Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

A case-control study of non-AIDS-defining cancers in a prospective cohort of HIV-infected patients. / Estudio caso-control de tumores no definitorios de sida en una cohorte prospectiva de pacientes infectados por el VIH.

INTRODUCTION: We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. METHODS: All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. RESULTS: Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality. CONCLUSIONS: Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

[Cross sectional study of comorbidities and concomitant medications in a cohort of human immunodeficiency virus-infected patients]. / Estudio transversal de comorbilidades y medicaciones concomitantes en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana.

AIM: To assess the prevalence of comorbidities, concomitant therapies and adverse effects associated with the medication in a cohort of patients with HIV infection. DESIGN: Multicentre cross-sectional study. SETTINGS: Infectious Diseases or Internal Medicine outpatient Clinics of 3 hospitals in the Basque Country. PARTICIPANTS: During a 3 month period, patients with the following inclusion criteria were randomly selected: HIV infection, age>18years, antiretroviral treatment (ART) for at least 6months, and no changes in ART in the previous 4weeks. A total of 224 patients (of the 225 expected) were included. MEASUREMENTS: Data were collected using a form, and include, epidemiological and anthropometric data, data related to HIV infection, comorbidities, current therapies, and adverse effects. RESULTS: Of the 224 patients, 95.5% had at least one comorbidity, the most common being HCV infection (51.3%), dyslipidaemia (37.9%), diabetes mellitus or impaired fasting glucose (21.9%), and hypertension (21.9%). A total of 155 patients (69.2%) were taking concomitant medication: anxiolytics (21.4%), antihypertensives (19.6%), proton pump inhibitors (17.9%), statins (17%), and antidepressants (16.5%). Adverse effects (AE) were observed in 62.9% of subjects, the most common being, changes in body fat distribution (32.6%) and gastrointestinal (24.1%). CONCLUSIONS: Patients with HIV infection are getting older, with more comorbidities, with very frequent use of concomitant treatments, and high number of adverse effects. This requires a multidisciplinary approach and a coordinated effort within the Primary Care setting.

Real-life experience with sorafenib for the treatment of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To report the real-life results of sorafenib use in a cohort of HIV-infected patients with hepatocellular carcinoma (HCC). METHODS: The GEHEP-002 cohort (ClinicalTrials.gov ID: NCT02785835) has recruited 302 HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. RIS-HEP12 study included 44 (14%) cases that have received at least one dose of sorafenib. The overall survival after the start of treatment was the main efficacy outcome. Permanent discontinuation due to adverse events was the primary safety end point. RESULTS: Reasons for sorafenib use are HCC recurrence after previous curative therapy (n = 7), progression following transarterial chemoembolization (n = 6) and first treatment against HCC (n = 31). Nineteen (43%) patients harbored Child-Pugh B cirrhosis. Barcelona-Clinic Liver Cancer stage was A 3 (7%), B 6 (14%), C 30 (68%) and D 5 (11%). All patients were on antiretroviral therapy (ART). The median (Q1-Q3) duration of sorafenib treatment was 70 (31-158) days. Median survival was 7.2 months, whereas the median (Q1-Q3) duration of overall survival after the start of treatment was 4 (2-9.7) months. Twenty-six (59%) patients had any grade adverse events and 19 (43%) suffered a decompensation. Discontinuation due to adverse events occurred in 17 (38.6%) patients. There were no modifications or discontinuations of ART. CD4 cell counts and HIV viral load remained stable. CONCLUSION: The efficacy of sorafenib under real-life conditions in HIV-infected patients seems lower than that reported in the registration clinical trial. On the contrary, the tolerability of sorafenib appears to be similar to what is seen in patients without HIV infection. Sorafenib does not seem to modify the efficacy of ART.

HIV/hepatitis C virus-coinfected patients who achieved sustained virological response are still at risk of developing hepatocellular carcinoma.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Long-term effectiveness and safety outcomes in HIV-1-infected patients after a median time of 6 years on nevirapine.

To report long-term data on safety and effectiveness of antiretroviral regimens, including nevirapine. HIV-1-infected patients who received nevirapine-based approaches for at least 4 years were identified in the databases of five centers and included in a retrospective cohort study. Data collected included plasma HIV-RNA (viral load) and CD4+ T-cell counts, lipid and liver function tests, at baseline, 2-year and > 4-year time points. Hepatitis C virus (HCV) coinfection, adverse events, and reasons for using nevirapine were also recorded. Two hundred and twenty-nine patients (139 males/90 females) were included. The mean age was 37 years (range 20-59). Most patients (n = 124; 54%) were former intravenous drug users. One hundred and thirty-five of the patients (59%) were coinfected with HCV. Median time on nevirapine was 72.6 months. The main reasons for nevirapine use included: second- or third-line therapy (39%), simplification of therapy (29%), first-line therapy (18%) and efavirenz intolerance (9%). LDL cholesterol and triglycerides decreased during the >4-year follow-up (135 mg/dl to 109 mg/dl, p = 0.04; and 216 mg/dl to 153 mg/dl, p<0.01, respectively), and HDL cholesterol increased from 48 mg/dl at baseline to 62 mg/dl (p<0.01). Liver enzymes remained without significant changes during follow-up. The reported follow-up pattern of laboratory tests was also found in the subset of HCV-coinfected patients, where men and women were compared and patients with a CD4+ cell count cut-off value of 250/mm(3) were stratified. Mean CD4+ T-cell counts increased from 439/mm(3) at baseline to 628/mm(3) at the last available visit (p<0.001). Ninety-four per cent (172 out of 184) of patients who remained on nevirapine-based therapy at last visit maintained viral load values below the limit of detection (<50 copies/ml). Throughout the follow-up nevirapine was stopped or withdrawn in 43 patients due to virological failure (n = 17), toxicity (n = 5), therapy interruption (n = 3), death (n = 2), dyslipidemia (n = 1), simplification (n = 1) or unknown reasons (n = 14). Adverse events were reported in 40 patients but none was directly attributed to nevirapine. Nevirapine-based antiretroviral therapy provides sustained immunological and virological effectiveness over a more than 4-year treatment period as well as a beneficial lipid metabolic profile and a favorable safety profile, even in HCV-coinfected patients and women with CD4+ cell counts above 250/mm(3). The study data support a nevirapine-based approach as a suitable long-term strategy in the HIV-1-infected population.

