{"id":27169,"date":"2014-08-01T12:58:25","date_gmt":"2014-08-01T12:58:25","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=27169"},"modified":"2014-08-19T17:29:40","modified_gmt":"2014-08-19T17:29:40","slug":"27169","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/27169","title":{"rendered":"Pill A, Pill B: simplified second-line treatment for low-income countries"},"content":{"rendered":"

\"AIDSPolly Clayden, HIV i-Base<\/strong><\/p>\n

A one pill, once-daily fixed dose combination (FDC) second-line regimen might be feasible for low-income countries according to a clinical development programme presented at AIDS2014.<\/strong><\/p>\n

Anton Pozniak from the St Stephens Centre at Chelsea and Westminster Hospital, London showed plans for a simplified second-line regimen at a scientific workshop entitled: Research to measure success of antiretroviral use for prevention and treatment at individual and community levels. [1] The workshop was the first public presentation of the proposed second-line development programme.<\/p>\n

Currently, the preferred World Health Organisation (WHO) first-line regimen is a once-daily FDC of efavirenz plus tenofovir plus lamivudine or emtricitabine (EFV\/TDF\/3TC [or FTC]). Low cost, generic versions of this regimen are available and are simple to give in decentralised programmes by nurses and community health workers.<\/p>\n

The WHO preferred regimens for second-line antiretroviral treatment (ART) are PI-based (ritonavir-boosted lopinavir [LPV\/r] or atazanavir [ATV\/r]) with two new NRTIs. These regimens have several shortcomings including overlapping NRTI resistance, comparatively high pill count, twice-daily dosing (LPV\/r), NRTI toxicities and high cost compared to first-line treatment.<\/p>\n

The new proposal for people who fail first-line treatment with “Pill A” (EFV\/TDF\/3TC) is to develop “Pill B” – a once-daily heat-stable FDC of dolutegravir (DTG) plus optimised darunavir\/ritonavir (DRV\/r). Market forecasts suggest that Pill B might be available at low cost: US$250 per patient per year.<\/p>\n

Dr Pozniak explained that results from the original dose finding trials of DRV\/r, as well as a more recent one with 600\/100 mg, suggest that a dose reduction to DRV\/r 400\/100 mg might be feasible.<\/p>\n

The dose ranging (phase 2B) study for the proposed development programme would compare three once daily regimens: TDF\/FTC + DRV\/r 400\/100 mg vs DTG + DRV\/r 800\/100 mg vs DTG + DRV\/r 400\/100 mg. This phase would be conducted in treatment na\u00efve participants over 48 weeks.<\/p>\n

If 24-week phase 2B data justifies progression of the programme (no obvious safety or efficacy concerns), a 96-week phase 3 pivotal trial with 1050 NNRTI-experienced participants will follow.<\/p>\n

Phase 3 – a non-inferiority study conducted in sites in Africa, South East Asia and Eastern Europe – would compare 2NRTI+PI\/r (control arm) vs DTG + DRV\/r 800\/100 mg vs DTG + DRV\/r 400\/100 mg.<\/p>\n

Comment<\/h3>\n

The success of this programme should make switching people who are on current first-line regimens with virologic failure to second-line considerably simpler and more accessible.<\/strong><\/p>\n

The one criticism is that this would lead to recommending DTG second-line when many experts believe it should be the preferred first-line option in the future. It is critical that work is funded to ensure that we have enough information to use DTG first-line in low-income settings but research into first- and second-line DTG-based regimens should not be mutually exclusive. A better second line option is needed for the 5% of nearly 13 million people on first-line (and more as scaling up continues) that need to switch. Dr Pozniak noted that if a DTG\/TDF\/3TC (or even DTG\/TAF\/3TC) becomes the future Pill A, Pill B might be DRV\/r plus rilpivirine – which also needs to be investigated.<\/strong><\/p>\n

Research into optimising ART for low-income countries – usually discussed in small closed meetings -stepped out of the shadows at this conference including this presentation and results from a study with reduced dose AZT (see below).<\/strong> [2]<\/p>\n

We also summarise work on treatment optimisation in the 2014 Pipeline Report.<\/strong> [3]<\/p>\n

References:<\/p>\n

    \n
  1. Pozniak A. How can we evaluate simple sequences of first and second-line treatment in low-income countries? 20th International AIDS Conference. Melbourne. 20-25 July 2014. Workshop presentation TUWS1105.
    \nhttp:\/\/pag.aids2014.org\/session.aspx?s=1967<\/a>
    \n    http:\/\/pag.aids2014.org\/PAGMaterial\/PPT\/1486_1326\/melbourne_trials_pozniak_july14.pptx<\/a> (Slides)<\/li>\n
  2. Rougemont M et al. The MiniZID study: a randomized controlled trial on safety of reduced dose (400 mg) of zidovudine compared with standard dose (600 mg) in HIV-infected patients starting antiretroviral therapy. 20th International AIDS Conference. Melbourne. 20-25 July 2014. Poster abstract LBPE16.
    \n    http:\/\/pag.aids2014.org\/abstracts.aspx?aid=11206<\/a><\/li>\n
  3. Clayden P. Fit for purpose: treatment optimisation. i-Base\/TAG. 19 July 2014.
    \n    https:\/\/i-base.info\/htb\/26960<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base A one pill, once-daily fixed dose combination (FDC) second-line regimen might be feasible for low-income countries according to a clinical development programme presented at AIDS2014. Anton Pozniak from the St Stephens Centre at Chelsea and Westminster …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,38],"tags":[191],"class_list":["post-27169","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-treatment-access","tag-aids-20th-melbourne-2014"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27169","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=27169"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27169\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=27169"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=27169"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=27169"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}