Simplifying 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.

Abstract

BACKGROUND: 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.