HIV integrase inhibitors

General characteristics and mechanism of action

Integrase inhibitors represent a relatively new, but critically important group of antiretroviral agents. In modern pharmacology, this class of drugs is actively studied, and a significant portion of new molecules with a similar mechanism of action are still in the development and clinical trial stages.

The primary task of these drugs is to interrupt the viral life cycle at one of its most critical stages. The mechanism of action of the group consists in preventing integration. The term "integration" in this context means the physical insertion of viral DNA into the genomic DNA of the host cell. By blocking this process, the drugs deprive the virus of the ability to use the genetic machinery of the infected cell to produce new viral particles.

Pharmacodynamics and indications using raltegravir as an example

The primary and most studied representative of this group in our course is the drug raltegravir, also known under the trade name Isentress. From a pharmacodynamic perspective, its direct target is the integrase enzyme. Raltegravir does not simply bind to the enzyme, but specifically blocks its catalytic core. Deprived of an active catalytic core, the enzyme loses its function, and the viral DNA remains in the cytoplasm, unable to penetrate the genome.

Regarding indications for use, it is important for students to avoid typical mistakes on exam tests. Raltegravir is indicated for the treatment of HIV infection in adult patients. At the same time, it is equally effective against both type 1 HIV infection (HIV-1) and type 2 HIV infection (HIV-2). Test questions often prompt you to choose only one of the types or add nonexistent options (e.g., type 3), so remember clearly: the drug works against both major types of the human immunodeficiency virus.

Pharmacokinetics and the effect of diet

The pharmacokinetic profile of raltegravir has one striking feature that a future physician must know in order to properly counsel patients. The drug is administered exclusively orally. However, its absorption and final blood concentration critically depend on the patient's diet.

A key pharmacokinetic parameter — bioavailability — exhibits a pronounced dependence on the presence of fats in food. If a patient takes the drug with a fatty meal, the bioavailability of raltegravir increases approximately twofold compared to administration on an empty stomach or with low-fat food. This twofold increase is a classic example of a food-drug interaction in pharmacology that must be accounted for when prescribing a treatment regimen.

Safety profile and tolerability

Despite the severity of the disease and the complexity of the mechanism of action, integrase inhibitors in general, and raltegravir in particular, feature a very favorable safety profile. Good tolerability of the drug by the majority of adult patients is noted in clinical practice.

Nevertheless, like any pharmacological agent, raltegravir can cause a number of side effects. The most frequent adverse reactions include:

• Headache;
• Nausea;
• Fatigue.

Knowledge of these three main side effects will help you not only successfully answer pharmacology questions, but also promptly recognize adverse reactions in a patient during a medical appointment.

Class and exam questions

What else to study on this topic

• Prospects of the class: what other integrase inhibitors are in development.
• Molecular structure of the catalytic core of the integrase enzyme.
• Mechanisms of changes in drug bioavailability upon interaction with fatty foods.
• Comparative characteristics of the course and therapy of HIV-1 and HIV-2.

Other topics in the "Antivirals" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.