{"id":49057,"date":"2024-10-09T17:04:58","date_gmt":"2024-10-09T17:04:58","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=49057"},"modified":"2024-10-17T13:29:00","modified_gmt":"2024-10-17T13:29:00","slug":"impact-on-cd4-counts-of-once-monthly-islatravir-in-prep-studies-early-macaque-results-with-mk-8527-follow-on-compound","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/49057","title":{"rendered":"Impact on CD4 counts of once-monthly islatravir in PrEP studies: early macaque results with MK-8527 follow-on compound"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

Two oral abstracts at R4P 2024 included safety results from phase 3 PrEP studies of once-monthly oral islatravir (ISL) which were stopped early due to the potential adverse effect of reducing CD4 lymphocytes. [1, 2]<\/strong><\/p>\n

A poster at the conference included efficacy data on MK-8527, a similar compound with the potential for once-weekly oral PrEP. [3]<\/p>\n

Both phase 3 PrEP studies were randomised placebo-controlled studies comparing once-monthly oral islatravir (60 mg QM) to daily oral TDF\/FTC. Both were stopped after less than one year with all participants offered open-label oral TDF\/FTC for continued safety follow-up.<\/p>\n

No participants in either study became HIV positive during the randomised phase although incident infections were reported during the later follow-up phase.<\/p>\n

The results of the IMPOWER-22 study in cisgender women were presented by Sinead Delany-Moretlwe from the University of the Witwatersrand, Johannesburg. [1]<\/p>\n

Of the 727 cisgender women initially randomised (1:1) and treated, 95% continued in the open label study. Most participants were Black or African American (92.4%) and median age was 25 (range 18 to 46) years.<\/p>\n

During the blinded phase adverse events were reported by 55% vs 70% in the ISL vs TDF\/FTC control groups respectively, but with <2% rated grade 3 or 4.<\/p>\n

Headache was most common with ISL (11.6%), with bacterial vaginosis (15.3%), headache (14.5%) and nausea (11.2%) reported in the FTC\/TDF group. Other infections were reported in 22.4% vs 40.5% respectively.<\/p>\n

The mean total lymphocyte percentage drop at month 3 was \u201320.8% (95%CI: \u201324.0 to \u201317.6 vs \u20138.9% (\u201311.6 to \u20136.2; n=280) respectively. After one year on open-label TDF\/FTC the study only reported a trend to recovery with reductions compared to baseline of \u20136.3% (\u20138.7 to \u20133.9) vs \u20135.3% (\u20138.0 to \u20132.7), respectively.<\/p>\n

Similar results from the IMPOWER-24 study in 494 gay men and transgender women (4.5%) (randomised 2:1) were presented by Raphael Landowitz from UCLA, Los Angeles. [2]<\/p>\n

Demographics included 42% white, 25% Black\/African American, 20% Asian and median age was 27 (range 18 to 76) years.<\/p>\n

Adverse events were reported by 64% vs 77% of the ISL vs control group respectively and were mild or moderate in 96% cases. Infection AEs were reported in 37% vs 50.0% with COVID-19 being the most common (11% vs 13%, respectively).<\/p>\n

At month 3, mean percent change in total lymphocyte count was \u20137.4% (95%CI: \u201310.6 to \u20134.1) vs \u20132.7% (\u20136.9 to +1.4). At month 9 this was \u201317.4% (\u201323.4 to \u201311.4) vs 0.4% (\u20136.1 to +6.9).<\/p>\n

Although islatravir is no longer being developed as PrEP, a second NRTTI from MSD called MK-8527 is now being studied, with early results from a once-weekly macaque study presented as a poster. [3]<\/p>\n

This study included 24 animals in two active arms using different doses and one placebo arm (n=8 in each), including washout periods between dose reductions (6.0>1.0>0 mg\/kg in group 1 and 2.0>0.3>0.1 mg\/k in group 2) with 10 rectal challenges.<\/p>\n

comment<\/h2>\n

These data confirm the safety concerns and support the importance of reducing the dose in treatment studies.<\/strong><\/p>\n

The early data on MK-8527 are also very promising.<\/strong><\/p>\n

References<\/p>\n

    \n
  1. Delany-Moretlwe S et al for the IMPOWER-22 Study Group. Safety and tolerability of oral islatravir (ISL) once-monthly (QM) as pre-exposure prophylaxis (PrEP) in cisgender women at elevated risk for acquiring HIV-1. 5th R4P 2024, 6\u201310 October 2024. Oral abstract 0201.
    \nhttps:\/\/programme2024.hivr4p.org\/Abstract\/Abstract\/?abstractid=248<\/span><\/a><\/li>\n
  2. Landovitz RJ et al. Safety and tolerability of oral islatravir (ISL) once-monthly (QM) as pre-exposure prophylaxis (PrEP) in cisgender men and transgender women at elevated risk for acquiring HIV-1. 5th R4P 2024, 6\u201310 October 2024. Oral abstract 02.
    \n    https:\/\/programme2024.hivr4p.org\/Abstract\/Abstract\/?abstractid=250<\/span><\/a><\/li>\n
  3. Diamond TL et al. Weekly oral phrophylaxis with MK-8527 protects rhesus macaques from rectal challenge with SIV. 5th R4P 2024, 6\u201310 October 2024. Poster TUPE020.
    \n    https:\/\/bit.ly\/3AMI7Qm<\/a> (poster)
    \n<\/span>    https:\/\/hivr4p2024.iasociety.org\/cmVirtualPortal\/_iasociety\/hivr4p2024\/eposters#\/PosterDetail\/2207<\/a> (ePoster)<\/span><\/li>\n<\/ol>\n

    \n<\/p>","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Two oral abstracts at R4P 2024 included safety results from phase 3 PrEP studies of once-monthly oral islatravir (ISL) which were stopped early due to the potential adverse effect of reducing CD4 lymphocytes. [1, 2] A …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,10],"tags":[336],"class_list":["post-49057","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-transmission-and-prevention","tag-r4p-2024-lima"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/49057","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=49057"}],"version-history":[{"count":22,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/49057\/revisions"}],"predecessor-version":[{"id":49138,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/49057\/revisions\/49138"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=49057"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=49057"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=49057"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}