{"id":46065,"date":"2023-09-01T07:44:15","date_gmt":"2023-09-01T07:44:15","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=46065"},"modified":"2025-05-06T17:39:36","modified_gmt":"2025-05-06T17:39:36","slug":"chapas-4-supports-better-second-line-options-for-children","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/46065","title":{"rendered":"IAS 2023: CHAPAS-4 supports better second-line options for children"},"content":{"rendered":"
\n

Polly Clayden, HIV i-Base<\/span><\/b><\/p>\n<\/div>\n

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\"\"<\/p>\n

Tenofovir alafenamide (TAF)\/emtricitabine (FTC) and dolutegravir (DTG) were virologically superior to abacavir (ABC) or zidovudine (AZT)\/lamivudine (3TC) and boosted lopinavir (LPV\/r) and atazanavir (ATV\/r), respectively, in the second-line paediatric CHAPAS-4 trial. <\/span><\/b><\/p>\n

These findings were shown at IAS 2023. [1]<\/span><\/b><\/p>\n<\/div>\n

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There are limited options and formulations for second-line ART available for children living with HIV. The current LPV\/r-based standard of care needs to be taken twice daily. And although TAF has been highlighted as a priority agent for children (who cannot use TDF because of renal and bone toxicity), this has been based on limited evidence.\u00a0 <\/span><\/p>\n<\/div>\n

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CHAPAS-4 (Children with HIV in Africa: Pharmacokinetics and Acceptability of Simple novel second-line antiretroviral agents) looked at long-term outcomes for children switching from NNRTI-based first-line to second-line ART. The trial evaluated a number of options.<\/span><\/p>\n<\/div>\n

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It was a 4×2 factorial open-label trial, conducted in Uganda, Zambia and Zimbabwe.<\/span><\/p>\n<\/div>\n

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A total of 919 children and adolescents, aged 3\u201315 years, failing first-line ART, were randomised to TAF\/FTC vs ABC or AZT\/3TC (standard of care) and in turn to DTG vs DRV\/r vs ATV\/r vs LPV\/r (standard of care). All were dosed according to WHO weight bands. <\/span><\/p>\n<\/div>\n

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The primary endpoint was viral load <400 copies\/mL at week-96. The investigators hypothesised: TAF\/FTC would be non-inferior to standard of care (10% margin); ATV\/r non-inferior to LPV\/r (12% margin); DRV\/r and DTG superior to LPV\/r and ATV\/r arms combined (superiority threshold p=0.03, as multiple comparisons). The primary analysis was intention-to-treat.<\/span><\/p>\n<\/div>\n

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Participants were 54% male, median age 10 years, CD4 669 cells\/mm3<\/sup> and viral load 17,573 copies\/mL. They had been on first-line ART for a median of 5.6 years: 53% received ABC and 47% AZT and 57% efavirenz (EFV) and 44% nevirapine (NVP0.<\/span><\/p>\n<\/div>\n

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Over 96 weeks only 11 (1.2%) participants were lost to follow up and 98% of time was spent on the original allocated regimen; 5 (0.5%) started third-line ART.\u00a0<\/span><\/p>\n<\/div>\n

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At week-96, TAF\/FTC was superior to ABC or AZT: 89.4% vs 83.3% respectively viral load <400 copies\/mL (p=0.004). ATV\/r was non-inferior to LPV\/r (p=0.33). DTG was superior to LPV\/r and ATV\/r: 92% vs 82.5% respectively viral load <400 copies\/mL (p<0.0001). DRV\/r showed a trend to superiority to LPV\/r and ATV\/r (p=0.04).<\/span><\/p>\n<\/div>\n

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These effects were similar for viral load <60 copies\/mL, at weeks 48 and 144, by per-protocol analysis and by subgroup analyses (first-line NRTIs and NNRTIs, sex, weight and CD4)\u00a0\u00a0\u00a0 <\/span><\/p>\n<\/div>\n

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CD4 count improved in all participants \u2013 there was no difference by arms. <\/span><\/p>\n<\/div>\n

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There was no difference in adverse events (AE) between NRTIs. There were more grade 3\/4 AE, mostly hyperbilirubinemia, ATV\/r vs LPV\/r (p<0.0001). DTG had fewer AE vs LPV\/r (p=0.02).<\/span><\/p>\n<\/div>\n

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There was increased total and LDL cholesterol in LPV\/r\u00a0 vs other arms (p<0.001 and p=0.0002, respectively) <\/span><\/p>\n<\/div>\n

