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

Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated.. The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection.. Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series.. PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.

Topics: Adult; Anti-HIV Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Hepatitis B, Chronic; HIV Infections; Homosexuality, Male; Humans; Liver Function Tests; Male; Middle Aged; Pre-Exposure Prophylaxis; Transgender Persons; Young Adult

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