{"id":44131,"date":"2022-10-03T07:30:37","date_gmt":"2022-10-03T07:30:37","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=44131"},"modified":"2022-11-12T19:51:33","modified_gmt":"2022-11-12T19:51:33","slug":"low-levels-of-rpv-la-might-explain-failure-with-injectable-art-despite-perfect-adherence","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/44131","title":{"rendered":"Low levels of RPV-LA might explain failure with injectable ART despite perfect adherence"},"content":{"rendered":"
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Kirk Taylor, HIV i-Base<\/strong><\/p>\n<\/div>\n

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BHIVA guidelines caution that long-acting (LA) CAB\/RPV regimens have virologic failure rates of 1 in 70 at 12 months, rising to 1 in 60 at 24 months. Inter-person variability in PK parameters, especially of RPV-LA could be one explanation. [1]<\/span><\/b><\/p>\n<\/div>\n

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Early data from a sub-study of the Swiss HIV Cohort Study (SHCS) reports high inter-person variability in Cmin \u00ad<\/sub>levels for CAB and RPV. Whilst Cmin values were above their respective IC90<\/sub> levels, some readings were close to this threshold prompting concerns about safety and efficacy. [2]<\/span><\/p>\n<\/div>\n

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Therapeutic dose monitoring (TDM) can help to identify real-world variations in PK parameters to inform dosing and monitoring intervals. <\/span><\/p>\n<\/div>\n

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The ATLAS-2M and FLAIR studies showed that LA-CAB\/RPV can effectively manage HIV but real-world PK data is also required outside of stringent clinical studies. This prospective observational sub-study of the SHCS reports LA-CAB\/RPV PK data in people living with HIV.<\/span><\/p>\n<\/div>\n

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Most PK samples (84%) were collected prior to Q8W dosing when participants were expected to be close to Cmin levels. Blood samples were collected at routine visits (n=61) or during the oral lead-in period (n=30). In line with Swiss treatment guidelines, two participants who were on Q4W schedules transitioned to Q8W regimens. <\/span><\/p>\n<\/div>\n

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Inter-participant variability of Cmin was reported as 101% and 94% for CAB and RPV, respectively. Intra-participant variability was significantly lower at 50% for CAB (p=0.002) and 27% for RPV (p<0.0001). The range of Cmin values for CAB and RPV was approximately 250 to 1,100 ng\/mL and 18 to 300 ng\/mL, respectively. <\/span><\/p>\n<\/div>\n

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All reported PK values exceeded the IC90 values for CAB (166 ng\/mL) and RPV (12 ng\/mL). However, RPV levels were close to the IC90 for some participants, raising concerns of efficacy and safety.<\/span><\/p>\n<\/div>\n

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Data collected up to July 2022 (n=46) were from participants who were female (17%), with median age of 45 years (range: 28 to 62), Caucasian (63%), Black (13%), Hispanic (7%) or Asian (7%). HIV viral load was below 200 copies\/mL for all participants and <50 copies\/mL (94%). Median CD4 count was 667 cells\/mm3<\/sup> (range: 191 to 1192). <\/span><\/p>\n<\/div>\n

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BHIVA guidelines indicate that obesity can be a risk factor for virologic failure on LA-CAB\/RPV regimens. Median BMI was 26 kg\/m2<\/sup> (range: 19 to 37) with 15% and 54% classified as obese and overweight, respectively. <\/span><\/p>\n<\/div>\n

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Low grade adverse events, such as injection site reactions, were reported by 30% of participants. No virologic failures were reported.<\/span><\/p>\n<\/div>\n

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comment\u00a0 <\/span><\/h3>\n<\/div>\n
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Currently, based on the current BHIVA guidelines, a large proportion of people are contraindicated from using CAB-LA\/RPC\/LA due to obesity. <\/span><\/strong><\/p>\n<\/div>\n

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Although the risk of viral failure was lower with monthly dosing, the added inconvenience of more frequent injections make this an unlikely choice, even if it was recommended in guidelines.<\/span><\/strong><\/p>\n<\/div>\n

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The study aims to enrol 200-300 people over the next two years.<\/span><\/strong><\/p>\n<\/div>\n

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References<\/span><\/p>\n<\/div>\n

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  1. Waters L et al. Interim BHIVA guidance on long-acting cabotegravir\/rilpivirine (LA-CAB\/RPV) for antiretroviral therapy. (07 Feb 2022).
    \n<\/span>https:\/\/www.bhiva.org\/hiv-1-treatment-guidelines<\/a><\/li>\n
  2. Thoueille P et al. Real-life therapeutic concentration monitoring of long-acting cabotegravir and rilpivirine: preliminary results of an ongoing prospective observational study in Switzerland. Pharmaceutics 14(8). (29 July 2022).
    \n    https:\/\/doi.org\/10.3390\/pharmaceutics14081588<\/a><\/span>\u00a0\u00a0<\/span><\/li>\n<\/ol>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

    Kirk Taylor, HIV i-Base BHIVA guidelines caution that long-acting (LA) CAB\/RPV regimens have virologic failure rates of 1 in 70 at 12 months, rising to 1 in 60 at 24 months. Inter-person variability in PK parameters, especially of RPV-LA could …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,36],"tags":[],"class_list":["post-44131","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals","category-drug-resistance"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44131","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=44131"}],"version-history":[{"count":8,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44131\/revisions"}],"predecessor-version":[{"id":44364,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44131\/revisions\/44364"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=44131"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=44131"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=44131"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}