Helen Bell Gorrod1, Richard Court2, Michael Schomaker3,4, Gary Maartens2, Richard A Murphy5,6,7. 1. Health Economics and Decision Science (HEDS), School for Health and Related Research, University of Sheffield, Sheffield, United Kingdom. 2. Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa. 3. Institute of Public Health, Medical Decision Making and Health Technology Assessment, UMIT-University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria. 4. Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. 5. Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA. 6. Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA; and. 7. David Geffen School of Medicine at UCLA, Los Angeles, CA.
Abstract
BACKGROUND: After failure of first-line antiretroviral therapy (ART) in the public sector, delayed or missed second-line ART switch is linked with poor outcomes in patients with advanced HIV. SETTING: We investigated delayed or missed second-line ART switch after confirmed virologic failure in the largest private sector HIV cohort in Africa. METHODS: We included HIV-infected adults with confirmed virologic failure after 6 months of nonnucleoside reverse-transcriptase inhibitor-based ART. We estimated the effect of timing of switch on the hazard of death using inverse probability of treatment weighting of marginal structural models. We adjusted for time-dependent confounding of CD4 count, viral load, and visit frequency. RESULTS: Five thousand seven hundred forty-eight patients (53% female) with confirmed virologic failure met inclusion criteria; the median age was 40 [interquartile range (IQR): 35-47], advanced HIV was present in 48% and the prior duration of nonnucleoside reverse-transcriptase inhibitor-based ART was 1083 days (IQR: 665-1770). Median time to confirmation of virologic failure and to second-line switch was 196 (IQR: 136-316) and 220 days (IQR: 65-542), respectively. Switching to second-line ART after confirmed failure compared with remaining on first-line ART reduced risk of subsequent death [adjusted hazard ratio: 0.47 (95% confidence interval: 0.36 to 0.63)]. Compared with patients who experienced delayed switch, those switched immediately had a lower risk of death, regardless of CD4 cell count. CONCLUSIONS: Delayed or missed switch to second-line ART after confirmed first-line ART failure is common in the South African private sector and associated with mortality. Novel interventions to minimize switch delay should be tested and not limited to those with advanced disease at treatment failure.
BACKGROUND: After failure of first-line antiretroviral therapy (ART) in the public sector, delayed or missed second-line ART switch is linked with poor outcomes in patients with advanced HIV. SETTING: We investigated delayed or missed second-line ART switch after confirmed virologic failure in the largest private sector HIV cohort in Africa. METHODS: We included HIV-infected adults with confirmed virologic failure after 6 months of nonnucleoside reverse-transcriptase inhibitor-based ART. We estimated the effect of timing of switch on the hazard of death using inverse probability of treatment weighting of marginal structural models. We adjusted for time-dependent confounding of CD4 count, viral load, and visit frequency. RESULTS: Five thousand seven hundred forty-eight patients (53% female) with confirmed virologic failure met inclusion criteria; the median age was 40 [interquartile range (IQR): 35-47], advanced HIV was present in 48% and the prior duration of nonnucleoside reverse-transcriptase inhibitor-based ART was 1083 days (IQR: 665-1770). Median time to confirmation of virologic failure and to second-line switch was 196 (IQR: 136-316) and 220 days (IQR: 65-542), respectively. Switching to second-line ART after confirmed failure compared with remaining on first-line ART reduced risk of subsequent death [adjusted hazard ratio: 0.47 (95% confidence interval: 0.36 to 0.63)]. Compared with patients who experienced delayed switch, those switched immediately had a lower risk of death, regardless of CD4 cell count. CONCLUSIONS: Delayed or missed switch to second-line ART after confirmed first-line ART failure is common in the South African private sector and associated with mortality. Novel interventions to minimize switch delay should be tested and not limited to those with advanced disease at treatment failure.
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