How Does Antiretroviral Therapy Work
Antiretroviral therapy medication prevents the human immunodeficiency virus from multiplying, which reduces the viral load in the body. Having less HIV in the body allows the immune system to recover and produce more infection-fighting CD4 cells. Because the amount of HIV in the body is reduced, this also helps reduce the risk of HIV transmission.
There are several steps in the life cycle of HIV that form the basis for antiretroviral therapy.
Entry
HIV circulates in the bloodstream and binds to receptors on the surface of the CD4 immune cells, which leads to membrane fusion and internalization of the viral genetic material and enzymes necessary for replication of the virus.
Entry inhibitors include:
- Fusion inhibitor enfuvirtide
Reverse transcription
HIV uses reverse transcriptase to convert its genetic material into DNA, which results viral DNA migrating into the nucleus of the cell.
Nucleoside/nucleotide reverse transcriptase inhibitors include:
- Tenofovir disoproxil fumarate and tenofovir alafenamide
Recommended Initial Regimens In Certain Clinical Situations
Multiple antiretroviral regimens are available that are effective and tolerable, but are considered inferior to the regimens listed above. The Adult and Adolescent ARV Guidelines denotes this category as Recommended Initial Regimens in Certain Clinical Situations. This category also addresses regimens to consider when abacavir, tenofovir alafenamide, and tenofovir DF cannot be used or are not optimal to use, as well as addressing specific circumstances that apply to certain 2-drug regimens.
Getting Support With Starting Treatment
Its important that you feel ready to start ART and understand how to take it properly. Current HIV treatment has to be taken every day for the rest of your life. You might feel good about starting HIV treatment, because it is something you can do to stay healthy and strong. But it is also normal to feel worried about it, or to have questions.
In addition to talking to your doctor, you may find it helpful to talk to someone who has experience of taking HIV treatment. Many clinics have peer mentors, who can offer support and information, or can put you in touch with community organisations and peer support groups.
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Box 5 Recommendations For Laboratory Monitoringa
Abbreviation: ART, antiretroviral therapy.
a See text for essential details and cautions.
b The recommendation or the evidence rating has not changed substantially since the 2014 report.
If ART is being initiated on the first clinic visit, all laboratory specimens should be drawn prior to the first dose of ART resistance testing results should be used to modify the regimen as necessary . A similar process should be used for rapid ART initiation for acute or advanced HIV infection.
When Should I Start Antiretroviral Treatment
Its now recommended that people diagnosed with HIV start antiretroviral treatment straight away. This is because the sooner you start treatment, the sooner you can benefit from it. Starting treatment as soon as possible protects your immune system from damage and gives you the best chance of staying strong and healthy in the future.
I immediately started my treatment, and boy I have to tell you, I never experienced any sort of setback and have never been sick – and now I am even undetectable.
– Mpho, South Africa
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When To Start Hiv Treatment
Its now recommended that everyone diagnosed with HIV starts treatment straight away after being diagnosed.
In the UK, national guidelines set out standards for HIV treatment. They currently recommend that anyone with HIV who is ready to commit to treatment should start it regardless of their CD4 count .
What Is Hiv Treatment
HIV treatment involves taking medicines that slow the progression of the virus in your body. HIV is a type of virus called a retrovirus, and the combination of drugs used to treat it is called antiretroviral therapy . ART is recommended for all people living with HIV, regardless of how long theyve had the virus or how healthy they are. ART must be taken every day, exactly as your health care provider prescribes.
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Highly Active Antiretroviral Therapy
In 1996, highly active antiretroviral therapy was introduced for people with HIV and AIDS. HAART â often referred to as the anti-HIV “cocktail” â is a combination of three or more drugs, such as protease inhibitors and other anti-retroviral medications. The treatment is highly effective in slowing the rate at which the HIV virus replicates itself, which may slow the spread of HIV in the body. The goal of HAART is to reduce the amount of virus in your body, or the viral load, to a level that can no longer be detected with blood tests.
Hiv Integration And Integrase Strand Transfer Inhibitors
HIV Integrase
The HIV integrase enzyme is a 288 amino-acid protein that consists of three distinct structural domains: the amino -terminal domain, the catalytic core domain, and the carboxy -terminal domain the catalytic core domain contains a trio of amino acids that coordinate binding with a divalent metal cofactor and this region forms the active catalytic site .. The HIV integrase enzyme can exist in the form of a monomer, dimer, tetramer, and possibly higher order forms, such as octamers. Each HIV-1 virion has an estimated 40 to 100 integrase enzymes.
HIV Integration
Integrase Strand Transfer Inhibitors
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Box 3 Art And Opportunistic Infection Recommendationsa
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ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis .
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ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/µL or less and within the first 2 to 8 weeks for those with CD4 cell counts above 50/µL .
