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dc.contributor.authorShroufi, A
dc.contributor.authorVan Cutsem, 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.accessioned2019-08-20T16:30:21Z
dc.date.available2019-08-20T16:30:21Z
dc.date.issued2019-08-01
dc.date.submitted2019-08-15
dc.identifier.issn1473-5571
dc.identifier.pmid31305331
dc.identifier.doi10.1097/QAD.0000000000002234
dc.identifier.urihttp://hdl.handle.net/10144/619447
dc.description.abstractBACKGROUND: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 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 two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 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 viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor 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 first-line ART with a viral load more than 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 1322 (90% range 67-3513) AIDS deaths averted per year over 3 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 viral load more than 1000 copies/ml should be considered.en_US
dc.language.isoenen_US
dc.publisherWolters Kluwer Health/Lippincott Williams & Wilkinsen_US
dc.rightsWith thanks to Lippincott Williams & Wilkins.en_US
dc.titleSimplifying switch to second-line antiretroviral therapy in sub Saharan Africa: predicted effect of using a single viral load to define efavirenz-based first-line failure.en_US
dc.identifier.journalAIDSen_US
dc.source.journaltitleAIDS (London, England)
refterms.dateFOA2019-08-20T16:30:22Z


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