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A monthly vaginal ring that slowly releases an antiretroviral drug (ARV) called dapivirine is undergoing regulatory review. If approved, the dapivirine ring would be the first method of biomedical HIV prevention developed specifically for women. It is important to note that this would also offer women another option than oral PrEP, which involves the daily use of a tablet called Truvada. Oral PrEP is already approved and is being rolled out in many countries.
However, the problem with these prevention methods that may contain ARVs is that their use by someone already unknowingly infected could allow the virus to become resistant to ARVs and other drugs of the same class, as ARVs may be enough. . to prevent HIV, it is not enough to prevent the virus from continuing to replicate in an infected person. In addition, if this person were to infect the drug resistance virus with others, it would be increasingly difficult to control HIV with essential drugs.
The new findings presented today at the Biennial Research Conference on HIV Prevention (HIVR4P 2018) suggest that the risk of developing drug resistance with the use of the ring Dapivirine is minimal, although researchers warn that their results represent only one study.
Researchers from the Microbicide Trial Network (MTN), funded by the National Institutes of Health, analyzed plasma samples of HIV-positive women during the ASPIRE Phase III trial using both a standard genotyping and a new generation more sensitive sequencing technique. Both tests identify changes, or mutations, in the genetic makeup of HIV that are known to cause resistance to certain drugs. Next-generation sequencing, which is only used in research, can target a specific region of a gene and detect mutations rarely seen with standard assays.
Among HIV-infected women with ASPIRE, relatively few had evidence of resistant virus, particularly drug-resistant viruses of the same class as dapivirine, called non-nucleoside reverse transcriptase inhibitors (NNRTIs). In addition, the researchers found no rare mutation associated with resistance.
The results suggest that the rare cases of resistance to NNRTIs were probably due to women infected with a drug-resistant virus and not to the use of the dapivirine ring at the time of infection.
"We have been very careful using the most sensitive tests capable of detecting the genetic changes of thousands of individual viruses in a single infected person," said Urvi Parikh, Ph.D., associate director of Virology's Virology Laboratory Center. Trials Network (MTN). and pharmacodynamics at the University of Pittsburgh. "In this study, we found that the risk of dapivirine-related resistance in a person using the dapivirine ring was the same as that of a person who did not use the ring. . "
ASPIRE, which was led by MTN, recruited 2,629 HIV-negative women aged 18-45 from 15 trial sites in Malawi, Uganda, South Africa, and Zimbabwe. The dapivirine ring, to be used for one month at a time, was developed by the International Nonprofit Partnership for Microbicide Control (IPM). The IPM has also led The Ring Study, a phase III sister monthly ring study with similar safety and efficacy results, and is seeking approval. regulatory of the ring.
Of the 2629 women who participated in ASPIRE, 168 became infected with HIV. Plasma samples from 165 women were subjected to standard genotyping drug resistance tests (96 samples of women assigned to use the placebo ring and 68 samples of females from the dapivirine ring group), while 123 samples were taken. were also analyzed using the most sensitive (61 in the placebo group and 62 in the dapivirine cycle group).
Standard genotyping showed no difference in the frequency and patterns of HIV drug resistance between those assigned to use the monthly ring of dapivirine and those assigned to those using a placebo ring, with 8 out of 69 (11.6 %) of the group having a cycle of 10.4%) of the placebo group having a resistant virus.
Resistance to dapivirine is most often associated with the presence of one of four specific mutations. Both tests yielded the same results, revealing only two cases of NNRTI resistance in women of the daphnidic dapivirine group who contracted HIV, each involving the same mutation (K103N).
In examining other mutations common in NNRTIs, the sensitive test revealed only one case not detected by the standard test. Finally, when the researchers limited their search to the specific region of the gene where NNRTI mutations were most likely to exist, they found no significant differences in the type or frequency of mutations between cyclic groups. placebo and dapivirine.
"Dapivirine remains mainly in the vagina, where it is needed to protect against HIV infection, very little drug gets into the bloodstream and goes elsewhere in the body, but if HIV had to cross the barrier anti-drug in the vagina and start to multiply in the blood, there probably not enough circulating dapivirine to be noticed and make emerge a resistant virus, "explained Dr. Parikh.
Truvada, which contains the antiretroviral drugs emtricitabine and tenofovir, is used for both HIV prevention and, in combination with other drugs, also for the treatment of HIV. Dapivirine, on the other hand, has been developed exclusively for the prevention of HIV, although other drugs in its NNRTI class are used for treatment. Women who contracted HIV during ASPIRE immediately stopped using the ring assigned to them in order to prevent the virus from becoming resistant to dapivirine or d & # 39; Other NNRTIs, such as efavirenz and nevirapine, which are commonly used to treat HIV. Similarly, with PrEP, a person must get a negative HIV test before starting the schema and be tested regularly thereafter.
IPM holds an exclusive worldwide license for dapivirine from Janssen Sciences Ireland UC, one of Janssen's Janssen Pharmaceuticals, designed to ensure that women in resource-limited settings have affordable access to any dapivirine-based microbicide .
A total of 20 oral presentations and posters will be presented by MTN investigators at HIVR4P 2018, 22-25 October. Additional presentations include two plenary lectures and a number of satellite sessions and conference symposia.
Explore further:
The dapivirine ring did not confer drug resistance in women who became infected with HIV under ASPIRE
More information:
Dr. Parikh will discuss her summary, Sequencing of New-Generation Sensitive HIV-1 from Seroconverters of the MTN-020 / ASPIRE Study on the Dapivirine Vaginal Ring, at a press conference official on HIVR4P on Wednesday 24 October from 12:00 to 13:00. THIS.
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