Happy Ten Year AnniversarySep 11th, 2007 | By Jonathan Golob | Category: Medicine
… to triple drug therapy for HIV.
While the new therapy started in 1996, it was on September 11th 1997 when the first report was published in the New England Journal of Medicine. Here is a lovely manuscript–a proper randomized double-blind and controlled study.
The trial patients were grouped by CD4 T cell counts, and then randomized to triple drug therapy or the controls of single or double drug therapy. Initially, the study was to last 52 weeks. When the results started to roll in, the blinding was ended and everyone allowed access to the triple drug cocktail.
At the time the language both cautious and astounded,
The three-drug combination of indinavir, zidovudine, and lamivudine reduced the viral load in serum to less than 500 copies per milliliter for up to one year in more than 80 percent of the HIV-infected patients we studied, all of whom had prior antiretroviral therapy. Most patients in the three-drug group whose HIV RNA levels were reduced to less than 500 copies per milliliter also had less than 50 RNA copies per milliliter when the ultrasensitive investigational assay was used. The sustained response in HIV RNA levels with the three-drug therapy was superior to that with either indinavir monotherapy or the combination of zidovudine and lamivudine. No prior antiretroviral regimen has produced the marked, sustained decreases in viral load achieved with this three-drug combination.
Finally, physicians were able to reduce viral loads to near undetectable levels. The researchers didn’t even consider this a cure, rather a path to “delayed progression to AIDS and prolonged survival.” At the time, it wasn’t clear if reducing HIV viral loads would really help patients avoid AIDS; by the end of the short study, CD4 T cell levels had only started to increase.
The dissociation between the marked decreases in viral load and the incomplete restoration of CD4 cell counts in the three-drug group remains unexplained. Some patients may have ongoing, slower increases in CD4 cell counts after six months of therapy. In patients with autoimmune disease or cancer who receive intensive radiation therapy or chemotherapy, CD4 cell counts recover slowly and may take three years or more to reach normal levels.30,31 Further study is needed to determine what level of restoration of CD4 cell number and function can ultimately be attained with the three-drug regimen. It remains to be seen whether the immune system can be fully reconstituted even when regimens that achieve maximal HIV suppression are used.
The scientists ended with a prescient thought. “Without complete viral suppression, antiretroviral regimens will probably select for drug-resistant mutants, leading to the failure of therapy,” they cautioned.
So, happy ten years of highly effective anti-retroviral therapy.