{"id":36563,"date":"2019-08-23T08:40:05","date_gmt":"2019-08-23T08:40:05","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=36563"},"modified":"2019-08-23T11:12:14","modified_gmt":"2019-08-23T11:12:14","slug":"high-efficacy-from-switching-to-bictegravir-f-taf-in-virally-suppressed-participants-including-analyses-by-baseline-drug-resistance","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/36563","title":{"rendered":"Switching to bictegravir\/F\/TAF in virally suppressed participants \u2013 including analyses by baseline drug resistance"},"content":{"rendered":"

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

Several studies at IAS 2019 presented data on switching to bictegravir\/FTC\/TAF (B\/F\/TAF).<\/span><\/strong><\/p>\n

Paul Sax from <\/span>Brigham and Women’s Hospital, Boston, presented results from a randomised double-blind phase 3 study (4030) switching people with undetectable viral load on stable dolutegravir (DTG)-based ART (plus either FTC\/TDF or TFC\/TAF).<\/p>\n

The study randomised565 participants to B\/F\/TAF (n=284) or DTG+F\/TAF (n=281). Although history of integrase resistance was an exclusion criteria, documented drug resistance to NRTI, NNRTI and protease inhibitors was allowed. <\/span><\/p>\n

Approximate baseline characteristics included median age 50 years (IQR: 20 to 79), 85% men. 70% white, 22% Black\/African and 22% Hispanic\/Latino. Median CD4 count was about 640 cells\/mm3<\/sup>(IQR: 460 to 885).<\/span><\/p>\n

At week-48, viral load was <50 copies\/mL by snapshot analysis in 93% vs 91% in the B\/F\/TAF vs DTG+F\/TAF arms respectively. The results for primary endpoint of viral failure (>50 copies\/mL) was <1% vs 1% (n=1 vs 3), meeting criteria for non-inferiority (diff. \u20130.7%, 95% CI: \u20132.8 to 1.0) using 4% margin. Sensitivity analyses using <20 copies\/mL cut-off reported undetectable viral load in 91% vs 86% overall and 64% vs 60% for target not detected\u00a0(B\/F\/TAF vs DTG + F\/TAF). <\/span><\/p>\n

Adverse events were similar between arms, including leading to drug continuation (n=6 in each arm (2.1%) and including grade 3.4 laboratory abnormalities. No significant differences in lipids were reported between arms with similar use of lipid lowering drugs at baseline through to week-96.<\/span><\/p>\n

There were also no differences in rates of viral suppression between arms in the 24% participants with previous NRTI resistance: K65R or >2 thymidine analogue mutations (TAMS) (94% vs 93%) or other NRTI (87% vs 87%). No participants in either group with previous NRTI resistance developed detectable viral load over 48 weeks and there were no newly emergent integrase-related mutations. Further results on drug resistance in this study were included in a separate poster. [2]<\/span><\/p>\n

Another two posters provided similar reports of viral suppression with baseline drug resistance.<\/span><\/p>\n

Andreatta et al looked at drug resistance in 510 participants in the control arms of two switch studies who rolled over into the open label extension (OLE) to receive <\/span>B\/F\/TAF for a median of 60 weeks (IQR: 48 to 72). [3]<\/span><\/p>\n

Cumulative baseline genotypic data were available for NRTI in 73% (373\/510) and integrase in 49% (248\/510), with primary mutations in 11% (41\/373) and 3.6% (9\/248), for NRTI and integrase respectively. DNA genotyping detected previously undocumented M184V\/I in 5.4% (20\/373), and TAMs were observed in 8.0% (30\/373).<\/b><\/span><\/p>\n

However,<\/span>99% (503\/510) of participants had viral load < 50 copies\/mL at last visit, including 95% (19\/20) with archived M184V\/I, 100% (30\/30) with TAMs, and 100% (9\/9) with integrase resistance. No new resistance was detected during the OLE in the five participants who met criteria for resistance testing.<\/span><\/p>\n

