Initiating Antiretrovirals in a Resource-Constrained Setting: Does One Size Fit All?
Address: Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India Email: Ajay Wanchu - firstname.lastname@example.org
Published: 8 August 2005 Journal of theInternational AIDS Society 2005, 7:67 This article is available from: http://www.jiasociety.org/content/7/3/67
The World Health Organization (WHO) aims to provide antiretroviral therapy (ART) to at least 3 million patients in resource-limited settings by the end of 2005, an initiative referred to as "3 by 5." The program uses a CD4+ cell count of 200 cells/microliter (mcL) for initiatingtreatment as a cutoff in asymptomatic individuals. Some issues need to be addressed when applying the program in resource-constrained countries such as India.
Limitations of WHO-Recommended Regimen Applied in India Reduction in viral load might reduce transmission of HIV. The combination of drugs primarily used in the WHO-approved regimen are nevirapine, lamivudine, and stavudine. This is thecheapest generic formulation in India that has the advantage of combining all 3 drugs in 1 pill. The cost of this combination is less than $1 per day. However, in the free treatment program, the number of patients who would require these medications worldwide will increase rapidly. Worldwide, 16,000 individuals get infected daily and each would, sooner, rather than later, require ART. In India,all of the 5 million-plus patients would be candidates for treatment. Do we have resources to provide medication even at less than $1 per day?
transmissibility of the virus decreases, but what are the options for those who develop resistance? In most instances, anyone who develops resistance today has few options because alternative regimens are far too costly. Because no baseline nevirapineresistance rates in treatment-naive patients are available in India, there is no knowledge about the percentage of individuals who are unlikely to respond to the ART offered by the 3 by 5 initiative in the first instance.
Can Treatment Be Deferred? Are we treating patients when they can do without ART? Can we defer treatment in asymptomatic patients? Perhaps we can. Western cutoffs to initiate ARTmay not be appropriate, as some studies have shown lower CD4+ cell counts in apparently healthy Indians. In one study, the range of CD4+ cell counts in healthy Indians started from just over 300 cells/mcL. Another study carried out in 200 healthy Indians showed that CD4+ cell counts ranged between 304 and 1864 cells/mcL. A modest decline early in the course of disease might qualify thepatient for initiation of ART. Can we wait longer until "chronic immune failure" develops, as early initiation means that patients lose their only therapeutic option much faster? Another issue relates to pitfalls in using guidelines where CD4+ cell counts decide treatment. Does one size fit all? Thus, while cytomegalovirus (CMV) infection develops most often with CD4+ cell counts < 50 cells/mcL, doeseveryone with a CD4+ cell count < 50 cells/mcL develop CMV disease? Surely no. Do we, then, treat everyone on the basis of a CD4+ cell count that tells us that an individual with CD4+ cell count < 200 cells/mcL is at heightened risk for opportunistic infections (OIs), even though a fraction do not develop OIs?
It is notable that although nevirapine-based regimens have been shown to do as well asother regimens, the drug has never been the "most preferred" in most international guidelines. The other issue is one of resistance with nevirapine, as a single amino acid substitution in the reverse transcriptase gene can result in resistance to the whole nonnucleoside reverse transcriptase inhibitor (NNRTI) class of drugs. Once resistance develops the
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