EMERGING RESISTANCE TO LONG-ACTING HIV ANTIRETROVIRALS: A SYSTEMATIC REVIEW OF CABOTEGRAVIR AND RILPIVIRINE DATA

The innovative use of long-acting antiretroviral therapy (ART), especially the injection of a blend of cabotegravir
(CAB-LA) and rilpivirine (RPV-LA), has positively impacted HIV management through improved patient
adherence and the elimination of the daily oral intake issue. Nevertheless, the latest findings show that cases of
resistance-associated virologic failure (RAVF) already have been in the picture despite the great efficacy of ART.
This review of literature's aim is to put together the existing knowledge regarding HIV drug resistance due to the
use of CAB-LA and RPV-LA in both treatment and pre-exposure prophylaxis (PrEP) contexts with regard to
biological mechanisms, prevalence, and risk factors. PRISMA 2020 method was followed for the literature search,
and databases searched were PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov,
and WHO ICTRP from 2015 to the projected year of 2025. The resistance that was found in the analysis of ten
major studies, which included the HPTN 083 and HPTN 084 trials, was very low but still significant—between
0.21% and 0.48% in controlled populations and about 0.35% from WHO surveillance globally. Instances of
mutations such as R263K, E138K/A, G118R, and Q148R/H/K were detected, resulting in a decrease of CAB
susceptibility by 3–8 times and also resistance against other integrase strand transfer inhibitors (INSTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The emergence of resistance was particularly associated
with the long intervals between or missed injections, the so-called tipping-point scenario in pharmacokinetics,
high viral load at baseline, diversity of HIV-1 subtype, and prior ART. Even though there are geographical
variations, the findings unambiguously indicate that the interplay of pharmacological, behavioral, and virological
factors promote and sustain resistance. Surveillance systems for resistance monitoring are still disjointed and
inconsistent in different regions, and genomic monitoring is hardly done in low- and middle-income countries. It
is imperative to bolster the global standardization in genotypic testing, adherence counseling, and
pharmacovigilance in order to preserve the long-term efficacy of CAB-LA and RPV-LA treatments. In the end,
the use of long-acting ART is giving the best and most revolutionary way to cope with HIV prevention and
treatment, but at the same time, attention and strategies to keep the patient cooperating should be put in place to
avoid the emergence and spread of HIV variants that are resistant.