Morbidity and mortality in ageing HIV‐infected haemophilia patients

Over 25 years of follow‐up is now available for HIV‐infected haemophilia patients. The aim of this study was to retrospectively asses the morbidity and mortality of HIV infection and the effects of HAART in these patients. Data on HIV infection, its treatment and all types of comorbidity were collected from medical records of all 60 HIV‐positive haemophilia patients who were treated at the Van Creveldkliniek since 1980 and compared with data from 152 HIV‐negative patients with severe haemophilia and the general age‐matched male population. AIDS developed in 27 patients (45%), while 31 patients died (52%). Death was solely or partially AIDS‐related in 71%. Development of AIDS and AIDS‐related deaths declined strongly after the introduction of HAART. Only one major ischaemic cardiovascular event occurred in our study population. Of the 27 patients who were still treated at our clinic in 2010, 25 (93%) were on HAART. They had more often hypertension and diabetes, but less often overweight and obesity and lower cholesterol levels than the general population. The occurrence of spontaneous intracranial bleeding was higher in HIV‐positive haemophilia patients on HAART than in HIV‐negative patients with severe haemophilia (16.6 vs. 1.2 per 1000 patient years). Since the introduction of HAART, the impact of HIV infection on morbidity and survival has decreased. The increased prevalences of hypertension and diabetes, however, warrant regular screening. HIV‐positive haemophilia patients on HAART appear to have an increased risk of spontaneous intracranial bleeding.     

More improvement than progression of liver fibrosis following antiretroviral therapy in a longitudinal cohort of HIV‐infected patients with or without HBV and HCV co‐infections

We examined the effect of combination antiretroviral therapy (cART) on liver fibrosis among HIV‐infected patients with or without hepatitis B (HBV) or C virus (HCV) co‐infection. This was a retrospective cohort study of HIV‐infected patients receiving cART during 2004‐2016. Liver fibrosis was assessed using Fibrosis‐4 (FIB‐4) score with three classifications: Class 1, <1.45; Class 2, 1.45‐3.25; Class 3, >3.25. Of 3900 participants, 68.6% were HIV mono‐infected, 5.3% were HIV/HBV co‐infected, 23.8% were HIV/HCV co‐infected and 2.3% were HIV/HBV/HCV co‐infected. Participants received follow‐up treatment (median was 3.3 years). Improvement to a lower class was observed in Class 2 (52.6%) and Class 3 (74.2%), respectively. Progression to a higher class was observed in 12.8% and 5.0% in Class 1 and Class 2, respectively, and with a median time of 5.7 months. For improvement to lower classes, older age, male, Dai ethnicity, injection drug use, HCV co‐infection and tenofovir for treatment were negative predictors, but in Class 3 of FIB‐4 and time‐updated increases in CD4 count from baseline were positive predictors. For progression to higher classes, older age, male, Jingpo ethnicity and HCV co‐infection were positive predictors, while baseline CD4 count and in Class 2 of FIB‐4 were negative predictors. Improvement to lower class linked with decreased mortality risk among patients in Class 3. Early cART initiation for HIV‐infected patients with and without hepatitis co‐infections may mitigate or slow down some of liver fibrosis, but special attention should be given to those who are older, male, co‐infected with HCV.     

Intensification with pegylated interferon during treatment with tenofovir in HIV–hepatitis B virus co‐infected patients

In hepatitis B “e” antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono‐infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long‐term effect of adding PegIFN to tenofovir (TDF)‐containing antiretroviral therapy on seroclearance in HBeAg‐positive patients co‐infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1‐year PegIFN intensification during TDF‐containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time‐dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed‐effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4–59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log₁₀IU/mL, respectively (P>.5 between groups). Median follow‐up was 33.4 months (IQR=19.0–36.3). During intensification, faster average declines of qHBeAg (?0.066 vs ?0.027 PEIU/mL/month, P=.001) and qHBsAg (?0.049 vs ?0.026 log₁₀IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg‐positive co‐infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.     

Effect of hepatitis C virus on immunological and virological responses in HIV‐infected patients initiating highly active antiretroviral therapy: a meta‐analysis

Co‐infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta‐analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co‐infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta‐analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co‐infected subjects after 3–12 months on HAART was 34.86 cells/mm³ [95% confidence interval (CI): 16.82–52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm³ (38.97, 95% CI: 20.00–57.93) and attenuated 2 years later (13.43, 95% CI: 0.83–26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co‐infected patients vs those with HIV alone: 0.99, 95% CI: 0.91–1.07). The bivariate meta‐analytic method confirmed the results of the univariate approaches. This meta‐analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co‐infection seems to be justified.     

Incidence and risk factors for incomplete HBV DNA suppression in HIV/HBV‐co‐infected patients initiating tenofovir‐based therapy

Suppression of hepatitis B virus (HBV)‐DNA to undetectable levels is an important goal for HIV/HBV‐co‐infected patients receiving anti‐HBV‐active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir‐based ART. We performed a cohort study among tenofovir‐treated HIV/HBV‐co‐infected patients. Patients had HBV viraemia, initiated tenofovir‐based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46–63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1–1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19–5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir‐treated HIV/HBV‐co‐infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.     

Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV‐positive patients

Patients infected with HIV are at increased risk for cardiovascular disease despite successful antiretroviral therapy. Likewise, chronic hepatitis C virus (HCV) infection is associated with extrahepatic complications, including cardiovascular disease. However the risk of cardiovascular disease has not been formally examined in HIV/HCV‐coinfected patients. A retrospective study was carried out to assess the influence of HCV coinfection on the risk of cardiovascular events in a large cohort of HIV‐infected patients recruited since year 2004. A composite event of cardiovascular disease was used as an endpoint, including myocardial infarction, angina pectoris, stroke or death due to any of them. A total of 1136 patients (567 HIV‐monoinfected, 70 HCV‐monoinfected and 499 HIV/HCV‐coinfected) were analysed. Mean age was 42.7 years, 79% were males, and 46% were former injection drug users. Over a mean follow‐up of 79.4 ± 21 months, 3 patients died due to cardiovascular disease, whereas 29 suffered a first episode of coronary ischaemia or stroke. HIV/HCV‐coinfected patients had a greater incidence of cardiovascular disease events and/or death than HIV‐monoinfected individuals (4% vs 1.2%, P = 0.004) and HCV‐monoinfected persons (4% vs 1.4%, P = 0.5). After adjusting for demographics, virological parameters and classical cardiovascular disease risk factors (smoking, hypertension, diabetes, high LDL cholesterol), both HIV/HCV coinfection (HR 2.91; CI 95%: 1.19–7.12; P = 0.02) and hypertension (HR 3.65; CI 95%: 1.34–9.94; P = 0.01) were independently associated with cardiovascular disease events and/or death in HIV‐infected patients. Chronic hepatitis C and hypertension are independently associated with increased cardiovascular disease risk in HIV‐infected patients. Therefore, treatment of chronic hepatitis C should be prioritized in HIV/HCV‐coinfected patients regardless of any liver fibrosis staging.