- What are integrase strand-transfer inhibitors (INSTIs) in antiretroviral therapy (ART) for HIV infection?
- What is antiretroviral therapy for HIV infection?
- What is HIV infection?
- How do integrase strand-transfer inhibitors work in antiretroviral therapy for HIV infection?
- What are the major side effects of INSTIs?
- What are the FDA-approved INSTIs and their side effects?
What are integrase strand-transfer inhibitors (INSTIs) in antiretroviral therapy (ART) for HIV infection?
Integrase strand-transfer inhibitors (INSTIs) are one of the latest additions to the classes of drugs used in antiretroviral therapy (ART) for human immunodeficiency (HIV) infection. The first integrase strand-transfer inhibitor came into use in 2007, as part of the ART regimen with nucleoside reverse transcriptase inhibitors (NRTIs).
INSTIs are often a part of fixed-dose, single pill, combination drug formulations for ART. INSTIs, as a part of a complete ART regimen, are approved for treatment of children with HIV infection, who are 12 or older and weigh at least 40 kg.
INSTIs are effective as initial therapy in controlling viral growth in treatment-naive HIV patients. INSTIs are also used to reduce the viral load in treatment-experienced patients, who develop resistance to multiple other antiretroviral drug classes.
What is antiretroviral therapy for HIV infection?
Antiretroviral therapy is a treatment regimen for HIV infection, using a combination of three or more drugs that prevent viral replication at different stages in its replication cycle. HIV infection has no cure, but ART can effectively control viral growth and keep an HIV infected person healthy and active for many years.
What is HIV infection?
HIV infection is caused by a virus that infects and weakens the human immune system. The virus enters a human immune cell known as T-cell, and uses its cell machinery to replicate itself.
Without treatment, HIV infection in its later stages can progress to acquired immune deficiency syndrome (AIDS), when the immune system is so severely impaired it is unable to fight even common infections effectively.
How do integrase strand-transfer inhibitors work in antiretroviral therapy for HIV infection?
HIV is a microscopic scrap of genetic matter that consists of a single strand of RNA encased in a protein capsule. Viruses are incapable of reproducing on their own; they use the machinery of a living host cell to replicate themselves.
There are several stages in the process of HIV’s replication. Once the virus enters through the cell membrane into the T-cell’s cytoplasm (fluid inside the cell), it converts its RNA strand into a double-strand DNA using an enzyme known as reverse transcriptase.
The viral DNA then releases another enzyme known as integrase, which transports the viral DNA strand into the T-cell’s nucleus and inserts it into the T-cell’s DNA. Once integrated with the host DNA, the virus can build the necessary protein chain to create more viral particles.
The integrase strand-transfer inhibitors bind metallic ions at the insertion site in the T-cell DNA, preventing the viral DNA strand transfer by the integrase enzyme. The viral DNA is then degraded and cannot multiply.
The INSTIs have a high barrier to resistance development by HIV, especially the second generation INSTIs. INSTI resistance may still develop gradually with HIV mutations.

QUESTION
What is HIV? See AnswerWhat are the major side effects of INSTIs?
INSTIs are relatively safe and better-tolerated than other HIV drugs. Some of the common side effects are:
Following are some rarer side effects:
- Muscle damage (myopathy)
- Skeletal muscle breakdown (rhabdomyolysis)
- Malignant tumors
- Kidney damage
- Hypersensitivity reactions
- Depression and suicidal thoughts
What are the FDA-approved INSTIs and their side effects?
Following are the two FDA-approved INSTIs that are currently part of antiretroviral therapy, and some of their common side effects:
Raltegravir (Isentress, Isentress HD)
Available as tablets, for treatment-naïve and patients with well controlled viral load.
Side effects include:
- Nausea
- Diarrhea
- Headache
- Creatine kinase (CK) elevation (sign of muscle damage)
- Myopathy and rhabdomyolysis (rare)
- Hypersensitivity reactions (rare)
- Depression and suicidal thoughts (rare)
Dolutegravir (Tivicay)
Available as tablets, for treatment-naïve patients and treatment-experienced patients with resistance to multiple antiretroviral drug classes.
Side effects include:
- Cholesterol and triglyceride elevation
- CK elevations
- Liver enzyme elevations
- Hyperglycemia (high blood sugar levels)
- Hypersensitivity reactions (rare)
- Depression and suicidal thoughts (rare)
The following are two more INSTIs which are currently available as a part of fixed dose, single pill combinations:
- Elvitegravir
- Bictegravir
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How Long Can You Live with HIV?
HIV stands for human immunodeficiency virus. If someone has HIV it means that they have been diagnosed with the HIV infection. AIDS (acquired immune deficiency syndrome); however, is the most advanced or final stage of the HIV infection. In the case of an untreated HIV infection, the overall mortality rate is more than 90%. The average time from infection to death is eight to ten years.
