Antiretroviral Therapy - Guidelines (cont.)
Shifting guidelines on starting therapy date back to a time when the issues were whether or not to use zidovudine and whether therapy should be started at less than 200 or less than 500 CD4 cells/uL. While the regimens have changed since then, the lack of convincing data on the optimal time to start therapy has not. Moreover, it is unlikely that a study will ever be performed that will definitively demonstrate when treatment should be initiated. Therefore, the recent modification in recommendations could be looked at as either a positive or negative reflection on the state-of-the-art of antiretroviral treatment. I will explain why I see the shift as a positive reflection.
The rationale for deferring therapy comes from several key observations made during the last few years. First, we now know it is highly unlikely that current therapies will be able to eradicate the virus from the body. Thus, life-long treatment is required for HIV. Second, current therapies are associated with significant short-term toxicity, such as nausea, diarrhea, and fatigue, as well as long-term toxicity. The long-term toxicity includes peripheral neuropathy and metabolic abnormalities such as diabetes and increased cholesterol levels. Additionally, many people have an even greater concern that antiretroviral therapy may be contributing to certain body changes that have been described, such as sunken cheeks, thinning of the arms and legs, and an increase in waist size. A third observation leading to the trend in delaying treatment is that many individuals are not able to strictly adhere to the therapy for a many year duration. What's more, this non-compliance results in drug resistance and, ultimately, treatment failure.
Although the above issues are all important, I would argue that a compelling reason to consider deferring therapy is related to the success of current antiretroviral treatments. Yes, some data suggests that the virologic response to treatment is better in those who start early. Studies are not convincing, however, that a difference in response exists between those starting treatment at less than 350 versus 350 to 500 CD4 cells/uL. Furthermore, there is even a question among experts as to how convincing the data is that starting at 200 to 350 is better than starting at less than 200 CD4 cells/uL. Finally, increasing evidence suggests that even severely immunosuppressed individuals experience substantial immunologic improvement after starting treatment. Accordingly, the modifications in the current recommendations for when to start antiretroviral therapy should, at least in part, be seen as a tribute to the potency of current regimens, and not simply a response to their limitations.