Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1

Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15–2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00–2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.

Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease

Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n=60) and telbivudine-replacement (n=60) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p<0.001). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.

Hepatitis B (HBV) Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Lenalidomide Containing Regimens: A Single Center Experience

Introduction: Reactivation of HBV refers to an increase in hepatitis B virus replication in a patient with inactive or resolved HBV. Reactivation of HBV replication has been reported in 20% to 50% of untreated HBV carriers undergoing immunosuppressive or cancer chemotherapy. Bortezomib has been reported to induce viral reactivation(5.9% HBV reactivation rate)(Liu et al). Herein, we aim to present the rate and fate of HBV reactivation among myeloma patients who have received lenalidomide containing protocols. Patients and Methods: We have evaluated 142 MM patients diagnosed between 2003-2014 who received lenalidomide during their treatment schedules whether for induction, relapse or post-induction maintenance treatment. 92 patients received 25 mg/day lenalidomide with Dexamethasone, 50 received at 10 mg/day as single agent. To be eligible for the analysis a minimum three months duration of treatment and no active hepatitis were required. Hepatitis B serology is rechecked before autologous peripheral stem cell transplantation and if liver enzyme abnormality occured. The hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (AntiHBe) are detected by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers are determined by quantitative PCR. Results: The median age of 142 MM patients was 56 (range, 42-77). 79 of patients were male (56%). ISS scores at diagnosis were as follows: ISS I/II/III: 51 (36%),57 (40%), 34 (24%). At the initiation of treatment 11 patients had negative HbsAg, positive AntiHBe, AntiHBcIgG, AntiHBs with normal liver function tests. Lamivudine prophylaxis was administered to these naturally immune 11 patients. One of these eleven patients and five patients who had no prior viral exposure had hepatitis B reactivation (4.2%) (Table). All these patients had hypogamaglobulinemia at diagnosis and had received bortezomib prior to lenalidomide. One patient had a history of dialysis. Four patients had received dexamethasone treatment in addition to lenalidomide. After treatment of tenofovir, HBV DNA titers decreased in all and disappeared among three of the six patients. Lenalidomide treatment was interrupted in three of the patients due to progression of disease. One patient who received a second stem cell transplantation for a secondary refractory disease had a progression to cirrhosis following high dose Melphalan. Conclusion: In the current retrospective analysis we observed reactivation of hepatitis in 4.2% of patients who happened to have high ISS scores and were heavily treated previously. Only one patient had activation under prophylaxis. Lenalidomide can be associated with a low reactivation rate of HBV. Hepatitis B reactivation was detected more with lenalidomide and dexamethasone treated patients. The reactivation rate observed in this retrospective analysis is lower than those published previously and may account for the immune modulation effects of lenalidomide and close follow-up. Table 1. Patient Characteristics (CR: Complete Response, PR: Partial Response, PD: Progressive Disease, VGPR: Very Good Partial Response) Patient Age (years)/MM type/ISS Treatment lines/Bortezomib prior/Lamivudine prophylaxis Hepatitis B markers at diagnosis Hepatitis B markers after revlimid treatment Treatment/Time to reactivation after lenalidomide (months) OS (months)/Status of disease 56/Lambda/2 3/+/- HBsAg-, HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg, AntiHBc+,AntiHBS- Tenofovir/11 20/CR 74/ IgGkappa/2 4/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/18 52/PR 45 /IgGkappa/3 4/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBs- Tenofovir/16 58/VGPR 61/ IgGkappa/3 5/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/13 45/VGPR 43/IgAlambda/3 6/+/+ HBsAg-,HBeAg-AntiHBeAg+,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/7 58/PD 67/ IgGkappa/3 5/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/12 66/PD Disclosures No relevant conflicts of interest to declare.