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Neither tenofovir alafenamide nor cobicistat-boosted elvitegravir is recommended with rifamycin drugs . A boosted protease inhibitorbased regimen should be used only if an integrase strand transfer inhibitor is not an option, and rifabutin, 150 mg/d, should be substituted for rifampin in the antituberculosis regimen .
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Primary Mycobacterium avium complex prophylaxis is not recommended if effective ART is initiated immediately and viral suppression achieved .
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Primary Pneumocystis pneumonia prophylaxis is recommended for patients who meet CD4 cell count criteria , even if taking ART.
Abbreviation: ART, antiretroviral therapy.
a See text for essential details and cautions.
b The recommendation or the evidence rating has not changed substantially since the 2014 report.
Recommendations For Initiation Of Antiretroviral Therapy
The Adult and Adolescent ARV Guidelines recommend initiation of antiretroviral therapy for all persons with HIV to reduce morbidity and mortality associated with HIV infection and to prevent HIV transmission to others . In addition, antiretroviral therapy should be started immediately, or as soon as possible, after the HIV diagnosis.
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How Should I Take My Antiretroviral Treatment
When and how you take your ART will vary depending on the specific antiretroviral drugs you take. Most antiretroviral drugs are taken once a day, with or without food. However, some drugs are taken twice a day. If this might be something you find difficult, talk to your doctor about your options.
Once you start ART its very important that you take it properly and dont miss or skip doses, as this can lead to something called HIV drug resistance, and may mean that your drugs dont work as well for you in the future. If youre finding it hard to take your treatment at the right times and in the right way, speak to your healthcare worker. They can offer you support and give you advice on how to make taking your treatment easier.
Hiv Protein Processing And Hiv Protease Inhibitors
HIV Protease
The HIV protease enzyme is a 99-amino-acid dimer made up of two identical subunits . This enzyme has a key role in post-transcriptional processing of the Gag and Gag-Pol polyproteins. The HIV protease has three major conformational forms: open, semi-open, and closed . The protease enzyme has an active site near the center of the heterodimer and the active site includes two opposed aspartic acid residues. Movement from the open to closed causes the flap ends to overlap and functionally act as a molecular scissor.
Polyprotein Processing and Maturation
Protease Inhibitors
The HIV protease inhibitors are structurally complex molecules that bind to the active site of HIV protease and inhibit the protease enzyme activity . The HIV protease inhibitors disrupt the normal Gag and Gag-Pol polyprotein processing, causing arrest of the normal maturation process, which thereby prevents infection of new cells. The protease inhibitors do not have an impact on cells already infected with HIV .
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What Is Antiretroviral Therapy For Hiv Infection
Antiretroviral therapy is a combination treatment regimen for HIV infection, with different classes of drugs that work in different ways. Each ART regimen is tailored to suit individual conditions and requirements. There is no cure for HIV infection, but ART can effectively manage HIV as a chronic disease.
Protease inhibitors have a low incidence of drug resistance in treatment-naive patients . Drug resistance tests are performed before ART is initiated, but protease inhibitor-based ART regimens are often started as first-line treatment for acute HIV infection while test results are awaited.
Combination Antiretroviral Therapy For Hiv Infection
Am Fam Physician. 1998 Jun 1 57:2789-2798.
The primary goal of antiretroviral therapy for human immunodeficiency virus infection is suppression of viral replication. Evidence indicates that the optimal way to achieve this goal is by initiating combination therapy with two or more antiretroviral agents. The agents now licensed in the United States for use in combination therapy include five nucleoside analog reverse transcriptase inhibitors , two nonnucleoside reverse transcriptase inhibitors and four protease inhibitors . Current recommendations suggest that antiretroviral therapy be considered in any patient with a viral load higher than 5,000 to 20,000 copies per mL, regardless of the CD4+ count. Selection of the combination regimen must take into account the patient’s prior history of antiretroviral use, the side effects of these agents and drugdrug interactions that occur among these agents and with other drugs as well. Because of the potential for viral resistance, nonnucleoside reverse transcriptase inhibitors and protease inhibitors should only be used in combination therapy. Antiretroviral agents are rapidly being developed and approved, so physicians must make increasingly complex treatment decisions about medications with which they may be unfamiliar.
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What Should People Know About Taking Hiv Medicines
Taking HIV medicines keeps people with HIV healthy and prevents HIV transmission. Taking HIV medicines every day and exactly as prescribed also reduces the risk of drug resistance.
But sometimes HIV medicines can cause side effects. Most side effects from HIV medicines are manageable, but a few can be serious. Overall, the benefits of HIV medicines far outweigh the risk of side effects. In addition, newer HIV medicines cause fewer side effects than medicines used in the past. As HIV treatment continues to improve, people are less likely to have side effects from their HIV medicines.
HIV medicines can interact with other HIV medicines in an HIV regimen or with other medicines a person is taking. Health care providers carefully consider potential drug interactions before recommending an HIV regimen.
