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dc.contributor.authorShroufi, A
dc.contributor.authorVan Custem, G
dc.contributor.authorCambiano, V
dc.contributor.authorBansi-Matharu, L
dc.contributor.authorDuncan, K
dc.contributor.authorMurphy, RA
dc.contributor.authorMaman, D
dc.contributor.authorPhillips, A
dc.date.accessioned2019-06-26T14:27:29Z
dc.date.available2019-06-26T14:27:29Z
dc.date.issued2019-04-16
dc.date.submitted2019-05-30
dc.identifier.issn1473-5571
dc.identifier.pmid31008798
dc.identifier.doi10.1097/QAD.0000000000002234
dc.identifier.urihttp://hdl.handle.net/10144/619400
dc.description.abstractBACKGROUND: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line antiretroviral treatment (ART) or do so after significant delay. For people on ART with a viral load (VL) > 1000 copies/ml, the World Health Organization (WHO) recommends a second VL measurement 3 months after the first VL and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated VL > 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality. METHODS: To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance to compare predicted outcomes of 2 policies, defining 1st-line regimen failure for patients on efavirenz based ART as either (i) two consecutive VL values > 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or (ii) a single VL value > 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second line ART. FINDINGS: The use of a single VL > 1000 copies/ml to define ART failure would lead to a higher proportion of persons with NNRTI resistance switched to second-line ART (65% vs 48%; difference 17% [90% range 14% - 20%]), resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6% - 30%; from a median of 3·1 to 2·5 per 100 person years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% Range 8% - 49%) among people on 1st line ART with a viral load > 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880,000 people with HIV), we estimate that this approach would lead to a median of 1,322 (90% range 67 to 3,513) AIDS deaths averted per year over three years. For South Africa this would represent around 10,215 deaths averted annually. INTERPRETATION: As a step towards reducing unnecessary mortality associated with delayed second line ART switch, defining failure of first-line efavirenz-based regimens as a single VL>1000 copies/ml should be considered. FUNDING: No specific funding was obtained for the analysis or writing of this manuscript.en_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Healthen_US
dc.rightsWith thanks to Wolters Kluwer Health.en_US
dc.titleSimplifying switch to second line ART: Predicted effect of defining failure of first-line efavirenz-based regimens in sub-Saharan Africa by a single viral load > 1000 copies/ml.en_US
dc.identifier.journalAIDSen_US
dc.source.journaltitleAIDS (London, England)
refterms.dateFOA2019-06-26T14:27:29Z


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