Monitoring of clinical events in patients on first line antiretroviral treatment (ART) in poor countries is almost as effective in terms of survival as using CD4 count or viral load measures at advising when to switch to second line ART. Thus lack of access to the laboratory tests for CD4 and viral load in poor settings should not be allowed to hinder access to and roll-out of ART, which needs to be expanded to all settings as soon as possible. These are the conclusions of authors of an Article in this week's edition of The Lancet.
Clinical monitoring is being used for most of the two million patients currently receiving combination ART in lower-income countries and will continue to be used for many years, as the scale-up of laboratory services lags behind ART provision. Therefore it is important to fully consider the potential long-term consequences of its use, especially in terms of survival and the development of resistance to ART.
Professor Andrew Phillips, Royal Free and University College Medical School, University College London, UK, and colleagues used a validated computer simulation model of HIV infection and the effect of ART to compare survival, use of WHO-recommended standard first and second-line ART, and development of resistance that result from the three different strategies – based on viral load, CD4 count or clinical observation alone.
They found that, roughly speaking, the percentage of patients surviving five years is predicted to be 83% in patients using the viral load monitoring strategy (switch to second line when HIV viral load in patient's blood goes over 500 copies per ml), 82% with CD4 cell count monitoring (switch to second line when CD4 cell count in blood drops 50% from peak) and 82% with clinical monitoring (switch to second line when two new WHO stage 3 events* occur or one WHO stage 4 event* occurs). The corresponding values over 20 years were 67%, 64%, and 64%. The researchers found their findings were robust even when variations in the model were introduced and extensive sensitivity analyses were done. They also found that, although survival was slightly longer with viral load monitoring, this strategy would not be cost effective in most resource limited settings.
The authors conclude: "In summary, our results suggest that use of ARV therapy without monitoring of viral load or CD4 cell count does not have marked detrimental effects on patient survival or on development of resistance. This finding is particularly relevant in view of the limited array of anti-retroviral combinations available to the developing world. Access to ART should be expanded to all settings as rapidly as possible; lack of access to laboratory monitoring should not be allowed to hinder this process."
In an accompanying Comment, Dr David Moore, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada, and Dr Jonathan Mermin, Coordinating Center for Global Health, US Centers for Disease Control and Prevention, Nairobi, Kenya, say that the study should provide reassurance to the many clinicians and patients in resource-limited settings who have access to ART but not to the complex laboratory technologies that accompany HIV treatment in industrialised countries. They say: "Investments should continue to be made to improve health-care infrastructure in resource-limited settings and to develop laboratory methods that are low cost and technologically undemanding to support antiretroviral therapy programmes."
Notes to editors: *WHO stage 3 event= episode of an HIV-related disease indicative of severe immunosuppression, like pulmonary Tuberculosis or severe bacterial pneumonia; WHO stage 4 event = an episode of advanced HIV disease considered equivalent to an AIDS-defining clinical event
Professor Andrew N Phillips, Royal Free and University College Medical School, University College London, UK T) + 44 (0) 7738 181457 E) a.phillips@pcps.ucl.ac.uk
Dr David Moore, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada T) 1-604-806-8477 E) dmoore@cfenet.ubc.ca
http://multimedia.thelancet.com/pdf/press/outcomes.pdf
Journal
The Lancet