From drugless to preventable and controllable, FDA's contribution to the fight against AIDS

On June 5, 1981, American scientists first reported clinical cases of AIDSSince the early 1980s, people from all walks of life have been working together to fight the HIV / AIDS epidemic and firmly to eliminate the diseaseIn the past 37 years, people's understanding of HIV has gradually deepened, and many important progress has been made in the development of therapeutic drugs and diagnostic testsAt the end of September this year, Drned Sharpless, former acting director of FDA, sent a message on FDA's website, detailing FDA's contribution to the fight against AIDS< br / > ▲ Drned Sharpless, former acting director of FDA (picture source: FDA website) < br / > from no drug to preventable and controllable < br / > for professionals in the field of public health, the AIDS crisis is a particularly instructive exampleLooking back on the evolution and development of coping with the AIDS crisis, the most valuable thing is that these changes are consistent with the medical training, professional development and professional experience we have experiencedIn 1990, there was a time when I worked in the HIV laboratory from medical school to the National Institutes of Health (NIH) to study what was then known as "AIDS dementia"The next internship and research in the hospital happened to be at the time when the AIDS epidemic was the most seriousAt that time, many of the most important AIDS treatment methods that we now know were not bornI've treated a lot of desperate patients and watched them die of AIDS< br / > since then, we have made a lot of progress that seemed incredible at the timeThanks to the pioneering medical research, the concerted dedication of scientists, doctors, nurses, epidemiologists, researchers, drug regulatory agencies, as well as the most important HIV carriers and patient rights groups, we have turned the prognosis of AIDS from a terminal illness to a chronic and controllable diseaseWe are trying to succeed through programs like ending the HIV epidemic: a plan for AmericaThe plan aims to provide the most affected communities with the additional expertise, technology and resources needed to respond to the HIV epidemicIn addition, we have been working through organizations such as the president's AIDS Advisory Council across the government, including the regional ending the HIV epidemic< br / > FDA has played an important role in the concept change of AIDS patients at home and abroadThroughout the FDA, all drug product review centers are committed to the important work related to HIV research and product developmentFDA experts, through the implementation of interdisciplinary review and supervision plan, help to promote the development of effective treatment drugs, and approve more and more anti AIDS drugs and fixed dose compound drugsIn addition to therapeutic drugs, FDA's work has led to more accurate diagnostic tests, successful development, reliable blood donor screening, and effective public education programsThese are all areas of sustained concern< br / > ▲ in 1988, FDA announced the interim regulatory procedures (data source: reference [2], wechat team drawing of Wuxi apptec) to accelerate the review of new therapeutic drugs for patients without drugs, and ensure the safety and efficacy of drugs, 29 antiretroviral drugs (ARV) have been approved for AIDS treatment and prevention, including multiple drug categories and multiple fixed dose compound drugs of these drugsAmong the drugs, including the first anti HIV monoclonal antibody approved by the FDA last year, is intended for use in 5000 to 10000 patients in the United States who are resistant to a variety of existing therapies< br / > until recently, for example, it was thought that three antiretroviral drugs were needed to initiate and maintain treatmentTwo years ago, the FDA approved the first dual drug therapy (Juluca) for maintenance treatment of patients with virologic inhibition; and just a few months ago, the FDA approved dovato (dolutegravir and lamivudine fixed dose compound drug), a dual drug compound treatment drug, for the treatment of patients who had previously used antiretroviral drugs, Adult patients with no known or suspected drug resistance to dovato components< br / > data source: reference [5], pharmaceutics Kant content team mapping < br / > FDA is reviewing proposals for the development of new dosage forms, such as injections and implants for HIV treatment or preventionThese dosage forms can extend the effectiveness of the dosage to 1 week, 1 month, or even longer, making the patients more convenient, better compliance and better effectThe industry is also developing microbicides to prevent the spread of HIV through the vagina and rectumBut no matter which program is adopted, we can be sure that these products will not work unless the patients take them on time and according to the regulations< br / > FDA has been at the forefront of AIDS preventionIn 2012, the FDA approved the pre exposure prophylactic drug (PREP) truvada for adults who are not infected with HIV but have a high risk of infectionThe FDA initially approved the drug for use in adults, and the indications have since expanded to include adolescents aged 15 to 17 On July 1, 2019, FDA released truvada's risk evaluation and mitigation strategy (REMS) Although FDA has determined that truvada still has safety risks, REMS requirements are no longer necessary to ensure that the benefits of the drug outweigh the risks REMs assessment shows that formulators and consumers are aware of the potential risks associated with truvada's daily use and that the Centers for Disease Control and Prevention (CDC), state and local health departments and other public health institutions can provide educational materials and treatment guidelines at any time < br / > balancing support for innovation and competition is an important focus of FDA FDA has been focusing on increasing