According to a research led by Professor Li Taisheng with Department of Infectious Diseases, PUMCH, for Efavirenz, a first-line HIV drug in China, its side-effect is related to its concentration in blood, and for Chinese patients, especially those who weigh less than 60kg, a dose 1/3 less is safer. The result was published May 15 on HIV Medicine, an internationally renowned journal on HIV research.

Efavirenz, a NNRTI recommended by WHO, has been used as one of first-line drugs in all developing countries. So far the WHO Guidelines still follow the recommended daily dose of 600mg, a decade-old standard in European and American countries. From 2005 the drug entered China’s free treatment catalogue and from 2011 was widely used as a first-line drug. Presently China has around 260,000 patients on therapies containing Efavirenz. Therefore it is of great significance to further optimize the “China Plan” for HIV by researching into Efavirenz’s individual impacts and mechanisms of after-effects on patients here.  

Since 2012, supported by a state fund for infectious diseases for the 12th Five-Year Plan (2011-2015), Professor Li, leading an HIV plus pharmacy team, was the world first to observe the relations between Efavirenz’s blood concentration and weight from a PK/PD perspective, and first revealed the reasons of greater side-effects upon 600mg dose, as well as the difference between different weights. In five years, researchers chose 455 cases from seven provinces/municipalities across China, and collected from them 1,198 plasma samples at a treatment time of four, 24, and 48 weeks. They used HPLC-UV to measure the Efavirenz concentration in blood and had multi-factor analysis. They found that, at 600mg daily dose, Chinese patients had a higher concentration than expected. For those weighing more than 60kg, 40% had a concentration higher than 4.0mg/L, the upper limit of therapeutic window (ideal content), whereas for those weighing less than 60kg, more than 50% had a concentration higher than designed. This means the daily 600mg dose is not safe for lower-weight Chinese patients. Therefore, Li suggests that patients weighing less than 60kg take 400mg daily instead of 600mg.

Compared with Nevirapine, another common drug, Efavirenz has advantages in terms of liver injury and allergic rash, but it has bigger nervous impact and causes high blood lipids, said Li. According to the research, a reduction in the daily dose of Efavirenz can not only save state money significantly but effectively reduce clinical symptoms including liver malfunction, dizziness, insomnia and high blood lipids, therefore improving patient compliance and drug efficacy. Since 2015, developed countries started a new set of first-line therapies to reduce side-effects by replacing NNRTIs with newly researched INSTIs such as Dolutegravir and Raltegravir. But they will cost nearly 2,000 yuan a month compared with 78 yuan in the case of Efavirenz.