Integrase strand transfer inhibitors (INSTIs) have improved the treatment of human immunodeficiency virus (HIV). There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation
raltegravir,
elvitegravir, and second generation
dolutegravir and
bictegravir. The most recent INSTI,
cabotegravir, is approved for (1) treatment of
HIV infection in adults to replace current antiretroviral
therapy in individuals who maintain virologic suppression on a stable antiretroviral regimen without history of treatment failure and no known resistance to its components and (2) pre-exposure prophylaxis in individuals at risk of acquiring HIV-1
infection.
Cabotegravir can be administered intramuscularly as a monthly or bi-monthly injection depending on the indication. This long-acting combination has been associated with treatment satisfaction in clinical studies and may be helpful for individuals who have difficulty taking daily oral medications. Worldwide, second generation INSTIs are preferred for treatment-naïve individuals. Advantages of these INSTIs include their high genetic barrier to resistance, limited
drug-drug interactions, excellent rates of virologic suppression, and favorable tolerability. Few INSTI resistance-associated mutations have been reported in clinical trials involving
dolutegravir,
bictegravir and
cabotegravir. Other advantages of specific INSTIs include their use in various populations such as infants and children, acute
HIV infection, and individuals of childbearing potential. The most common adverse events observed in clinical studies involving INSTIs included
diarrhea,
nausea,
insomnia,
fatigue, and
headache, with very low rates of treatment discontinuation versus comparator groups. The long-term clinical implications of
weight gain associated with second generation INSTIs
dolutegravir and
bictegravir warrants further study. This review summarizes key clinical considerations of INSTIs in terms of clinical pharmacology,
drug-drug interactions, resistance, and provides perspective on clinical decision-making. Additionally, we summarize major clinical trials evaluating the efficacy and safety of INSTIs in treatment-naïve patients living with HIV as well as individuals at risk of acquiring
HIV infection.