Acosta et al presented a second poster looked at low level baseline resistance using deep sequencing in 1270 treatment-naive participants in a further two studies. [4]<\/span><\/p>\n

Additional primary resistance mutations not found by population sequencing were detected in 3.7%, 3.7%, 4.2% and 5.8% for NRTI, integrase, NNRTI and PI-associated mutations, respectively. Overall, participants with low-frequency resistance mutations had viral load < 50 copies\/mL at week 96 at similar rates similar to the overall study.<\/p>\n

In women, Cissy Kityo from the Joint Clinical Research Centre in Kampala presented results 96-week phase 3 results from 470 women on stable selected ART regimens who were randomised (1:1) to either switch to once-daily B\/F\/TAF or remain on their current ART. At week-48, participants in the control arm were switched to B\/FTAF until week-96. [5]<\/span><\/p>\n

This was an open-label study with sites in the Dominican Republic, Russian Federation, Thailand, Uganda, and the US. Baseline regimens at entry was elvitegravir\/cobicistat\/F\/TAF (54%), E\/C\/F\/TDF (43%) or atazanavir + ritonavir + F\/TDF (5%).<\/span><\/p>\n

Baseline characteristics at randomisation included median age 40 years (range: 21 to 64), median CD4 count 701 cells\/mm3<\/sup>(IQR: 539 to 895) and baseline eGFR was 100 (IQR: 83 to 117). Ethnicity included black\/African (37%), white (28%), Asian (22%) and Hispanic\/Latino (15%). Only six women had viral load that was detectable >50 copies\/mL.<\/span><\/p>\n

Although B\/F\/TAF looks to have produced high rates or viral suppression these results were presented as as Missing = Excluded analysis (M=E), rather than by more strict Missing=Failure (M=F) analyses. Unsurprisingly, >98% virologic outcomes were reported for both timepoints in both arms (as on-treatment analyses tend to do). For example, 234 women were originally randomised to B\/F\/TAF but at week-96 the denominator for the 99.5% success reported is based on only 208 women (207 of whom had viral load <50 copies\/mL). <\/span><\/p>\n

Side effects were reported for almost the whole study (462\/470) but only for the time on B\/F\/TAF (ie without the week-48 results from the control arm.<\/span><\/p>\n

Overall, most side effects were grade 1\/2. Grade 3\/4 adverse events (AEs) were reported by 7% (n-31\/462) of women using B\/F\/TAF, with 6% (n=27\/462) judged related to study drugs. Serious AEs were reported by 5% (24\/462) but only led to one study discontinuation.<\/span><\/p>\n

No new cases of drug resistance were reported to B\/F\/TAF in either group through to week-96. One person on E\/C\/F\/TAF in the control arm with viral rebound and the M184V mutation resuppressed after switching to B\/F\/TAF.<\/span><\/p>\n

Small improvements were linked switching from TDF-containing combinations to TAF and although no lipid changes were reported as significant, again, this was only reported for B\/F\/TAF exposure and not for the control arm at week 48.<\/span><\/p>\n

Finally, Jean-Michel Molina from Saint Louis Hospital, Paris, presented 24-week results in 86 HIV positive participants older than 65 years who switched to open-label B\/F\/TAF from E\/C\/F\/TAF or a TDF-based regimens. Follow-up in this study will continue out to week 96.<\/span><\/p>\n

Baseline characteristics included: <\/span>mean age 70 years (range 65-80), 13% were female, and 99% were white. Median weight was 78 kg (range: 49 to 110) and eGFR was 76 mL\/min (range: 40 to 130). Baseline ART was E\/C\/F\/TAF for\u00a0 91% (78\/86) of participants.<\/p>\n

At week-24, 98% participants remained <50 copies\/mL, again using Missing=Excluded (M=E) analysis – as 2 participants had missing data and 2 discontinued (with last viral load <5- copes\/mL).<\/span><\/p>\n

