This paper presents an approach that predicts the effectiveness of HIV combination therapies by simultaneously addressing several problems affecting the available HIV clinical data sets: the different treatment backgrounds of the samples, the uneven representation of the levels of therapy experience, the missing treatment history information, the uneven therapy representation and the unbalanced therapy outcome representation. The computational validation on clinical data shows that, compared to the most commonly used approach that does not account for the issues mentioned above, our model has significantly higher predictive power. This is especially true for samples stemming from patients with longer treatment history and samples associated with rare therapies. Furthermore, our approach is at least as powerful for the remaining samples.