Management of HIV-infected patients with multidrug-resistant virus

Abstract

Heavily pretreated HIV-infected patients with multidrug-resistant virus remain a clinical challenge to the treating physician. While the goal of therapy in such patients is still controversial, sustained immunologic and clinical benefit have only been demonstrated with complete suppression of plasma viral load below detectable levels. Expert use of resistance testing may help in the selection of the salvage regimen, and monitoring of plasma drug levels may help optimize the potency and tolerability, especially of complex, multiple drug regimens where adherence remains a critical determinant of treatment outcome. The potential roles of newer agents, adjuvants, treatment interruptions, and immune-based therapies remain under investigation.

Resistance evolution in HIV — Modeling when to intervene

“…The index i may be considered to vary between i = 0 for a treatment-naive patient to a maximum value of i = 7 for a patient who has exhausted all available antiviral regimens. The maximum index value depends on the particular sequence of regimens chosen, and on average is closer to three than seven [26]. The total time to failure is ${\sum }_{i=0}^3{T}_i$; it is this quantity which we would like to maximize.…”

“…The emergence of resistance to one drug often leads to cross-resistance to other drugs of the same family. Cross-resistance is particularly common within the NNRTI class where a single point mutation confers resistance to all NNRTIs [26]. Although the situation is more complicated within the NRTI class, high-level phenotypic resistance to one drug commonly confers partial cross-resistance to most other NRTIs.…”