Choosing appropriate pharmacotherapy for drug-resistant HIV

ABSTRACT

Introduction: Despite the potency of current antiretrovirals, some patients continue to struggle with the management of the treatment of HIV due to drug resistance-associated mutations. The underlying causes of these developments are usually drug adherence and drug availability as well as the economic affordability of those potent drugs in low to middle-income countries as well as in some industrialised countries. Viral replication, despite therapy, varies by region from 5 to 28. Non-adherence includes a variety of behaviours with different clinical implications. Addressing non-adherence and choosing new regimens based on a strategic vision may aid overall treatment strategies in the future.

Areas covered: The authors review the literature derived from Embase, MEDLINE and the main international congresses on transmitted and selected drug resistance to HIV therapeutics. They also consider the pharmacological aspects of antiretroviral therapy including the genetic barrier, convenience, potency, drug-drug interactions and tolerability are discuss prospective randomized or observational clinical trials on salvage therapy.

Expert opinion: Preventive intervention is the most efficient way to reduce the selection and transmission of drug-resistant mutations. While subjects with no current available options may benefit from new compounds (ibalizumab and fostemsavir), strategies should be implemented to spare as many patients as possible from drug resistance.

KEYWORDS:

• HIV
• resistance
• interactions
• adherence
• strategic
• antiretroviral

Article highlights

• The accumulation of drug-resistant mutations correlate with poorer life expectancy in people living with HIV.

• Virologic failure to antiretroviral therapy is multi-factorial (i.e.: drug-drug interactions, adherence, drug availability, lifestyle, linguistic and cultural barriers, possible exposure to superinfection) and factors leading to failure should be recognized and corrected when possible to avoid repeated exposure to failure and accumulation of resistance.

• The individualized choice of a regimen is favoured by the diverse tolerability and pharmacokinetic characteristics of HIV drugs, as well as by the improvement in efficacy and tolerability profiles of newer drugs. Counselling remains an indispensable step.

• Timely intervention of intolerance symptoms and/or viral rebound reduces the risk of accumulating mutations.

• Whenever adherence remains an issue, high-genetic barrier drugs and drug classes not involved current pipelines for future antiretrovirals should be preferred to spare those drugs that will be formulated as long-acting compounds. Old drugs can still be useful ones.

• When resistance to all commercial drug classes has happened, every effort should be made to allow the patient to be treated with the latest and emerging drug classes, through early access or named patient programs or through clinical trials, even if this may mean changing treatment.

• The most promising drugs for patients with resistance issues are ibalizumab and fostemsavir.

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Declaration of interest

In the past 36 months, G Rizzardini has received personal grant support from participating on the advisory boards of Merck Sharp and Dohme, Gilead Sciences, ViiV Healthcare and AbbVie while A Capetti has received personal grant support for participating on the advisory boards of Merck Sharp and Dohme, Gilead Sciences and ViiV Healthcare. 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.

Reviewer disclosures

One peer reviewer is an employee of CAPRISA. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.