{"id":42218,"date":"2022-03-01T07:30:25","date_gmt":"2022-03-01T07:30:25","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=42218"},"modified":"2022-11-21T19:50:34","modified_gmt":"2022-11-21T19:50:34","slug":"croi-2022-long-acting-doravirine-implants-as-prep-to-prevent-vaginal-hiv-transmission-in-mouse-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/42218","title":{"rendered":"CROI 2022: Long-acting doravirine implants as PrEP to prevent vaginal HIV transmission in mouse study"},"content":{"rendered":"

\"CROIKirk Taylor, HIV i-Base<\/strong><\/p>\n

A poster at CROI 2022 reported results from a mouse study using a long-acting formulation of the NNRTI doravirine (LA-DOR) as PrEP that could be used in a removable implant. [1]<\/strong><\/p>\n

Long-acting (LA) HIV therapies have potential to increase adherence and reduce risk of drug-resistant mutations. Doravirine is an NNRTI that has an IC95<\/sub> of 8.1 ng\/mL against HIV-1 and has efficacy against NNRTI-resistant strains.<\/p>\n

Doravirine was stably released into the plasma of mice across the five-month study period consistently exceeded IC95 <\/sub>values.<\/p>\n

LA-DOR achieved good tissue distribution with plasma:tissue ratios >1.0. Doravirine concentrations were highest in GI tissues. Concentrations of doravirine (in three animals) in vaginal (mean: 206 ng\/g, range: 38.2 to 229), cervical (mean: 271.2 ng\/g, range: 42.5 to 336) and uterine (mean: 122.3 ng\/ml, range: 51.6 to 157) tissues displayed a wide range but were consistently above IC95<\/sub> levels at week 5.<\/p>\n

The animals were challenged by vaginal transmission. LA-DOR reduced viral load in plasma and cervical tissue sections of mice who became HIV positive by 2 and 3-5 log copies\/mL, respectively.<\/p>\n

Efficacy of LA-DOR as PrEP was assessed following repeated exposure to HIV. Detection of HIV occurred after the first exposure in 80% of mice that received placebo (n=5). LA-DOR effectively reduced vaginal HIV transmission with a single mouse testing positive after the third exposure (n=8).<\/p>\n

This preclinical study indicates that LA-DOR implants stably release drug for >5 months. Plasma (week 20) and tissue concentrations (week 5) exceeded the IC95<\/sub> and implant removal rapidly lowered plasma DOR.<\/p>\n

Further studies will evaluate the tissue distribution of DOR at later timepoints. Vaginal transmission data raise the prospect that LA-DOR implants could contribute to PrEP strategies for high-risk women.<\/p>\n

comment<\/h3>\n

NNRTIs are not generally a good class for PrEP due to the class potential for hypersensitivity reactions and low threshold to drug resistance.<\/strong><\/p>\n

The clinical implications of drug resistance are also more serious when the same drugs are commonly used for both PrEP and treatment.<\/strong><\/p>\n

Whilst the data presented are promising, the barrier for PrEP efficacy also needs to be closer to 100%, although sample sizes in this study are very small and longer-term efficacy data are required.<\/strong><\/p>\n

References<\/p>\n

    \n
  1. Kovarova et al. Long acting doravirine for treatment and prevention of vaginal HIV transmission. CROI 2022. 12-16 February 2022, virtual. Poster abstract 446.
    \nhttps:\/\/www.croiconference.org\/abstract\/long-acting-doravirine-for-treatment-and-prevention-of-vaginal-hiv-transmission\/<\/a><\/li>\n<\/ol>\n

    This report was first published on 17 February 2022.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    Kirk Taylor, HIV i-Base A poster at CROI 2022 reported results from a mouse study using a long-acting formulation of the NNRTI doravirine (LA-DOR) as PrEP that could be used in a removable implant. [1] Long-acting (LA) HIV therapies have …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,10],"tags":[],"class_list":["post-42218","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-transmission-and-prevention"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42218","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=42218"}],"version-history":[{"count":2,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42218\/revisions"}],"predecessor-version":[{"id":44396,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/42218\/revisions\/44396"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=42218"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=42218"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=42218"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}