the production of new drugs and affordable drugs, especially the generic drugs of important and some historical drugs that many patients depend on for survival In this work, the FDA Office of generic drugs (OGD) plays a key role in reducing costs and improving the accessibility of antiretroviral drugs OGD does this by reviewing the simplified new drug application (anda) and providing other support for application submission < br / > another focus of FDA concerns pediatric patients Less than half of the world's 2.1 million children living with HIV have been treated with anti HIV drugs In March 2019, the FDA released the final version of the industry guide, which provides overall recommendations for the development of antiretroviral drugs for the treatment of children with HIV The purpose of FDA is to help the sponsor understand when it is appropriate to start pediatric preparation development and pediatric research < br / > picture source: reference [8] < br / > prevention first: developing vaccines to protect individuals from HIV infection < br / > developing vaccines to protect people from HIV infection is a key area of HIV protection scientific research The complexity of the interaction between HIV and human immune system requires new methods to design HIV vaccine and vaccination programs, including some methods combining long-term use of different vaccine candidates < br / > the main work of the FDA Center for biological evaluation and Research (CBER) involves supporting safe and effective vaccine development by promoting and promoting scientific innovation For CBER, it is essential to provide an effective scientific and vaccine regulatory assessment capability CBER provides a unique perspective for FDA by conducting research activities in combination with its regulatory activities, and promotes the interaction between regulatory agencies and vaccine developers The review of CBERS has played a crucial role in evaluating rapidly developing technical and scientific issues related to the safety, efficacy and effectiveness of vaccines, including potential HIV vaccines FDA will continue to play an important role in determining vaccine evaluation strategies that provide preliminary evidence of effectiveness < br / > over the years, CBER has been consulting with external expert advisory committees and multiple stakeholders on HIV vaccines These consultations involve a range of issues related to clinical trial design and end points, as well as pre clinical testing strategies for HIV vaccines produced for new cell types A number of HIV vaccines have entered clinical trials CBER evaluates vaccines at all stages of clinical development, so that the scientific community and the industry can work together to develop detection strategies and determine the appropriate end point of HIV vaccine research In this regard, FDA plays an indispensable role For example, the FDA has developed a diagnostic program called HIV selectest that can detect HIV through infection in individuals participating in HIV vaccine trials < br / > let the public get testing < br / > through voluntary and routine testing, so that patients can know whether they are infected with HIV, is one of the most critical steps to combat the HIV epidemic According to the data released by the CDC, more than one million people in the United States are infected with HIV, of which about 15% of the infected do not know that they are infected with HIV Although HIV testing is very accurate, there is no test that can detect the virus immediately after infection < br / > data source: reference [7] team drawing of Wuxi apptec content < br / > main detection methods are shown in the figure below: < br / > data source: reference [7], team drawing of Wuxi apptec content < br / > most HIV tests, including the fastest test and home test, are anti physical examination tests, and infection can only be detected after the human body produces enough antibodies, This process takes about three to 12 weeks There was a time interval of 2 to 6 weeks between infection and detection Although there is a fast combination test approved by FDA, it is still recommended to use these methods in laboratory test A nucleic acid test used to detect HIV DNA or RNA, with a window period as short as one week after infection < br / > currently, HIV diagnosis enters the U.S market through the premarket approval (PMA) At present, there are 1 FDA approved home HIV test, 8 FDA approved care point diagnostic reagents, 12 FDA approved laboratory diagnostic reagents, and 6 supplementary tests to confirm the screening results < br / > FDA is considering reclassifying HIV diagnosis, supplementation and viral load monitoring tests from category III (PMA submission) to category II (510 (k) channel) If there is enough information to establish special controls other than general controls to reasonably ensure the safety and effectiveness of these tests, then the burden of entering the market through channel 510 (k) is less, which can shorten the pre market review time, more timely return visit, and reasonably ensure the safety and effectiveness of these tests < br / > the existing antibody detection cannot distinguish the antibody from the infant and the mother; therefore, there is no nucleic acid detection available for early diagnosis of infants Therefore, the FDA also focuses on two other areas that need more diagnostic development: tests that can distinguish between HIV-1 and HIV-2 antibodies, and tests that diagnose HIV infection in infants born to HIV positive mothers These are important steps in developing a rigorous and reliable diagnostic procedure and part of advancing patient care < br / > the role of blood screening in HIV prevention < br / > FDA plays an important role in ensuring the safety of national blood supply by minimizing the risk of HIV transmission through blood transfusion In the United States, all blood and blood component donors are reviewed for past medical history