{"id":44723,"date":"2023-02-01T07:37:26","date_gmt":"2023-02-01T07:37:26","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=44723"},"modified":"2023-04-10T19:04:53","modified_gmt":"2023-04-10T19:04:53","slug":"cabrpv-la-formulations-adverse-events-implementation-and-proms","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/44723","title":{"rendered":"Glasgow 2022: long-acting cabotegravir\/rilpivirine: adverse events, implementation and PROMs"},"content":{"rendered":"
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Kirk Taylor, HIV i-Base<\/strong><\/p>\n<\/div>\n

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\"\"<\/a><\/strong>HIV Drug Therapy Glasgow included several presentations on long-acting cabotegravir plus rilpivirine formulations (CAB+RPV-LA). Focus was given to adverse events, implementation and participant-reported outcomes (PROMs).<\/span><\/b><\/p>\n<\/div>\n

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Confirmed virologic failures (CVF) on phase 3 CAB+RPV-LA trials were evaluated and baseline rilpivirine resistance, HIV subtype A6\/A1, BMI >30 kg\/m2 and reduced CAB levels at week 4 were identified as risk factors. [1] Frequency of viral blips on CAB+RPV-LA were comparable to those observed on oral therapy and were not predictive of CVF. [2]<\/span><\/p>\n<\/div>\n

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Neuropsychiatric adverse events (NPAEs) were reported for 9% of participants on CAB+RPV-LA trials and the majority were classified as low grade (\u22642). [3] <\/span><\/p>\n<\/div>\n

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A survey of healthcare workers reported \u2018very\u2019 or \u2018extremely positive\u2019 views regarding implementation and delivery of long-acting antiretroviral therapy. [4]<\/span><\/p>\n<\/div>\n

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PROMs from phase 3 and real-world implementation studies consistently highlighted benefits of long-acting formulations for HIV therapy. [5-7]<\/span><\/p>\n<\/div>\n

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HPTN 083 reports efficacy of long-acting cabotegravir (CAB-LA) for high-risk gay men and transgender women. A 66% reduction of new HIV diagnoses was reported for those on CAB-LA. [8]<\/span><\/p>\n

Adverse events<\/h2>\n<\/div>\n
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Confirmed virologic failures (CVF) on CAB+RPV-LA therapy through week 48 of phase 3 trials were reported for 1.4% of participants (n=23). [1] CVF risk increased for participants with \u22652 baseline factors (RPV resistance mutations, BMI >30 kg\/m2 or HIV subtype A6\/A1).<\/p>\n<\/div>\n

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Participant data were pooled from FLAIR (124 weeks), ATLAS (96 weeks) and ATLAS-2M (152 weeks) for post-hoc analysis of risk factors. This analysis highlighted reduced week 4 CAB levels as an additional risk factor for CVF.<\/p>\n<\/div>\n

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A second study reported results from an exploratory analysis of viral blips using RNA samples collected during FLAIR and ATLAS-2M. [2] Blips occurred at similar frequencies for CAB+RPV-LA QM (12%), Q2M (8%) and QD oral therapy (17%). Snapshot analyses at weeks 96 (FLAIR) and 152 (ATLAS-2M) reported undetectable viral load for >90% of participants that had viral blips during the study period. Of the 17 reported CVFs on long-acting therapy, only one participant also experienced a viral blip during the trial. These findings suggest that viral blips are not predictive of CVF.<\/p>\n<\/div>\n

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NPAEs (e.g. headache, dizziness, depression and anxiety) have been reported for people taking CAB+RPV-LA. Post-hoc analysis of NPAEs that occurred on phase 3 studies (ATLAS, ATLAS-2M and FLAIR) was conducted to evaluate trends. [3] The frequency of drug-related NPAEs was 9% (n=111) for participants that received long-acting formulations. 96% of NPAEs were \u2264grade 2 and no drug-related grade 4 or 5 events were recorded. NPAEs occurred infrequently and events were mostly reported between weeks 4 to 12. Headache and dizziness tended to resolve within a week, whilst sleep and psychiatric disorders persisted for significantly longer.<\/p>\n<\/div>\n

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Participants with a history of psychiatric disorders or substance abuse were more likely to experience NPAEs. No serious drug-related NPAEs were reported across the study period. Participants were female (26%), Black (19%) and median age was 40 years (IQR 18 to 83).<\/p>\n

