PrEP in the future
Last month's announcement that the Bill and Melinda Gates Foundation will give up to $ 140 million to a drug maker in Boston to develop an implantable minipump subdermal device to provide pre-exposure prophylaxis (PrEP) drugs against infection by HIV, which has focused attention on the future of PrEP. Is the future of PrEP fully focused on implants or would this be 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 from subdermal implants in animal testing, although Intarcia's implant technology appears to be the most advanced. Auritec, a Pasadena ARV injection company, has received funding from the National Institutes of Health to test intravaginal rings for self-injection of PrEP, and has also tested an implant containing tenofovir alafenamide (TAF) in dogs. The 40 study days demonstrated that the implant was designed to maintain 30 plasma levels of drug times greater than those required to protect against HIV infection throughout the study period.
PEPFAR of the President of the United States (Emergency Plan for AIDS Relief) also has supported research regarding a subcutaneous implant for delivery of TAF, developed by the University of California at San Francisco, which is still at an early stage of development. A larger research project, sustained long-term HIV protection (SLAP-HIV), a partnership based at Chicago Northwestern University and He 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, TAF or tenofovir exalidex analog currently 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 for breast implants - is that long-acting formulations were able to prolong ARV drug levels at low levels in the body for a short period of months, expose the risk of developing drug resistance if the HIV infection occurs. [Note from the translator: It has already appeared, and I have materials to translate and review giving note of newly infected patients for whom the first line drugs are not functional, burning an important step of the treatment, which can last for decades. I would tell people who use PrEP to do it consciously, using it as a secondary protection factor, NOT ABANDONING THE USE OF CONDOMS] The ÉCLAIR cabotegravir study of the injectable PrEP It found that nearly a quarter of participants still had levels of drugs that would probably be able to prevent HIV infection for a period of six months after their last injection, while 41% still had detectable sub-optimal levels 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.
ViiV Healthcare is working on an injectable long-acting cabotegravir antiretroviral therapy formulation that recently entered a major phase III study in the United States, Latin America and Africa in men who have sex with men and trans women. The study HPTN 083, sponsored by NIAID (National Institute of Allergy and Infectious Diseases), has 4500 in its scope to receive a cabotegravir injection every eight weeks or to take Truvada (tenofovir / emtricitabine) every day for an average of four and a half years. The results are expected in 2021 (the cure so vindicated for 2020 was already for the vinegar, despite the sensationalist video that led 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 by 65% in users consistent ASPIRE 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
Although implants and injectables are likely to be attractive to many people, they do not replace oral PrEP for those who need it. Some people may want to use PrEP only for a short time, or they may like the idea of an injection or an implant. Lessons from contraception (this article will be translated soon) show that the mix of options represents an inherent right at all and provide these options successfully, it is important and rigorously necessary.
An overall analysis of contraceptive uptake has shown that widening the range of contraceptive options has increased total contraceptive use - With each new method widely available, total contraceptive users have increased contraceptive use by 4-8% between 1982 and 2009. Contraceptive 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 Cláudio Souza from the original Implants and injectables: PrEP in the future
Published in Aidsmap
Reviewed by Mara Macedo