Switch strategies in antiretroviral therapy regimens

Abstract

Despite great advances in antiretroviral therapy in the last decade, several limitations still remain such as adverse effects, lack of adherence and drug–drug interactions. Switching antiretroviral therapy in stable, virologically suppressed patients with the aim of improving tolerability and convenience is an expanding strategy in clinical practice. Several factors need to be taken into consideration when switching a suppressive regimen, such as previous virologic failure, genetic barrier of the new regimen, prior duration of virologic suppression and expected level of adherence. The most frequently used strategies include reductions in the number of pills, drugs or doses. Although switching strategies may be useful, not all the regimens used in clinical practice are based on data from randomized clinical trials and some may not be the best option for certain patients; therefore, therapy should be individualized taking into consideration available information as well as patient and drug characteristics.

Keywords::

• antiretroviral therapy
• HIV
• monotherapy
• simplification
• switch

Financial & competing interests disclosure

E Van den Eynde has received honoraria for lectures from Boehringer Ingelheim, GSK, Viiv, Pfizer, BMS, Abbott, Gilead, Janssen and Merck. D Podzamczer has received research grants and/or honoraria for advisories and/or conferences from Boehringer Ingelheim, GSK, Viiv, Pfizer, BMS, Abbott, Gilead, Janssen and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Modifying the antiretroviral regimen in virologically suppressed patients might help to avoid drug-related toxicities and improve treatment convenience.

• The main goal of the switch must be maintaining viral suppression.

• The duration of virologic suppression prior to the switch is important for success of the new regimen.

• Switching antiretroviral therapy in treatment-experienced patients with archived resistance mutations is not exempt of the risk of virologic failure.

• Fully active nucleoside reverse transcriptase inhibitors must be included as a part of the new regimen when switching a ritonavir-boosted protease inhibitors (PI/r) to unboosted atazanavir, non-nucleoside reverse transcriptase inhibitors (NNRTIs), or integrase inhibitors.

• Switching from PI/r regimens to unboosted atazanavir, NNRTIs or raltegravir improves the lipid profile.

• Replacement of tenofovir by abacavir generally maintains viral suppression and may result in bone mineral density and renal function improvements.

• Switching from efavirenz to nevirapine or etravirine generally improves CNS symptoms and maintains viral suppression.

• Substitution of PIs/r or NNRTIs by elvitegravir-based treatment appears to be effective and safe and may result in improvements in symptoms and toxicity.

• Monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with no history of PI failure and having a strict adherence, generally maintains viral suppression and might be helpful for selected patients to avoid nucleoside reverse transcriptase inhibitor-related toxicities and to reduce cost.

• Dual therapy simplification strategies deserve further investigation and randomized clinical trials.

Notes