PrEP in the future
Last month's announcement that the Bill and Melinda Gates Foundation will give up to $ 140 million for a drug device manufacturer in Boston to develop an implantable subdermal device minipump to provide medicines for pre-exposure prophylaxis (PrEP) against infection HIV, which has focused attention on the future of PrEP. It would be the future of PrEP totally focused on implants or was this one of the many and varied options for people who want to use PrEP?
Implants and other long-acting drugs in the delivery systems have attracted interest as a means of providing PrEP because studies consistently show that non-adherence - missing doses or do not use an intravaginal ring - is strongly correlated with the lack PrEP protection. On the other hand, studies also show that people who maintain adequate levels of PrEP drugs are protected from HIV infection.
Intarcia is a company based in Boston, implantable development of mini-pump about the size of a toothpick, also to inject a drug to control blood sugar in people with type 2. Product - ITCA Intarcia 650, which offers the drug exenatide to 2 type of diabetes - is already under review by the Food and Drug Administration of the United States, after the successful phase III trials and might turn out to be licensed at the end of 2017.
Last month Intarcia announced that it had secured a grant of US $ 50 million from the Bill and Melinda Gates Foundation to develop your mini mini gun technology to provide antiretroviral drugs for PrEP. Over $ 90 million will be donated to support access to the device in low and middle income countries and, if successful, there is the possibility of achieving a number of milestones.
The mini-pump technology is Intarcia an implant that is placed under the skin and dispense a quantity of controlled drug each day. At this point Intarcia is not authorize use of a particular antiretroviral PrEP product as a delivery system. Development tests seek to identify the drug can be delivered at levels sufficient to prevent HIV infection.
Several other research groups and companies have reported promising results of subdermal implants in animal testing, although the technology of implant Intarcia appears to be the most advanced. The Auritec, a branch company of the autonomous injection ARV injection, Pasadena, received funding from National Institutes of Health to test intravaginal rings for autonomous injection of PrEP, and has also tested an implant containing tenofovir alafenamide (TAF) in dogs. The 40 day study showed that the implant was hood to maintain plasma levels of drug concentration 30 times higher than required to protect against HIV infection throughout the study period.
The PEPFAR United States President (Emergency Plan for AIDS Relief) has alsosupported researchabout a subcutaneous implant for delivery of TAF, developed by the University of California in San Francisco, which is still at an early stage of development. A larger research project, sustained protection against long-term HIV (SLAP-HIV), a partnership based in Chicago and Northwestern UniversityHe received a financial support of $ 17 million guaranteed by the American Health Agency National Institutes of Health, Is working to develop an implant that can provide any of these drugs: cabotegravir, rilpivirine, or tenofovir TAF exalidex analogcurrently being developed for hepatitis B). Researchers also have the hope that their work will lead to the development of implants for antiretroviral therapy long-acting, eliminating the need of taking pills daily.
The development of injectable PrEP is more advanced than PrEP implants, and can provide an interim measure on the way to implants that provide protection for up to a year. It can also provide short-term protection for people who need PrEP long action, but, for whatever reason, do not want an implant. Unlike implants, that can be detectable under the skin and therefore unacceptable for some people, an injection is invisible to others and need not be removed or replaced when the active drug is dissolved.
The disadvantage of injectable PrEP - and perhaps breast implants - is that the long-acting formulations were able to prolong the levels of antiretroviral drugs at low levels in the body for a short period of months, exponenciar the risk of developing drug resistance to HIV infection occurs [translator's note. it has appeared, and I have material to translate and revise taking note of newly infected patients for whom first-line drugs are not functional, burning an important step in treatment, which may last for decades. I would tell people who use PrEP that do conscientiously, using it as a secondary protection factor, NOT LEAVING THE CONDOM USE]The ÉCLAIR cabotegravir study of the injectable PrEPIt was found that almost one quarter of the participants still had drug levels that would probably be able to prevent HIV infection for a period of six months after their last injection, while 41% suboptimal levels were still detectable at this point.
injectable PrEP is being tested at intervals of eight weeks by injection, requiring a high frequency of outpatient visits, which may not be suitable for all. [Editor's note: There is an article on this site that just says that the needs of constant visits to clinics are counterproductive and you can read it here (Opens in new window)]
Intramuscular injections may also be unacceptable to some, although the user satisfaction ÉCLAIR (closing) of the study was high.