Implementation and PROMs<\/h2>\n<\/div>\n
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Healthcare workers were surveyed to ascertain perceptions of CAB+RPV-LA formulations and inform optimal implementation strategies. [4] Respondents were interviewed after a month (n=70) and again at one year (n=62). Most respondents were nurses (41%) and doctors (37%). Identified barriers included perceived risk of resistance (35%) and viral rebound (30%), lack of staff to administer injections (35%).<\/p>\n<\/div>\n

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Attitudes to implementation of CAB+RPV-LA were \u2018very\u2019 or \u2018extremely\u2019 positive after one year (76%). Side effects and being unable to administer injections at home were perceived as implementation barriers. 68% of healthcare providers wanted more information prior to trial initiation, but were positive about the benefits of long-acting formulations.<\/p>\n<\/div>\n

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Participants on ATLAS-2M were surveyed to evaluate experiences of injections, chronic therapy and treatment satisfaction. [5] Participants were female (27%), White (73%), median age was 42 years (IQR: 34 to 50) and 37% had previously received CAB+RPV-LA on the ATLAS trial.<\/p>\n<\/div>\n

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At three years, ISRs were rated as \u2018totally\u2019 or \u2018very acceptable\u2019 for 78% of participants. Treatment acceptance was ranked >80 on a scale of \u2018totally unacceptable\u2019 (0) to \u2018totally acceptable\u2019 (100). Treatment satisfaction was ranked from 0 to 66 and mean scores were >55 for participants on QM and Q2M regimens. Participants were satisfied with the convenience and flexibility of treatment but side effects, discomfort and pain scored negatively.<\/p>\n<\/div>\n

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Participants that missed at least one dose and received oral therapy during the trial period (n=70) were included in a sub-analysis. 88% of people in this group indicated a preference for long-acting therapies over oral regimens. These data may explain high retention and low discontinuation rates observed in ATLAS-2M.<\/p>\n<\/div>\n

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European participants on the CARISEL study (n=430) were surveyed to gauge their opinions on CAB+RPV-LA therapy. [6] Responses were scored on a five-point scale of \u2018completely disagree\u2019 (1) to \u2018completely agree\u2019 (5) at months 1, 4 and 12. Acceptability and feasibility scores were \u22654.5 at month 1 and moderately increased over time. Treatment satisfaction scores dipped at month 1 (-0.73, 95% CI -1.37 to -0.10) but improved to \u2265+2.84 at later timepoints. Most participants (91%) were positive about long-acting therapy at one year. Participants spent an average of 1 hour in the clinic and 75% agreed that this was acceptable.<\/p>\n<\/div>\n

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Whilst 31% of participants reported no challenges with LA therapy, negatives included ISRs (56%), missing work (13%) and travel schedules (9%). Not needing to carry medication, convenience and reduced stigma contributed to 99% of participants reporting a preference for LA formulations.<\/p>\n<\/div>\n

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Real-world data on the efficacy and adherence to Q2M CAB+RPV-LA were collected through the German CARLOS cohort study. [7] Participants (n=236) were male (95%) and median age was 43 years (IQR: 36 to 50). Baseline risk factors for CVF were recorded for 24 people and one person had 2 known risk factors. The primary reason for switch to long-acting therapy was participant request (92%).<\/p>\n<\/div>\n

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At six months, 89.5% of participants had undetectable viral load, 2% had \u226550 copies\/mL and there was one instance of CVF. The majority of drug-related AEs were low grade with a single grade 3 event of worsening anxiety. ISRs were common with 218 reports across 866 injections. Injections were delivered within the dosing widow for >97% of participants. Treatment satisfaction scores were 60.6 at six months.<\/p>\n<\/div>\n

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Cabotegravir as long-acting PrEP<\/h2>\n<\/div>\n
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HPTN 083 is a Phase 2b\/3 randomised controlled trial of PrEP formulations for gay men and transgender women at increased risk of HIV transmission risk. [8]<\/p>\n<\/div>\n

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Participants were recruited across 43 sites from 7 countries. CAB-LA was evaluated as an alternative to oral TDF\/FTC PrEP.<\/p>\n<\/div>\n

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A 66% reduction of new HIV diagnoses were observed for those receiving CAB-LA vs TDF\/FTC. There were 52 breakthrough cases of HIV that occurred in the first year after unblinding. Of these, diagnoses were more common on TDF\/FTC (n=34) than for CAB-LA (n=18).<\/p>\n<\/div>\n

