Inventor of Viread/Tenofovir died today - comments from sStudyforhope

StephenW

He was an ingenious organic chemist, developed first adefovir, then, together with de Clerq in Belgium Tenofovir a compound which has only one Methyl group additional attached to Adefovir, which was surprisingly reducing its toxicity by at least 50fold.

Due to the extremely low susceptibility to resistance and very low toxicity this drug became the cornerstone of antiviral treatment for HIV and HBV. It made Gilead Billions, of which Holy has seen a million a year grant for his Institute in Prague.

At the day he died, the FDA had approved Truvada, a combo of tenofovir and emtricitabine (FTC) (300/200mg) for use as a preventative in healthy individuals exposed to risk of infection. This is at least some indication, that the toxicity analysis that the FDA had conducted has at least not shown a strong toxicity signal assoociated with its use. The trial has shown a 96% reduction in infection events compared to placebo.

The dramatic suppression of the HBV virion production/output reduces the signal of infection to the immune system, which causes in turn a reduction in the damage done to the liver by the chronic unsucsessful attack of immune activation. it reduces chronic active hepatitis into very mild or no hepatitis, leading to reduction or reversal of fibrosis and even cirrhosis ( in not too advanced cases) in the vast majority of cases.

Unfortunately,  as a side effect of the critical benefit of liver disease reduction, the turnover oof cccDNA infected cells also slows down, since the immune elimination becomes a very slow event. Eventually a very slow daily elimination is balanced by a slow but still existing reinfection spreading, an equilibrium state of fairly low level HBV presence in the liver. Thus the surface antigen, produced by the remnannt cccDNA, will not be eliminated in the majority of patients. And a low level, but long term toxicity, ill defined at the moment, will also persist.

But it is time for a moment of thoughtful gratitude to Antonin Holy, who saved countless millions.                           

StephenW

他是一个巧妙有机的化学家，开发第一阿德福韦，然后，一起在比利时泰诺福韦的化合物，其中只有一个甲基组附加阿德福韦，这是令人惊讶的减少由至少50fold的毒性Clerq。

由于阻力极低的易感性，毒性非常低，这种药物成为艾滋病毒和乙肝病毒的抗病毒治疗的基石。基列的数十亿美元，这神圣的一百万一年资助他在布拉格研究所。

在他去世的那一天，FDA已批准Truvada，替诺福韦和恩曲他滨（FTC）（300/200mg）作为预防感染的风险暴露的健康个​​人使用的组合。这是至少有一些迹象表明，至少不会表现出很强的毒性与其使用的信号assoociated，FDA已进行毒性分析。试验表明在感染事件与安慰剂相比，减少96％。

显着抑制乙肝病毒颗粒生产/输出，降低了信号的感染的免疫系统，这导致在打开一个减少慢性免疫激活unsucsessful的攻击肝脏的损害。它减少到非常轻微或没有肝炎慢性活动性肝炎，导致在绝大多数情况下，减少或纤维化，甚至肝硬化的逆转（在不太先进的情况下）。

不幸的是，作为一个副作用，减少肝病的关键利益，营业额OOF cccDNA的感染细胞也减慢，因为免疫消除成为一个非常缓慢的事件。最后一个非常缓慢的日常消除是一个缓慢的，但仍然存在再感染的蔓延，一个相当低的水平在肝脏中HBV存在的平衡状态平衡。因此，表面抗原，由remnannt cccDNA的产生，不会被淘汰，在广大患者。和一个较低的水平，但长期毒性，生病的时刻定义，也将持续下去。

但它是一个周到的感谢圣安东尼，谁拯救了无数百万时刻的时间。

咬牙硬挺

默哀，人类的重大损失！

StephenW

Renowned HIV scientist Holy dies at 75               

[Date: 2012-07-18]

                               

Antonin Holy, the prominent Czech chemist whose research helped revolutionise the development of antiviral drugs used in the treatment of HIV and hepatitis B, died on 16 July. He was 75.

The Institute of Organic Chemistry and Biochemistry at the Czech Academy of Sciences, where Dr Holy began working in 1960, said he died after battling an unspecified long-term disease.

The Czech scientist, whose work focused on nucleic acid chemistry, was instrumental in discovering substances that form drugs used to treat patients with AIDS, HIV, hepatitis B, smallpox virus and eye inflammation.

Dr Holy passed away on the day that health regulators in the United States gave a green light for Truvada, a drug that he helped develop, to be used in the treatment of patients who are at a higher risk of contracting the virus that causes AIDS. The drug, which includes the drug Viread that is used to treat retinitis in AIDS patients, is used to prevent infection. Dr Holy and virologist Erik De Clercq, a leading researcher at the Katholieke Universiteit Leuven in Belgium, developed Viread. They began working together in 1976.

Gilead Sciences Inc., a United States-based pharmaceutical company and the maker of Truvada, donated millions of dollars to the Institute of Organic Chemistry and Biochemistry, and a portion of that donation helped fund Dr Holy's work.

'It is a huge loss,' said Zdenek Havlas, a former director of the Institute of Organic Chemistry and Biochemistry at the Czech Academy of Sciences, and a colleague of Dr Holy's. 'He belonged and he always will belong among the greatest chemists and scientists. He had a special talent for looking at a chemical structure to tell immediately whether it was worth continuing to explore and whether it would have any effects.'

Dr Holy was born in Prague on 1 September 1936. For the most part, he worked alone and was banned from supervising students under the communist regime in the former Czechoslovakia. Dr Holy was given permission to build a team after the collapse of the communist regime in 1989, and he became a lecturer at Czech universities. The School of Chemistry at the University of Manchester in the United Kingdom granted him an honorary professorship in 2008.

Dr Holy received the European Union's Descartes Prize for Science and the Medal of Merit of the Czech Republic in 2001. His name was put forward by the Czech Academy of Sciences in 2008 to be nominated for the Nobel Prize in Medicine.

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