The development of injectable PrEP is focused on the use of two drugs, cabotegravir and rilpivirine, which are also being developed as injectable nano long-acting formulations for treatment of HIV infection by the Viiv Healthcare.
The ViiV Healthcare is working on an injectable formulation of long-acting cabotegravir antiretroviral therapy, which recently entered into a large Phase III study in the United States, Latin America and Africa in men who have sex with men and transgender women. The study HPTN 083, sponsored by NIAID (National Institute of Allergy and Infectious Diseases),has, in its scope, 4500 people to receive one cabotegravir injection every eight weeks or takeTruvada(Tenofovir / emtricitabine) every day for an average of four and a half years. The results are expected in 2021 (healing so vaunted for 2020 been to vinegar, despite the sensational video that took this response of the scientific community). A study companion, HPTN 084, Will begin testing injectable cabotegravir in young women in sub-Saharan Africa this year. Results of a phase II safety study (HPTN 077) are expected in early 2018.
PATH is testing injectable rilpivirine in women under license from Janssen manufacturer, in a phase II safety study (HPTN 076). Taking place in the United States, South Africa and Zimbabwe. The results are expected in February 2017. Injections of rilpivirine are being given every eight weeks in this study.
vaginal rings containing dapivirine a ITRNN They have been tested in several phase III studies (ASPIRE and the RING study) And found to reduce the risk of infection 65% in consistent users inASPIRE study. The rings were less effective in younger women due to less consistent use, indicating a need for more exciting action methods or less complicated for this particular population. The dapivirine ring is likely to undergo licensing review in 2018, and future developments will include experiences with rings containing other antiretroviral agents, including TAF and maraviroc, an HIV entry inhibitor. Multipurpose rings that act as contraceptive rings and against the the HIV PrEP are also in development.
Contraception experiences highlight the value of multiple options
While the implants and injectables are likely to be attractive to many people, they do not replace the oral PrEP to those in need. Some people may want to use PrEP only for a short period of time, or may like the idea of an injection or an implant.Lessons from contraception (This article will be translated soon) show that the mixture of options is a right inherent to all and provide these options successfully, it is important and strictly necessary.
A global analysis of contraceptive funding demonstrated that broadening the range of contraceptive options increased the overall use of contraception - Every new widely available method total contraceptive users, increased use of contraceptives by 4-8% between 1982 and 2009. contraception studies suggest that a choice of method supports access and use.
Contraceptive studies in populations at risk for HIV infection show large variations in the type of contraception used from each country for each country, among the women participating in microbicide studies. For example, considering that predominated in Malawi, injectable contraception, oral contraception prevailed in Zimbabwe. These historical patterns are structured by the influence of the supplier and the health care provider over several decades and can influence the ways in which health services are beginning to offer different forms of PrEP. For example, greater experience with injectable or implantable contraception can lead to faster adoption of these modes when targeting women at higher risk of infection.
However, it is important to avoid assumptions about what kind of product is suitable for a specific population - this can act as a factor of obstacle to its further use by other groups of people. For example, targeting a particular form of PrEP for sex workers may have the unintended effect of making other women reluctant to use it for fear of being identified as a sex worker. Translator's note: This is the most obvious of views. Let us imagine that the toothpaste "I am what I am" to be released in Brazil and see how would the provisions of toothpastes in supermarkets.
It is also important to remember that without a well-organized health system (SUS are killing and this "Tramp - R S R" is threatening the "Obama Care" PrEP any method may be short commercial life). For example, if the systems are not oiled and attentive to remind people of the need to return to the clinic to receive new injections or implants, many people will no longer be protected.Translated by Claudio Souza's original Rmplants and injectables: PrEP in the future Keith Alcorn Published in Aidsmap Reviewed by Mara Macedo