In poor countries, monitoring clinical events in patients on first line antiretroviral treatment (ART) is almost as effective in reducing mortality as using CD4 count or viral load measures to advise patients when to switch to second line ART. This means that limited access to the laboratory tests necessary for CD4 and viral load in impoverished settings should not significantly impede appropriate access to ART, which, according to the authors of an Article released on April 25, 2008 in The Lancet, should thus be expanded to all settings as soon as possible.
Two million patients are currently receiving combination ART in lower income countries, and this will continue for several years as laboratory services scale up. Therefore, the potential consequences of long-term use, including survival and the development of resistance to treatment, must be considered completely.
To attempt this, Professor Andrew Phillips, Royal Free and University College Medical School, University College London, UK, and colleagues employed a validated computer simulation model of HIV infection and the effects of ART. They used this model in a comparison of survival, the use of WHO recommended standard first and second-line ARTs, and the development of resistance that results from each of these different strategies.
They specifically analysed based on viral load, CD4 count, and clinical observation alone. In the viral load monitoring strategy, the second line treatment is recommended after the HIV viral load in the patient’s blood exceeds 500 copies per mililiter. This seemed to predict 83% survival after five years and 67% over 20 years. For CD4 cell count monitoring, the second line ART is initiated when the CD4 cell count in the blood drops below 50% of the peak levels; this predicted 82% and 64% survival respectively. Finally, clinical monitoring implies a switch to the second line when either two WHO stage 3 events or one WHO stage 4 event occurs. This method also showed an 82% predicted five year survival rate with a 64% rate for 20 years. These findings were robust, even when variations were introduced to the model and extensive sensitivity analyses were performed. Also, while survival was slightly longer with viral load monitoring, limited resource settings would not find it cost effective to use them.
In conclusion, the authors indicate that ART does not necessitate the use of advanced laboratory techniques for effective monitoring. “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 ARV therapy should be expanded to all settings as rapidly as possible; lack of access to laboratory monitoring should not be allowed to hinder this process.”
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, contributed an accompanying Comment in which they indicate that these results should reassure clinicians and patients in resource-limited settings with access to ART without advanced laboratory technologies. 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.”
Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model
Andrew N Phillips, Deenan Pillay, Alec H Miners, Diane E Bennett, Charles F Gilks, Jens D Lundgren
Lancet 2008; 371: 1443-51
Monitoring antiretroviral failure in resource-poor settings
David M Moore, Jonathan Mermin
Lancet 2008; 371: 1396-7
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Written by Anna Sophia McKenney