Characteristics and outcome of AIDS-related Hodgkin lymphoma before and after the introduction of highly active antiretroviral therapy.

OBJECTIVES: We analyzed survival, therapeutic response, and prognostic factors in patients with HIV-related Hodgkin lymphoma (HL) treated or not with highly active antiretroviral therapy (HAART). METHODS: This study included 104 patients with HL, treated (n = 83) or not (n = 21) with HAART. Outcomes and prognostic factors of complete remission (CR), overall survival (OS), and disease-free survival (DFS) were assessed by an intention-to-treat analysis of all patients who received at least 1 chemotherapy course. RESULTS: No differences were found between groups at baseline in the specific characteristics of HIV and HL. The proportion of patients receiving appropriate-for-stage therapy for HL was similar for both groups. The CR rates in the HAART (-) and HAART (+) groups were 14 (70%) of 20 versus 71 (91%) of 78 (P = 0.023). The median OS in the HAART (-) group was 39 months (95% confidence interval [CI]: 0 to 89) and was not reached in the HAART (+) group (P = 0.0089). The median DFS in the HAART (-) group was 85 months (95% CI: 73 to 97) and was not reached in the HAART (+) group (P = 0.129). Factors independently associated with CR by logistic regression analysis were appropriate-for-stage therapy of HL, HAART, and baseline CD4 count > or =100 cells/microL. CR was the only factor independently associated with OS by Cox regression analysis. CONCLUSIONS: The achievement of CR was independently associated with appropriate-for-stage therapy for HL, with HAART, and with a baseline CD4 count > or =100 cells/microL. The only variable independently associated with OS was the achievement of CR.

Prognosis of AIDS-related systemic non-Hodgkin lymphoma treated with chemotherapy and highly active antiretroviral therapy depends exclusively on tumor-related factors.

OBJECTIVES: To assess complete remission (CR) and survival in patients with systemic AIDS-related non-Hodgkin lymphoma (ARL) receiving highly active antiretroviral therapy (HAART). METHODS: We analyzed the Grupo de Estudio del SIDA register of systemic ARL, which started in Jan 1994, to collect cases diagnosed at 15 institutions prospectively and with active follow-up every 6 months. The date of censorship for this study was March 2005. RESULTS: During the study period, 210 consecutive patients were diagnosed with ARL, with a median age 39 of years, 75.7% of whom were male, and with a median baseline CD4 count of 160 cells/microL. Histologic subtypes were diffuse large B-cell lymphoma (DLCL; n = 153 [72.9%]), Burkitt and atypical Burkitt/Burkitt-like lymphoma (BL; n = 40 [19.0%]), T-cell lymphoma (TC; n = 8 [3.8%]), and miscellaneous (n = 9 [4.3%]). Chemotherapy with or without other modalities was administered to 186 (88.6%) patients. In an intent-to-treat analysis of 184 patients who received at least 1 chemotherapy course with adequate follow-up to assess their response, 119 (64.7%) achieved CR, and the median length of survival (Kaplan-Meier analysis) was 52 months (95% confidence interval [CI]: 23 to 82 months). Factors independently associated with CR were histologic subtype and International Prognostic Index (IPI) score. Factors independently associated with improved overall length of survival (OS) were CR, low IPI score, and histologic subtype. The single factor independently associated with disease-free survival was Ann Arbor stage. CONCLUSIONS: In patients with ARL treated with HAART, CR was associated exclusively with tumor-related factors. The CR rate was poorer in patients with BL and TC subtypes and was inversely correlated with IPI score. OS was independently associated with CR, IPI score, and the histologic subtype.

Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy.

We analyzed survival rates, neurologic function, and prognostic factors for 118 consecutive patients with acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) in 11 hospitals throughout Spain. Seventy-five patients (63.6%) remained alive for a median of 114 weeks (2.2 years) after diagnosis of PML. Neurologic function of the survivors was categorized as cure or improvement in 33, stabilization or worsening in 40, and unknown in 2. The baseline CD4+ cell count was the only variable found with prognostic significance. The odds ratio of death was 2.71 (95% confidence interval, 1.19-6.15) for patients with CD4+ cell counts of <100 cells/microL, compared with patients who had CD4+ cell counts of > or =100 cells/microL. One-third of patients with PML died despite receipt of HAART; neurologic function improved in approximately one-half of the survivors. A CD4+ cell count of <100 cells/microL was associated with higher mortality.