Emerging Trends in the Long-Acting Antiretroviral Therapy: Current Status and Therapeutic Challenges

Abstract

Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of people living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to the build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in the fight against HIV. Few long-acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, long-acting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. Long-Acting Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease.