The Impact of Delayed Switch to Second-Line Antiretroviral Therapy on Mortality, Depending on Definition of Failure Time and CD4 Count at Failure

Abstract

Little is known about the functional relationship of delaying second-line treatment initiation for human immunodeficiency virus–positive patients and mortality, given a patient’s immune status. We included 7,255 patients starting antiretroviral therapy during 2004–2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting of marginal structural models. The nonlinear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation. We adjusted for measured time-varying confounding by CD4 count, viral load, and visit frequency. Five-year mortality was estimated to be 10.5% (95% CI: 2.2, 18.8) for immediate switch and to be 26.6% (95% CI: 20.9, 32.3) for no switch (51.1% if CD4 count was <100 cells/mm3). The hazard of death was estimated to be 0.37 (95% CI: 0.30, 0.46) times lower if everyone had been switched immediately compared with never. The shorter the delay in switching, the lower the hazard of death—delaying 30–59 days reduced the hazard by 0.53 (95% CI: 0.43, 0.65) times and 60–119 days by 0.58 (95% CI: 0.49, 0.69) times, compared with no switch. Early treatment switch is particularly important for patients with low CD4 counts at failure.

Improved detection and management of advanced HIV disease through a community adult TB‐contact tracing intervention with same‐day provision of the WHO‐recommended package of care including ART initiation in a rural district of Mozambique

“…Moreover, under routine programmatic conditions, participants that were clear suspects for ART failure (ART‐experienced individuals with TB and/or low CD4 counts) did not benefit from an ART switch during the 6‐month follow‐up period. WHO recommends expedited ART switch for AHD patients but this has not consistently translated into national recommendations, rather, patients with AHD usually endure the same long process of the general HIV‐positive population consisting of VL determinations repeated every three months, which is challenging in districts with non‐existent VL‐testing capacity [ 4 , 28 , 84 , 85 , 86 ]. The rollout of multi‐disease testing platforms such as GeneXpert which has POC‐VL capacity will increase the operationality of the recommended “package of care” for ART‐experienced patients with AHD [ 87 , 88 ].…”

High Prevalence of NRTI and NNRTI Drug Resistance Among ART-Experienced, Hospitalized Inpatients

“… 10 Switching a failing regimen early is effective at reducing mortality, especially in patients with low CD4 counts. 11 Yet, switching to a second-line regimen, particularly when protease inhibitors are used, is not always uniformly beneficial and may result in higher pill burden, potential side-effects, and poorer adherence. To assess the need for more rapid switching from first- to second-line regimens for seriously ill patients, we measured viremia and genotypic drug resistance (DR) in ART-experienced advanced HIV patients in 2 hospitals' inpatient departments in Kenya and Democratic Republic of Congo (DRC).…”

Time to Switch to Second-Line Anti-Retroviral Treatment and Its Predictors Among HIV Infected Adults with Virological Failure in Northwest Ethiopia: A Retrospective Follow-Up Study

“… 19 The same is true for the studies done in Uganda 17 and South Africa. 29 An increasing viral load count shows the degree of the severity of uncontrolled viral replication which in turn tells us impaired functionality of the first-line regimen. Virological treatment failure later leads to worsening immunologic and clinical conditions.…”