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Improvement in growth parameters were greater with TAF and with DTG. Participants on LPV\/r had the least weight gain.<\/span><\/p>\n<\/div>\n

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There was no excess weight gain with DTG and TAF.<\/span><\/p>\n<\/div>\n

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comment<\/span><\/h3>\n<\/div>\n
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A generic formulation containing TAF for children has been on the WHO PADO priority list for some time now, so these supporting data from CHAPAS are very welcome. [2]<\/span><\/strong><\/p>\n<\/div>\n

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This needs to be either a dual formulation combined with 3TC or FTC or a fixed dose triple combination with additional DTG, to be used over WHO weight-bands 3\u201325 kg. \u00a0These formulations would give alternatives to ABC-based regimens and mean that all age groups have access to a tenofovir-based regimen. The triple fixed-dose combination could be used in both first- and second-line paediatric treatment and both formulations would be good news as the dual combination could also be used with DRV\/r.<\/span><\/strong><\/p>\n<\/div>\n

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The ongoing UNIVERSAL project includes pharmacokinetic (PK) modelling and bioavailability studies of TAF and DTG\/TAF\/3TC dose ratio. [3]<\/span><\/strong><\/p>\n<\/div>\n

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A recent announcement from Gilead stated that the company (originator manufacturer of F\/TAF) will provide a technology transfer of currently available data for a dispersible formulation of F\/TAF and supporting PK data. [4]\u00a0 <\/span><\/strong><\/p>\n<\/div>\n

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PENTA (within the UNIVERSAL project) will develop the PK modelling and clinical studies, and CHAI, will be in charge of the global access strategy, in collaboration with two generic manufacturers.<\/span><\/strong><\/p>\n<\/div>\n

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Progress has also been made in developing a DRV\/r fixed-dose combination (120 mg of DRV plus 20 mg of ritonavir) for second-line treatment in children with resistance to DTG, within this initiative.<\/span><\/strong><\/p>\n<\/div>\n

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These plans are aligned with the WHO Global Accelerator for Pediatric Formulation (GAP-f). [5] \u00a0<\/span><\/strong><\/p>\n<\/div>\n

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

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    \n
  1. Musiime V et al. Increasing second-line antiretroviral therapy options for children with HIV in Africa: week-96 efficacy and safety results of the CHAPAS-4 randomised trial. <\/span><\/span>IAS 2023. Brisbane. Australia. 23\u201326 July 2023. Oral abstract 5764.
    \n<\/span>https:\/\/ias.reg.key4events.com\/key4register\/AbstractList.aspx?e=96&preview=1&aig=-1&ai=52421<\/a> (abstract)
    \n    https:\/\/conference.ias2023.org\/media-1110-track-b-late-breaker<\/a> (webcast)<\/li>\n
  2. WHO. <\/span>Priorities for antiretroviral drug optimization in adults and children report of a CADO, PADO and HIVResNet joint meeting. 25 July 2022.
    \n    https:\/\/www.who.int\/publications\/i\/item\/9789240053038<\/a><\/li>\n
  3. UNIVERSAL.
    \n    https:\/\/universalproject.org<\/a><\/li>\n
  4. Gilead press release. Gilead partners with CHAI and Penta to improve treatment and adherence rates among children with HIV in low and middle income countries. 13 July 2023.
    \n    https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2023\/7\/gilead-partners-with-chai-and-penta-to-improve-treatment-and-adherence-rates-among-children-with-hiv-in-low-and-middle-income-countries<\/a><\/li>\n
  5. WHO. Global Accelerator for Paediatric Formulations Network (GAP-f)
    \n    https:\/\/www.who.int\/initiatives\/gap-f<\/a><\/li>\n<\/ol>\n

    This report was first published on 9 August 2023.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Tenofovir alafenamide (TAF)\/emtricitabine (FTC) and dolutegravir (DTG) were virologically superior to abacavir (ABC) or zidovudine (AZT)\/lamivudine (3TC) and boosted lopinavir (LPV\/r) and atazanavir (ATV\/r), respectively, in the second-line paediatric CHAPAS-4 trial. These findings were shown at …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[],"class_list":["post-46065","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/46065","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=46065"}],"version-history":[{"count":2,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/46065\/revisions"}],"predecessor-version":[{"id":51024,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/46065\/revisions\/51024"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=46065"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=46065"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=46065"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}