Promptly switching antiretroviral therapy (ART) when individuals have viral rebound saves lives, Aidsmap reports an important study has found. Delayed switching more than doubled the risk of death over five years and was especially dangerous when a person had a CD4 cell count below 100. The research led by Michael Schomaker at the Centre for Infectious Disease Epidemiology and Research, University of Cape Town and Institute of Public Health, University for Health Sciences Medical Informatics and Technology (UMIT), involved people in South Africa who received ART between 2004 and 2017.
“We have shown that an early switch of regimen is highly beneficial in terms of reduced mortality,” comment the authors. “Patients with low CD4 counts at time of failure are at particularly high risk of increased mortality, whereas a moderate delay in healthy patients comes with a comparatively lower risk.”
The research is of immediate significance to ART treatment programmes in South Africa and other resource-limited settings. The investigators suggest that individuals with a detectable viral load should have their CD4 cell count measured regularly (currently guidelines do not recommend CD4 cell monitoring in stable ART-treated individuals). They also emphasise that a delay between a first and confirmatory test of virological failure is associated with increased mortality risk.
“Our study highlights that it often takes a long time to switch patients to second line treatment in South Africa,” comment Dr Bell-Gorrod and colleagues. “It is no surprise that delayed treatment switch may affect patient’s health. However, according to our results, earlier switch is of particular benefit when switching after the first signs of failure – the first viral load > 1000 copies/ml, for those who go onto confirmed failure.”
The investigators acknowledge that doctors may be reluctant to switch patients who have problems with adherence. However, in other instances, rapid treatment changes are likely to be beneficial.
“Our study highlights the importance of early treatment switch, particularly for patients with low CD4 cell counts at failure,” conclude the researchers.
Abstract
Little is known about the functional relationship of delaying second-line treatment initiation for HIV-positive patients and mortality, given a patient’s immune status. We 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. 5-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 count<100 cells/mm3). 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. Early treatment switch is particularly important for patients with low CD4 counts at failure.
Authors
Helen Bell-Gorrod, Matthew P Fox, Andrew Boulle, Hans Prozesky, Robin Wood, Frank Tanser, Mary-Ann Davies, Michael Schomaker
[link url="http://www.aidsmap.com/news/apr-2020/delaying-treatment-changes-when-first-line-art-fails-costs-lives-says-south-african"]Full Aidsmap report[/link]
[link url="https://academic.oup.com/aje/advance-article-abstract/doi/10.1093/aje/kwaa049/5812654?redirectedFrom=fulltext"]American Journal of Epidemiology abstract[/link]