emtricitabine--tenofovir-disoproxil-fumarate-drug-combination and Hepatitis-B

At Bristol-Myers (BM) (1985-1990), John C. Martin started his HIV career with directing the clinical development of didanosine (ddI) and stavudine (d4T). During this period, he became aware of the acyclic nucleoside phosphonates (ANPs), such as (

Topics: Alanine; Anti-HIV Agents; Drug Therapy, Combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hepatitis B; History, 20th Century; History, 21st Century; HIV; HIV Infections; Humans; Pre-Exposure Prophylaxis; Reverse Transcriptase Inhibitors; Tenofovir

According to the Americans with Disabilities Act (1990), couples with blood-borne viruses that lead to infectious disease cannot be denied fertility treatment as long as the direct threat to the health and safety of others can be reduced or eliminated by a modification of policies or procedures. Three types of infectious patients are commonly discussed in the context of fertility treatment: those with human immunodeficiency virus (HIV), hepatitis C or hepatitis B. Seventy-five per cent of hepatitis C or HIV positive men and women are in their reproductive years, and these couples look to assisted reproductive techniques for risk reduction in conceiving a pregnancy. In many cases, only one partner is infected. Legal and ethical questions about treatment of infectious patients aside, the question most asked by clinical embryologists and andrologists is: "What are the laboratory protocols for working with gametes and embryos from patients with infectious disease?" The serostatus of each patient is the key that informs appropriate treatments. This guidance document describes protocols for handling gametes from seroconcordant and serodiscordant couples with infectious disease. With minor modifications, infectious patients with stable disease status and undetectable or low viral load can be accommodated in the IVF laboratory.

Topics: Cryopreservation; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Fertilization in Vitro; Germ Cells; Hemorrhagic Fever, Ebola; Hepatitis B; Hepatitis C; HIV Infections; HIV Seropositivity; Humans; Infectious Disease Transmission, Vertical; Male; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Reproductive Techniques, Assisted; Risk; Risk Reduction Behavior; Semen; Spermatozoa; Viral Load; Zika Virus Infection

My collaboration with Prof. Antonín Holý, that spans a period of 3-4 decades (1976-2012), led to the discovery of several acyclic nucleoside phosphonates (ANPs) which were clinically developed by Gilead Sciences: cidofovir, adefovir, and tenofovir. The latter was further converted to two orally bioavailable prodrug forms, TDF and TAF, and both TDF and TAF were further combined with other antiviral drugs, thus giving rise to a broad array of antiviral drug combinations for the treatment of HIV infections. TDF and TAF are both available for the treatment of hepatitis B virus (HBV) infections, and, in combination with emtricitabine, also applicable as Truvada

Topics: Anniversaries and Special Events; Anti-HIV Agents; Antiviral Agents; Cidofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hepatitis B; Hepatitis B virus; HIV Infections; Humans; Nucleosides; Organophosphonates; Prodrugs; Tenofovir

The FEM-PrEP trial was a pre-exposure prophylaxis clinical trial to test the safety and efficacy of Truvada (tenofovir disoproxil fumarate and emtricitabine) in the prevention of human immunodeficiency virus infection. Because Truvada can suppress hepatitis B virus replication, and withdrawal of Truvada can cause hepatic flares in patients with chronic hepatitis B, pre-enrollment screening included serological screening for hepatitis B virus markers. Women with chronic infections were not enrolled in the trial. Women found to be unprotected against hepatitis B were enrolled and offered three doses of hepatitis B vaccine. Reinfection and reactivation of previously resolved hepatitis B virus infections have been documented in immunosuppressed individuals but not in healthy individuals. We present the case of a participant enrolled in the FEM-PrEP clinical trial with baseline evidence of immunity against hepatitis B virus who subsequently developed acute hepatitis B.. A 21-year-old Black non-pregnant woman was enrolled in the FEM-PrEP trial. She was human immunodeficiency virus-negative and a serological test for hepatitis B virus was negative. She had evidence of low levels of protection against hepatitis B virus and normal liver function. She had no hepatitis B vaccination history, thus it was concluded that she had post-infection immunity. At week 36 she presented with severely elevated liver enzyme levels that, upon further investigation, were a result of acute hepatitis B virus infection. The infection followed an asymptomatic course until full recovery of her liver enzymes a few weeks later. At study unblinding, the participant was found to be on the Truvada arm. Retrospective plasma drug level testing found low levels of study drugs from week 4. The participant remained human immunodeficiency virus-negative throughout the study.. Hepatitis B virus infection reactivation or reinfection is a rare phenomenon in healthy individuals. However, reactivations have been reported in patients being treated for chronic hepatitis B with the drugs contained in Truvada, after treatment had been withdrawn. This participant may have reactivated after stopping Truvada, or she may have reactivated spontaneously owing to relatively low levels of protective antibodies against hepatitis B. Alternatively, she may have been reinfected. Clinicians should be aware that hepatitis B virus reactivation or reinfection may cause elevated transaminases even in the presence of low baseline immunity.

Topics: Adult; Alanine Transaminase; Anti-HIV Agents; Clinical Trials as Topic; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Hepatitis B; Hepatitis B Antibodies; Hepatitis B virus; Hepatitis B, Chronic; HIV Infections; Humans; Liver; Practice Guidelines as Topic; Pre-Exposure Prophylaxis; Retrospective Studies; Treatment Outcome; Virus Activation

Topics: Adult; AIDS Serodiagnosis; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Health Personnel; Hepatitis B; Hepatitis C; Humans; Male; Needlestick Injuries; Raltegravir Potassium