The impact of delayed switch to second-line antiretroviral therapy on mortality, depending on failure time definition and CD4 count at failure
| Autor: | Matthew P. Fox, Michael Schomaker, Robin Wood, Andrew Boulle, Helen Bell-Gorrod, Frank Tanser, Mary-Ann Davies, Hans Prozesky |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
business.industry Treatment switch Confounding Marginal structural model Baseline data 01 natural sciences Antiretroviral therapy 3. Good health Inverse probability of treatment weighting 010104 statistics & probability 03 medical and health sciences 0302 clinical medicine Second line Internal medicine Medicine 030212 general & internal medicine 0101 mathematics business Viral load |
| ISSN: | 0002-9262 |
| DOI: | 10.1101/661629 |
| Popis: | BackgroundLittle is known about the functional relationship of delaying second-line treatment initiation for HIV-positive patients and mortality, given a patient’s immune status.MethodsWe included 7255 patients starting antiretroviral therapy between 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 (IPTW) of marginal structural models. The non-linear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation (TMLE). We adjusted for measured time-varying confounding by CD4 count, viral load and visit frequency.Results5-year mortality was estimated as 10.5% (2.2%; 18.8%) for immediate switch and as 26.6% (20.9%; 32.3%) for no switch (49.9% if CD4 count3). The hazard of death was estimated to be 0.40 (95%CI: 0.33-0.48) times lower if everyone had been switched immediately compared to never. The shorter the delay in switching, the lower the hazard of death, e.g. delaying 30-60 days reduced the hazard 0.52 (0.41-0.65) times, and 60-120 days 0.56 (0.47-0.66) times.ConclusionsEarly treatment switch is particularly important for patients with low CD4 counts at failure. |
| Databáze: | OpenAIRE |
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