Tolerability was good with no grade 3\/4 events and no change in weight, although median eGFR declined by \u20134.5 mL\/min at week 12 and was then stable out to week 24.<\/span><\/p>\n

comment<\/span><\/h3>\n

These studies support high efficacy of B\/F\/TAF as a switch option in different populations including continued viral suppression with baseline mutations.<\/span><\/strong><\/p>\n

It is unclear why results are being presented as observed rather than full intent-to-treat analyses, when at least both should be presented.<\/span><\/strong><\/p>\n

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

    \n
  1. Sax P et al. <\/span>Switching to a single-tablet regimen bictegravir, emtricitabine, and tenofovir alafenamide (B\/F\/TAF) from dolutegravir (DTG) plus emtricitabine and either tenofovir alafenamide or tenofovir disoproxil fumarate (F\/TAF or F\/TDF). 10th IAS Conference on HIV Science. Mexico City, Mexico. 21\u201324 July 2019. Oral abstract MOAB0105.
    \n<\/span>http:\/\/programme.ias2019.org\/Abstract\/Abstract\/1225<\/span><\/a><\/li>\n
  2. Acosta R et al. <\/span>Keeping the pressure on archived NRTI resistance: Switching to bictegravir\/emtricitabine\/tenofovir alafenamide (B\/F\/TAF) triple therapy in study 4030. 10th IAS Conference on HIV Science. Mexico City, 21\u201324 July 2019. P<\/span>oster abstract MOPEB241.
    \n    http:\/\/programme.ias2019.org\/Abstract\/Abstract\/3907<\/a><\/li>\n
  3. Andreatta K et al. Previously undocumented preexisting resistance and maintenance of virologic suppression in HIV-1 RNA-suppressed patients switching to Bictegravir\/Emtricitabine\/Tenofovir Alafenamide (B\/F\/TAF). <\/span>10th IAS Conference on HIV Science. Mexico City, 21\u201324 July 2019. Poster abstract MOPEB243.
    \n<\/span>    http:\/\/programme.ias2019.org\/Abstract\/Abstract\/721<\/span><\/a><\/li>\n
  4. Acosta R et al. <\/span>Low-frequency resistance variants in ART-na\u00efve participants do not affect bictegravir\/emtricitabine\/tenofovir alafenamide (B\/F\/TAF) triple therapy treatment outcome. 10th IAS Conference on HIV Science. Mexico City, 21\u201324 July 2019. Poster abstract MOPEB242.
    \n<\/span>    http:\/\/programme.ias2019.org\/Abstract\/Abstract\/3778<\/a><\/b><\/span><\/li>\n
  5. Kityo C et al. Longer-term (96-week) efficacy and safety of switching to bictegravir\/emtricitabine\/tenofovir alafenamide (B\/F\/TAF) in women. 10th IAS Conference on HIV Science. Mexico City, Mexico. 21\u201324 July 2019. Oral abstract MOAB0106<\/span>.
    \n<\/span>    http:\/\/programme.ias2019.org\/Abstract\/Abstract\/1210<\/span><\/a><\/li>\n
  6. Molina J-M et al. \u00a0<\/span>A phase 3b, multicenter, open-label study switching from an Elvitegravir\/Cobicistat\/Emtricitabine\/Tenofovir Alafenamide(E\/C\/F\/TAF) or a Tenofovir disoproxil fumarate containing regimen to Bictegravir\/Emtricitabine\/Tenofovir Alafenamide (B\/F\/TAF) in virologically-suppressed, HIV-1 infected subjects aged \u226565 years. 10th IAS Conference on HIV Science. Mexico City, 21\u201324 July 2019. P<\/span>oster abstract MOPEB238.
    \n    http:\/\/programme.ias2019.org\/Abstract\/Abstract\/1453<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Several studies at IAS 2019 presented data on switching to bictegravir\/FTC\/TAF (B\/F\/TAF). Paul Sax from Brigham and Women’s Hospital, Boston, presented results from a randomised double-blind phase 3 study (4030) switching people with undetectable viral load …<\/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":[273],"class_list":["post-36563","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-ias-10-mexico-city-2019"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/36563","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=36563"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/36563\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=36563"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=36563"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=36563"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}