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Human Immunodeficiency Virus (HIV)
HIV (human immunodeficiency virus) infection left untreated causes AIDS (acquired immunodeficiency syndrome). The human immunodeficiency virus (HIV) is a type of virus called a retrovirus, which can infect humans when it comes in contact with tissues that line the vagina, anal area, mouth, or eyes, or through a break in the skin. HIV infection is generally a slowly progressive disease in which the virus is present throughout the body at all stages of the disease. Three stages of HIV infection have been described. The initial stage of infection (primary infection), which occurs within weeks of acquiring the virus, often is characterized by the flu- or mono-like illness that generally resolves within weeks. The stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) lasts an average of eight to 10 years without treatment. The stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed, is called the acquired immunodeficiency syndrome (AIDS). The symptoms are caused by the complications of AIDS, which include one or more unusual infections or cancers, severe loss of weight, and intellectual deterioration (called dementia). When HIV grows (that is, by reproducing itself), it acquires the ability to change (mutate) its own structure. These mutations enable the virus to become resistant to previously effective drug therapy. The goals of drug therapy are to prevent damage to the immune system by the HIV virus and to halt or delay the progress of the infection to symptomatic disease. Therapy for HIV includes combinations of drugs that decrease the growth of the virus to such an extent that the treatment prevents or markedly delays the development of viral resistance to the drugs. The best combination of drugs for HIV are those that effectively suppress viral replication in the blood and also are well tolerated and simple to take so that people can take the medications consistently without missing doses.
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How Long Does It Take to See Signs of HIV?
The signs and symptoms of HIV may first appear within two to four weeks of infection. The stage in which the symptoms appear is called the stage of acute HIV infection. The symptoms appear due to the resistance or fight of the immune system against HIV. Early diagnosis and treatment of HIV gets the best results.
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What Are the Four Stages of HIV?
The World Health Organization (WHO) classifies human immunodeficiency virus (HIV) into four stages. Stage 1 (HIV infection): The CD4+ cell count is at least 500 cells per microliter. Stage 2 (HIV infection): The CD4+ cell count is 350 to 499. Stage 3 (advanced HIV disease or AHD): The CD4+ cell count is 200 to 349. Stage 4 (Acquired immunodeficiency syndrome [AIDS]): The CD4+ cell count is less than 200.
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How Long Does It Take to Notice Signs of HIV?
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Human immunodeficiency virus (HIV) attacks the cells of the immune system, leading to AIDS and death if left untreated. The first signs of the human immunodeficiency virus infection are flu-like symptoms, which mainly start around two to four weeks after getting HIV. This stage is known as acute HIV infection.
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HIV stands for human immunodeficiency virus. If someone has HIV it means that they have been diagnosed with the HIV infection. AIDS (acquired immune deficiency syndrome); however, is the most advanced or final stage of the HIV infection. In the case of an untreated HIV infection, the overall mortality rate is more than 90%. The average time from infection to death is eight to ten years.How Long Does It Take to Notice Signs of HIV?
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HIV (human immunodeficiency virus) infection left untreated causes AIDS (acquired immunodeficiency syndrome). Still incurable, AIDS describes immune system collapse that opens the way for opportunistic infections and cancers to kill the patient. Early symptoms and signs of HIV infection include flu-like symptoms and fungal infections, but some people may not show any symptoms for years. Highly active antiretroviral therapy (ART) is the standard treatment for HIV infection. These combination drug regimens have made HIV much less deadly, but a cure or vaccine for the pandemic remains out of reach. HIV is usually transmitted through sexual contact or sharing IV drug needles, but can also infect someone through contact with infected blood. Sexual abstinence, safe sex practices, quitting IV drugs (or at least using clean needles), and proper safety equipment by clinicians and first responders can drastically reduce transmission rates for HIV/AIDS.What Are the Four Stages of HIV?
The World Health Organization (WHO) classifies human immunodeficiency virus (HIV) into four stages. Stage 1 (HIV infection): The CD4+ cell count is at least 500 cells per microliter. Stage 2 (HIV infection): The CD4+ cell count is 350 to 499. Stage 3 (advanced HIV disease or AHD): The CD4+ cell count is 200 to 349. Stage 4 (Acquired immunodeficiency syndrome [AIDS]): The CD4+ cell count is less than 200.What Is the Difference Between HIV-1 and HIV-2?
There are two main types of the human immunodeficiency virus (HIV), HIV-1 and HIV-2. HIV-1 is the most common type of HIV and accounts for 95% of all infections, whereas HIV-2 is relatively uncommon and less infectious. HIV-2 is mainly concentrated in West Africa, is less deadly and progresses more slowly.What Is Usually the First Sign of HIV?
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