Tenofovir Disoproxil Fumarate For Prevention Research Articles

Tenofovir disoproxil fumarate for prevention of mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis of randomised control trials.

Hepatitis B virus (HBV) infection caused by mother-to-child transmission (MTCT) continues to pose challenges to global health. This study aimed to assess the efficacy and safety of tenofovir disoproxil fumarate (TDF) for preventing HBV MTCT. PubMed and the Cochrane Central Register of Controlled Trials were searched through August 2020. Randomised controlled trials (RCTs) were selected that evaluated the efficacy and safety of TDF for preventing MTCT of HBV compared with the standard of care, placebo or other HBV therapies. The primary outcomes were HBV MTCT rate and maternal HBV DNA level. Secondary outcomes were infant and maternal safety outcomes. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, and prospectively registered on PROSPERO (CRD42020186275). Of 240 citations, three RCTs that involved 651 participants were included. The pooled result showed that TDF can reduce the risk of HBV MTCT after 6 months postpartum by 80% (risk ratio [RR]0.2, 95% confidence interval [CI 0.06-0.7], n=584) with low heterogeneity (I2 =0%). TDF demonstrated HBV DNA suppression at delivery, though there was heterogeneity among individual studies (RR0.13, 95% CI [0.08-0.20] and (RR0.36, 95% CI [0.27-0.49]). Maternal and infant safety outcomes were comparable among treated and untreated mothers and infants born to them. The quality of evidence varied from high to very low. There is evidence that TDF effectively interrupted MTCT of HBV and suppressed HBV DNA level. Available studies on safety are very limited and heterogeneous, emphasising the need for additional RCTs with complete safety indicators.

24: Use of tenofovir disoproxil fumarate for prevention of perinatal transmission of hepatitis B virus (HBV) infection in highly viremic pregnant women: a case series

In women with high HBV DNA levels, the use of antenatal anti-viral medication in addition to hepatitis B vaccination and immunoglobulin (HBIG) for the neonate has been shown to further reduce the vertical transmission rate. The purpose of this study was to examine the efficacy of tenofovir prophylaxis to reduce maternal HBV DNA levels and vertical transmission in highly viremic women.

Tenofovir Disoproxil Fumarate for Prevention of Vertical Transmission of Hepatitis B Virus Infection by Highly Viremic Pregnant Women: A Case Series

Despite appropriate immunoprophylaxis, up to 10 % of infants born to highly viremic hepatitis B virus (HBV-DNA ≥ 7 log IU/mL) mothers are infected with HBV. Use of TDF to prevent vertical transmission (VT) by such mothers has not been evaluated. To evaluate the efficacy and safety of TDF in preventing VT from highly viremic HBV-infected mothers. Data were collected retrospectively from HBV mono-infected, hepatitis B e antigen (HBeAg) positive, pregnant women between 6/2008 and 11/2010. Cases enrolled were HBV mono-infected mothers who received TDF (300 mg orally once a day) in the third trimester. Those with pregnancy complications or an abnormal fetus on sonography were excluded from use of TDF. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. Eleven Asian mothers received TDF at the median gestational age of 29 (28-32) weeks and the median duration of TDF use before delivery was 10 (7-12) weeks. A significant reduction in serum HBV-DNA was achieved at delivery compared with baseline (mean 5.25 ± 1.79 vs. 8.87 ± 0.45 log(10) copies/mL, respectively; p < 0.01). Three had serum ALT levels more than 1.5 times the upper limit of normal and two of these normalized before delivery. The 11 infants were born with no obstetric complication or birth defects. Five infants were breastfed. All infants were hepatitis B surface antigen negative 28-36 weeks after birth. Our preliminary data suggest that TDF use in the third trimester is safe, and effectively prevents VT of HBV from high viremic HBeAg-positive mothers.

Intravaginal ring delivery of tenofovir disoproxil fumarate for prevention of HIV and herpes simplex virus infection

A safe and effective topical prevention strategy will likely require sustained delivery of potent antiviral drugs and a delivery system that simultaneously maximizes drug distribution and overcomes the behavioural challenges related to adherence. Activity against HIV and herpes simplex virus (HSV) would be advantageous, given the epidemiological link between the two pathogens. We hypothesize that tenofovir disoproxil fumarate (tenofovir DF), a prodrug of tenofovir, may be more potent than tenofovir and ideal for sustained intravaginal ring (IVR) delivery. The anti-HIV and anti-HSV activity of tenofovir and tenofovir DF were assessed in cell and explant models. Cumulative tenofovir DF release and stability from polyether urethane (PEU), ethylene-co-vinyl acetate (EVA) and silicone IVRs were compared, and the activity and safety of drug released were evaluated in cervical explants and in a polarized dual-chamber model. Tenofovir DF inhibited HIV and HSV at ≈ 100-fold lower concentrations than tenofovir and retained activity in the presence of semen. PEU rings delivered >1 mg/day of tenofovir DF for 30 days. Pre-treatment of cervical explants with 10 μg/mL tenofovir DF or eluants from PEU minirings resulted in >90% inhibition of HIV and reduced HSV-2 yields by 2.5 log. Tenofovir DF and eluants did not prevent cell growth or polarization, or have any deleterious effects on an epithelial barrier. The findings support the development of a PEU tenofovir DF ring, which may provide potent and sustained protection against HIV and HSV.

Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial

Objectives:The objective of this trial was to investigate the safety and preliminary effectiveness of a daily dose of 300 mg of tenofovir disoproxil fumarate (TDF) versus placebo in preventing HIV infection in women.Design:This was a phase 2, randomized, double-blind, placebo-controlled trial.Setting:The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.Participants:We enrolled 936 HIV-negative women at high risk of HIV infection into this study.Intervention:Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.Outcome measures:The primary safety endpoints were grade 2 or higher serum creatinine elevations (>2.0 mg/dl) for renal function, grade 3 or 4 aspartate aminotransferase or alanine aminotransferase elevations (>170 U/l) for hepatic function, and grade 3 or 4 phosphorus abnormalities (<1.5 mg/dl). The effectiveness endpoint was infection with HIV-1 or HIV-2.Results:Study participants contributed 428 person-years of laboratory testing to the primary safety analysis. No significant differences emerged between treatment groups in clinical or laboratory safety outcomes. Study participants contributed 476 person-years of HIV testing to the primary effectiveness analysis, during which time eight seroconversions occurred. Two were diagnosed in participants randomized to TDF (0.86 per 100 person-years) and six in participants receiving placebo (2.48 per 100 person-years), yielding a rate ratio of 0.35 (95% confidence interval = 0.03–1.93), which did not achieve statistical significance. Owing to premature closures of the Cameroon and Nigeria study sites, the planned person-years of follow-up and study power could not be achieved.Conclusion:Daily oral use of TDF in HIV-uninfected women was not associated with increased clinical or laboratory adverse events. Effectiveness could not be conclusively evaluated because of the small number of HIV infections observed during the study.