July 10, 2001
This study was performed in Thailand by a research consortium from the Netherlands, Australia and Thailand. Resources for antiretroviral treatment are very limited in the developing world. Only sub-optimal regimens of antiretroviral drugs may be available. Strategies need to be developed to maximize the effectiveness of antiretrovirals in these settings. Though triple combination therapy has been the standard of care for HIV infection in developed countries for over five years, less active regimens had been extensively prescribed in the past.
One of the major barriers to full implementation of triple combination therapy in developing countries has been and continues to be cost. These therapies are expensive and out of reach of many individuals in these countries. This study attempts to examine whether a double combination regimen can be successfully used without switching to another combination in the absence of virological suppression.
The authors recruited seventy-one Thai HIV-positive patients who had been receiving a combination of d4T with ddI for a minimum of 48 weeks. Approximately half (31 of 68) were randomized to immediately switch to AZT with 3TC, while 37 were randomized to defer switching until further evidence of treatment failure occurred. They defined treatment failure as a one log rise in viral load or a decline of >30% of baseline CD4 count.
They found that there was a benefit in terms of treatment response between the two groups after an additional 96 weeks. Those who deferred the switch had a higher rate of undetectable viral loads (38% vs. 7%). Those who did switch immediately lost an average of 62 CD4 cells while those who deferred gained an average of 17 cells.
In other words, immediate switching from one sub-optimal regimen to another sub-optimal regimen was worse than delaying such a switch. The CD4 count at the time of randomization predicted whether or not an acceptable result would occur. A higher percentage of those with CD4 counts over 250 had an acceptable result compared to those with lower CD4 counts.
Indeed these baseline counts could be used to determine who gets what treatment (two-drug regimens for those with higher CD4 counts, three-drug regimens for those with lower CD4 counts). However, there wasn't any difference in the rate of HIV-related illnesses between the two groups in this time span (144 weeks total).
So what does this tell me? First, sub-optimal regimens remain sub-optimal. But in resource-poor settings sub-optimal regimens may be all that is available and can provide an acceptable rate of response (especially when compared to no treatment). Second, a dual nucleoside regimen such as d4T with 3TC can be continued for up to three years with reasonable treatment success at a reduced cost compared to highly active antiretroviral regimens.
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