d4T + Indinavir + 3TC Vs d4T + Indinavir + ddI
In this study by a Spanish research group led by N. Villalba, 96 AZT-experienced patients with fewer than 350 CD4 cells/mm3 received standard doses of the nucleoside analog d4T in combination with the protease inhibitor indinavir with one of the following two 'nukes': either 3TC (150 mg twice daily) or ddI (in a once daily dose of 400mg). Data were presented through the nine month period, with the following results:
Absolute number and percentage of patients with 'undetectable' levels of HIV (under 500 copies by Chiron bDNA)
|Baseline||Month 1||Month 3||Month 6||Month 9|
Eight (11.4%) subjects in the 3TC arm and five (19.2%) in the ddI arm stopped treatment because of side effects.
The study methods were unscientific. For example, Villalba et al. did not say explicitly why so many more patients were enrolled on the 3TC arm. We might conclude that this was a non-randomized trial, or a chart-review. Why were no median baseline viral load data presented, nor were any statistical analyses offered? Adherence was not an issue? Why was a rather large group of patients (24%) undetectable at baseline? All of these factors may have skewed results for these patients, since the numbers of people whose viral load fell below detection at each timepoint are not consistent with (i.e., they are much poorer than) the results of other studies of the same or similar regimens. It is therefore difficult to draw any conclusions from this trial.
One virologic finding was worthy of note: by Month 3, the 184 codon mutation associated with resistance to 3TC was found in two-thirds of those on the 3TC arm who had not reached undetectable levels. In contrast, none of the subjects on the ddI arm who still had detectable virus at Month 3 had developed the 74 codon mutation associated with ddI resistance. This would suggest confirmation of the rapid development of 3TC resistance.