Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co‐infected patients

Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co‐infected patients. HCV viral load and 50 biomarkers were analysed at baseline and 27 time points during pegylated interferon‐alpha and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co‐infected patients. We evaluated biomarker changes from baseline for each time point and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL‐1α, IL‐12p40, IL‐1RA, IP‐10, MIG, MIP‐1α/1β, HGF, sCD40L, TRAIL and leptin increased in the first day. IL‐12p70, IL‐17A, IL‐10, GROα, IL‐8, MCP‐3, IL‐4 and M‐CSF peaked later during week 1. IL‐1α, HGF, IP‐10, MIP‐1α, TRAIL, sCD40L, IL‐10, IL‐12p70, MCP‐3, FGFb, ENA‐78, TGF‐β, IL‐2, IFN‐γ, IL‐6, IL‐15, IL‐7 and PDGF‐BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virologic response. ENA‐78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.     

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.     

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.     

Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients

Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co‐infections. Seventy‐eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV‐HCV co‐infected, HCV mono‐infected and uninfected). The BMD was measured by dual energy X‐ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F‐BMD reduction in all the three groups, whereas L‐BMD was significantly lower in co‐infected patients (P < 0.05). The clinical score was higher in co‐infected (P < 0.002) and mono‐infected (P < 0.006). The radiological score was higher in mono‐infected than in the other two groups (P < 0.001). Overall 25‐hydroxyvitamin D (25‐OH Vit D) was reduced (87%). Bone‐specific alkaline phosphatase (b‐ALP) and telopeptide were increased in co‐infected (P < 0.001 and P < 0.01) and mono‐infected (P < 0.001 and P < 0.02). The result of the homogeneous F‐BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L‐BMD in co‐infected and the increase of b‐ALP and telopeptide in co‐infected and mono‐infected groups suggest faster bone metabolism in case of infections.     

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.