Evolution of glomerular filtration rate in HIV‐infected,HIV–HBV‐coinfected and HBV‐infected patients receiving tenofovir disoproxil fumarate

We aimed to compare the evolution of estimated glomerular filtration rate (eGFR) in HIV‐, HIV–HBV‐ and HBV‐infected patients treated with tenofovir disoproxil fumarate (TDF). Three groups of patients receiving TDF > 12 months were recruited: 194 HIV‐infected patients, 85 HIV–HBV‐coinfected patients and 50 HBV‐infected patients. eGFR was estimated using the Modification of the Diet in Renal Disease (MDRD) equation. Multivariate regression models were constructed to estimate factors associated with eGFR decrease from baseline. A total of 329 patients were studied. Median follow‐up was 2.7 years. Median eGFR decrease was ?4.9 (?16.6 to +7.2) mL/min/1.73 m². After multivariate stepwise regression analysis, age (P = 0.0002), non‐African origin (P < 0.0001), baseline eGFR (P < 0.0001) and TDF duration (P = 0.02) were associated with eGFR decrease in the whole population, while hypertension, diabetes and type of infection were not. Age (P < 0.0001), non‐African origin (P = 0.0004), baseline eGFR (P < 0.0001) and TDF duration (P = 0.007) remained associated with eGFR decline in HIV and HIV–HBV‐infected patients, while other variables including HIV risk factor, CDC stage, CD4 and HIV‐RNA levels were not. Age (P = 0.03), non‐African origin (P = 0.004), baseline eGFR (P < 0.0001) and baseline HBV–DNA > 2000 IU/mL (P = 0.04) were associated with eGFR decline in HBV and HIV–HBV‐infected patients, while other variables including HBV risk factor and fibrosis stage were not. Estimated glomerular filtration rate decline under TDF therapy appears mainly associated with older age, non‐African origin, higher baseline eGFR and longer TDF administration but not with the type of viral infection. Regular follow‐up of renal function, especially tubular function is recommended during TDF therapy.     

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.     

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.     

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.     

Peripheral T‐cell lymphoma in HIV‐infected patients: a study of 17 cases in the combination antiretroviral therapy era

Most cases of human immunodeficiency virus (HIV)‐associated non‐Hodgkin Lymphoma (NHL) are of B‐cell origin; T‐cell NHLs are rarely reported. Within a single centre prospective cohort of 370 HIV‐NHL, 17 (5%) were of T‐cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 10⁹/l and 41% had undetectable plasma HIV‐RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full‐dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow‐up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity.