Simplifying 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.
Journal
AIDSAbstract
BACKGROUND: 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.PubMed ID
31305331Language
enISSN
1473-5571ae974a485f413a2113503eed53cd6c53
10.1097/QAD.0000000000002234
Scopus Count
Collections
Related articles
- Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines.
- Authors: Phillips AN, Bansi-Matharu L, Venter F, Havlir D, Pozniak A, Kuritzkes DR, Wensing A, Lundgren JD, Pillay D, Mellors J, Cambiano V, Jahn A, Apollo T, Mugurungi O, Ripin D, Da Silva J, Raizes E, Ford N, Siberry GK, Gupta RK, Barnabas R, Revill P, Cohn J, Calmy A, Bertagnolio S
- Issue date: 2020 Mar
- Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa.
- Authors: Evans D, Hirasen K, Berhanu R, Malete G, Ive P, Spencer D, Badal-Faesen S, Sanne IM, Fox MP
- Issue date: 2018 Apr 10
- SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa.
- Authors: Amstutz A, Nsakala BL, Vanobberghen F, Muhairwe J, Glass TR, Achieng B, Sepeka M, Tlali K, Sao L, Thin K, Klimkait T, Battegay M, Labhardt ND
- Issue date: 2018 Feb 12
- Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes: a multicentre cohort study.
- Authors: Hermans LE, Moorhouse M, Carmona S, Grobbee DE, Hofstra LM, Richman DD, Tempelman HA, Venter WDF, Wensing AMJ
- Issue date: 2018 Feb
- BREATHER (PENTA 16) short-cycle therapy (SCT) (5 days on/2 days off) in young people with chronic human immunodeficiency virus infection: an open, randomised, parallel-group Phase II/III trial.
- Authors: Butler K, Inshaw J, Ford D, Bernays S, Scott K, Kenny J, Klein N, Turkova A, Harper L, Nastouli E, Paparini S, Choudhury R, Rhodes T, Babiker A, Gibb D
- Issue date: 2016 Jun