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PK data indicated that CAB levels were mostly within range but one participant had rapid CAB clearance with unknown cause. For three cases, INSTI-associated resistance mutations were observed. CAB continues to show efficacy as a long-acting alternative to oral PrEP.<\/p>\n<\/div>\n

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

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  1. Orkin C et al. Expanded multivariable models to assist patient selection for long-acting cabotegravir + rilpivirine treatment: clinical utility of a combination of patient, drug concentration, and viral factors associated with virological failure over 152 weeks. HIV Drug Therapy Glasgow, October 23-26, 2022. Oral abstract O34.
    \n<\/span>https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_51.htm<\/a><\/span>\u00a0\u00a0<\/span><\/li>\n
  2. Latham C et al. HIV-1 RNA blips, low-level viral replication, and mean CD4+\/CD8+ ratio during phase 3\/3b cabotegravir + rilpivirine long-acting studies up to 152 weeks of therapy. P083. HIV Drug Therapy Glasgow, October 23-26, 2022. <\/span>Poster abstract P083.
    \n<\/span>    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_45.htm<\/a>
    \n    https:\/\/hivglasgow.org\/wp-content\/uploads\/2023\/01\/P083_Latham_Christine.pdf<\/a> (poster)<\/li>\n
  3. Elliot E et al. Drug-related neuropsychiatric adverse events across phase 3\/3b studies of long-acting cabotegravir + rilpivirine through week 48. HIV Drug Therapy Glasgow, October 23-26, 2022. <\/span>Poster abstract P168.
    \n<\/span>    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_46.htm<\/a><\/li>\n
  4. Slama L et al. Overcoming barriers and achieving optimal implementation of Cabotegravir and rilpivirine long-acting (CAB + RPV LA): staff study participant (SSP) results from the CAB + RPV implementation study in European locations (CARISEL). HIV Drug Therapy Glasgow, October 23-26, 2022. <\/span>Poster abstract P116.
    \n<\/span>    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_04.htm<\/a><\/span>
    \n    https:\/\/hivglasgow.org\/wp-content\/uploads\/2023\/01\/P116_Slama.pdf<\/a> (poster)
    \n<\/span><\/li>\n
  5. Chounta V et al. Patient-reported outcomes after 152 weeks of HIV maintenance therapy with long-acting cabotegravir + rilpivirine in the phase 3b ATLAS-2M study. HIV Drug Therapy Glasgow, October 23-26, 2022. <\/span>Poster abstract P070.
    \n<\/span>    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_32.htm<\/a><\/span>
    \n    https:\/\/hivglasgow.org\/wp-content\/uploads\/2023\/01\/P070_Spreen_William.pdf<\/a> (poster)
    \n<\/span><\/li>\n
  6. Lutz T et al. Perceptions of cabotegravir and rilpivirine long-acting (CAB + RPV LA) from patients in the CAB + RPV implementation study in European locations (CARISEL). HIV Drug Therapy Glasgow, October 23-26, 2022. <\/span>Poster abstract P123.
    \n<\/span>    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_29.htm<\/a><\/li>\n
  7. Borch J et al. 6-month outcomes of every 2 months long-acting cabotegravir and rilpivirine in a real-world setting – effectiveness, adherence to injections, and patient-reported outcomes of people living with HIV in the German CARLOS cohort. HIV Drug Therapy Glasgow, October 23-26, 2022. <\/span>Oral abstract O43.
    \n<\/span>    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_26.htm<\/a><\/li>\n
  8. Landovitz R. Laboratory analysis of HIV infections in the year 1 unblinded period of HPTN 083: injectable cabotegravir for PrEP in MSM and TGW. HIV Drug Therapy Glasgow, October 23-26, 2022. \u00a0Oral abstract.
    \n    https:\/\/www.natap.org\/2022\/Glascow\/GLASGOW_08.htm<\/a><\/li>\n<\/ol>\n<\/div>\n<\/div>\n
    \n

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

    Kirk Taylor, HIV i-Base HIV Drug Therapy Glasgow included several presentations on long-acting cabotegravir plus rilpivirine formulations (CAB+RPV-LA). Focus was given to adverse events, implementation and participant-reported outcomes (PROMs). Confirmed virologic failures (CVF) on phase 3 CAB+RPV-LA trials were evaluated …<\/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],"tags":[325],"class_list":["post-44723","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-hiv-16-glasgow-2022"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44723","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=44723"}],"version-history":[{"count":11,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44723\/revisions"}],"predecessor-version":[{"id":45251,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/44723\/revisions\/45251"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=44723"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=44723"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=44723"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}