Solomon Marc M, Schechter Mauro, Liu Albert Y, McMahan Vanessa M, Guanira Juan V, Hance Robert J, Chariyalertsak Suwat, Mayer Kenneth H, Grant Robert M
*Gladstone Institutes, San Francisco, CA; †University of California, San Francisco, San Francisco, CA; ‡Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; §Bridge HIV, San Francisco Department of Public Health, San Francisco, CA; ‖Investigaciones Medicas en Salud, Lima, Peru; ¶Research Institute for Health Sciences and Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; and #Fenway Institute, Fenway Health, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA.
J Acquir Immune Defic Syndr. 2016 Mar 1;71(3):281-6. doi: 10.1097/QAI.0000000000000857.
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.
每日口服恩曲他滨和替诺福韦酯（FTC/TDF）进行暴露前预防（PrEP）可预防HIV感染。对乙型肝炎病毒（HBV）感染情况下HIV PrEP的安全性和可行性进行了评估。
暴露前预防倡议研究将2499名HIV阴性的男男性行为者和变性女性随机分为每日口服FTC/TDF组和安慰剂组。在筛查时和停止PrEP时获取肝炎血清学和转氨酶数据。通过聚合酶链反应评估HBV DNA，并通过群体测序评估耐药性。为易感染HBV的个体提供疫苗接种。
在2499名参与者中，12人（0.5%；包括6名随机分配到FTC/TDF组的参与者）患有慢性HBV感染。在停止FTC/TDF后，活性药物组的6名参与者中有5人在随访时进行了肝功能检查。除1名参与者在停止用药第12周时肝功能检查出现1级升高（丙氨酸转氨酶=90，天冬氨酸转氨酶=61）外，停止用药后的随访中肝功能检查仍在正常范围内。没有肝损伤发作的证据。对储存样本进行的聚合酶链反应显示，活性药物组有2名参与者在入组时有急性HBV感染的证据。两人均有4级转氨酶升高的证据，随后恢复正常。总体而言，在所检测的基因型中没有TDF或FTC耐药的证据。在1633名符合疫苗接种条件的参与者中，1587人（97.2%）接受了至少1剂疫苗；1383人（84.7%）完成了全程接种。
如果没有肝硬化或转氨酶大幅升高的证据，PrEP可安全地提供给HBV感染个体。尽管有使用HBV疫苗的建议，但全球筛查时的疫苗接种率较低，不过提供疫苗接种后的接受率和效果较高。
