment in HIV-1-infected patients with or without hepatitis C co-infection : data from the ICONA Foundation cohort HIV Clinical Trials
No full textObjectives: To investigate differences in liver enzyme elevation (LEE) between HIV-infected patients with and without HCV coinfection who start a darunavir/ritonavir-containing regimen. Methods: HIV-infected patients enrolled in the Italian Cohort of Naive to Antiretrovirals (ICONA) Foundation Study were included if they started darunavir/ritonavir for the first time. Patients were classified as not HCV coinfected, HCV active coinfected (HCV RNA positive), and HCV nonactive coinfected (HCV-Ab positive/HCV RNA negative). Time to LEE endpoint was defined using the ACTG toxicity scale, based on changes relative to baseline. Kaplan-Meier was used to estimate 1-year and 2-year probability of LEE. The incidence rate ratios (IRRs) of LEEs were estimated until the last follow-up (intention-to-treat analysis [ITT]) and up to darunavir/ritonavir discontinuation (on-treatment analysis [OT]). Results: Overall, 703 patients were included. Ninety-one were HCV-Ab positive; of those, 68 (9.7%) had active HCV coinfection. In 879 person-years of follow-up, 101 LEEs occurred (ITT). No severe hepatotoxicity event was registered in active HCV coinfected patients. HCV active coinfection was predictive of LEE in the overall population (OT: adjusted incidence rate ratio (IRR), 2.25; 95% CI, 0.70-7.24; P = .17; ITT: adjusted IRR, 3.62; 95% CI, 1.67-7.83; P < .001) and in naive patients (OT: adjusted IRR, 6.29; 95% CI, 2.54-15.55; P = .00; ITT: adjusted IRR, 3.87; 95% CI, 0.99-15.16; P = .05). Conclusions: No grade 3-4 LEEs occurred in HCV active coinfected patients. HCV active coinfected patients experienced low grade LEEs more frequently than HCV-Ab negative patients. Darunavir/ritonavir seems to be safe whatever the HCV status, when liver enzymes are carefully monitored
Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus
Full text linkObjective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 < 1.45, 26.4% 1.45-3.25 and 7.7% > 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to < 1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 > 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4> 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART
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