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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.
AIDS. 2019 08 01; 33(10):1635-1644.AIDS

Abstract

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.

Authors+Show Affiliations

Médecins Sans Frontières, Cape Town, South Africa.Médecins Sans Frontières, Cape Town, South Africa.Institute for Global Health, UCL, London, UK.Institute for Global Health, UCL, London, UK.Médecins Sans Frontières, Cape Town, South Africa.Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, USA.Médecins Sans Frontières, Cape Town, South Africa.Institute for Global Health, UCL, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31305331

Citation

Shroufi, Amir, et al. "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." AIDS (London, England), vol. 33, no. 10, 2019, pp. 1635-1644.
Shroufi A, Van Cutsem G, Cambiano V, et al. 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. AIDS. 2019;33(10):1635-1644.
Shroufi, A., Van Cutsem, G., Cambiano, V., Bansi-Matharu, L., Duncan, K., Murphy, R. A., Maman, D., & Phillips, A. (2019). 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. AIDS (London, England), 33(10), 1635-1644. https://doi.org/10.1097/QAD.0000000000002234
Shroufi A, et al. 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. AIDS. 2019 08 1;33(10):1635-1644. PubMed PMID: 31305331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Shroufi,Amir, AU - Van Cutsem,Gilles, AU - Cambiano,Valentina, AU - Bansi-Matharu,Loveleen, AU - Duncan,Kristal, AU - Murphy,Richard A, AU - Maman,David, AU - Phillips,Andrew, PY - 2019/7/16/entrez PY - 2019/7/16/pubmed PY - 2019/7/16/medline SP - 1635 EP - 1644 JF - AIDS (London, England) JO - AIDS VL - 33 IS - 10 N2 - 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. SN - 1473-5571 UR - https://www.unboundmedicine.com/medline/citation/31305331/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 L2 - https://doi.org/10.1097/QAD.0000000000002234 DB - PRIME DP - Unbound Medicine ER -
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