Optimal Antiviral Switching to Minimize Resistance Risk in HIV Therapy

Abstract

The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

Switching Strategies to Mitigate HIV Mutation

“…We also consider SWATCH treatment [20], [21]. The rationale behind this strategy is that one could preempt virologic rebound and reduce accumulating drug-resistant genotypes by alternating treatments.…”

Resistance evolution in HIV — Modeling when to intervene

“…We consider interventions of the type described in [18]–[20] to modulate the value of v ( T i – 1 ), which affects both P ( P i ) and E ( T i P ). The methods described in these papers are theoretically able to consistently reduce v ( T i – 1 ) from the nominal value of 18,500 virus/ml to less than 50 virus/ml using optimal control-based applications of previously failed antiviral agents.…”

Use of In Vitro to In Vivo Extrapolation to Predict the Optimal Strategy for Patients Switching from Efavirenz to Maraviroc or Nevirapine

“…For this reason, lead-in dosing of nevirapine (200 mg for 14 days, increasing to 200 mg twice daily thereafter in adults) is recommended, but it is unclear whether such dosing results in a window of sub-therapeutic nevirapine concentrations following a switch from efavirenz to nevirapine [13][14][15][16][17].…”