Atazanavir (Reyataz®) is a
protease inhibitor (PI) for the treatment of
HIV infection. Several trials have demonstrated the good efficacy and toxicity profile of
atazanavir boosted by
ritonavir (
atazanavir/r). However, several toxicity events and pharmacokinetic issues due to
drug-to-drug interactions (partly related to
ritonavir) may complicate
atazanavir/r
therapy. This is why regimens with unboosted
atazanavir have been experimented with and are used in clinical practice. The aim of this article is to identify the clinical settings in which unboosted
atazanavir may be a safe and effective option for the long-term control of HIV replication. Despite the fact that a favourable
lipid profile and good gastrointestinal tolerability have been reported in comparative trials, unboosted
atazanavir should not be considered an optimal choice for treatment-naive patients. In fact, boosting with
ritonavir produces higher
atazanavir plasma levels, which are beneficial in terms of efficacy, especially in untreated patients with high plasma HIV
RNA. Clinical data indicate that, in patients with sustained undetectable HIV
RNA and without previous virological failure or HIV drug resistance-associated mutations, a switch to unboosted
atazanavir-based regimens is a feasible option to control and prevent toxicity events, especially in patients who cannot tolerate
ritonavir and in those with severe hyperbilirubinaemia on
atazanavir/r. Moreover, while unboosted
atazanavir must not be used in pregnant women, it is a recommended option in special populations, such as patients with moderate
liver insufficiency. Lastly, unboosted
atazanavir in combination with
raltegravir may allow the construction of a well tolerated and effective regimen without
nucleoside reverse transcriptase inhibitors in patients for whom these drugs are contraindicated. In conclusion, there is a good rationale, significant clinical interest and accumulating clinical experience with unboosted
atazanavir-based regimens, although this formulation should be used only in specific situations and as a maintenance strategy. Moreover, therapeutic
drug monitoring could be useful in specific circumstances (such as in patients with liver impairment or in case of potential
drug-drug interactions).