Choosing The Anchor Drug In Regimen
The choice of the third drug, commonly referred to as the anchor drug, to combine with an NRTI backbone for an initial antiretroviral regimen depends on clinical, pharmacologic, and patient-level factors. In the Adult and Adolescent ARV Guidelines, the Recommended Initial Regimens for Most People with HIV utilize the INSTI bictegravir or dolutegravir as the anchor drug the recommendation to use these two INSTIs as the anchor drug is based on high efficacy, high genetic barrier to resistance, low adverse effect profile, and minimal drug interactions. In previous years, the Adult and Adolescent ARV Guidelines included the INSTI elvitegravir, raltegravir, protease inhibitors, and NNRTIs as the anchor drug in the recommended regimen category, but certain limitations, such as poor tolerability, restrictions for use based on CD4 cell count and/or HIV RNA level, and lower genetic barrier to resistance have relegated these anchor drugs to the alternative regimen category.
Choice of INSTI
Choice of PI
Choice of NNRTI
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What Are Protease Inhibitors In Antiretroviral Therapy For Hiv Infection
Protease inhibitors are one of the classes of drugs in the combination of drugs used for antiretroviral therapy for human immunodeficiency virus infection. Protease inhibitors were first introduced in 1995 and are effective for both HIV-1 and HIV-2 infections.
Nucleoside reverse transcriptase inhibitors form the backbone of the three-drug ART regimen, and protease inhibitors are often an additional drug class included in the regimen, to improve the chances of controlling the viral growth.
Hiv Drug Resistance And Covid
A continuous supply of antiretroviral drugs is essential to avoid treatment interruption and prevent the emergence and spread of HIV drug resistance. Limited access to health centres can result in treatment interruption among individuals on antiretroviral therapy. To mitigate the impact of the COVID-19 pandemic on HIV treatment access, countries are encouraged to:
- safely maintain access to essential health services, including the antiretroviral therapy programme and
- urgently adopt and implement WHO recommendation of multi-month dispensing for antiretroviral medicines, whereby medicines are dispensed for longer periods of time .
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Treatment Helps Prevent Transmission To Others
- If you have an undetectable viral load, you have effectively no risk of transmitting HIV to an HIV-negative partner through sex.
- Having an undetectable viral load may also help prevent transmission from injection drug use. We dont have data about whether having an undetectable viral load prevents transmission through sharing needles, syringes, or other injection equipment . It very likely reduces the risk, but we dont know by how much.
- Having an undetectable viral load also helps prevent transmission from mother to baby. If a mother with HIV takes HIV medicine as prescribed throughout pregnancy, labor, and delivery and gives HIV medicine to her baby for 4 to 6 weeks after birth, the risk of transmitting HIV to her baby can be 1% or less.
- Having an undetectable viral load reduces the risk of transmitting HIV to the baby through breastfeeding, but doesnt eliminate the risk. The current recommendation in the United States is that mothers with HIV should not breastfeed their babies.
New Antiretrovirals Improve Quality Of Life Of Hiv/aids Patients
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Today, about 35 million people live with human immunodeficiency virus infection globally.
There is currently no cure for HIV infection however, over the past few years the authorisation and availability of potent antiretroviral medicines has fundamentally changed treatment and management of HIV infection. These life-long treatments can effectively control the virus, enabling patients who have access to these medicines to lead full and active lives.
The European Medicines Agency plays a key role in the authorisation of medicines to treat HIV infection and acquired immunodeficiency syndrome . All antiretroviral medicines in the European Union have to be authorised centrally at European level, rather than separately in each EU Member State. This allows the rapid availability of these medicines to HIV patients across the EU. To date, 36 anti-HIV medicines have been centrally authorised in the EU.
The therapeutic options available for patients with HIV infection can effectively control the virus and the development of resistance has become less frequent. However, patients now need simplified and well tolerated treatments to facilitate the management of their disease throughout their lives, notes Marco Cavaleri, Head of EMA’s Anti-infectives and Vaccines Office.
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Box 7 Recommendations For Prevention Of Hiv Infectiona
Abbreviations: ART, antiretroviral therapy PrEP, preexposure prophylaxis TDF, tenofovir disoproxil fumarate.
a See text for essential details and cautions. All recommendations are new or evidence ratings have changed substantially since the 2014 report. Components separated with a slash indicate that they are available as coformulations.
What Is Antiretroviral Therapy
Antiretroviral therapy refers to combination drug therapy used to treat human immunodeficiency virus . Antiretroviral drug therapy frequently combines three or more drugs from more than one class to help prevent drug resistance.
Antiretroviral therapy does not cure HIV, but it helps patients live longer and also reduces the risk of transmitting the virus to others. People who are diagnosed with HIV should start taking HIV medications right away.
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Should You Ever Take A ‘holiday’ From The Drugs
Taking a “drug holiday” from your HIV treatments for reasons other than a severe reaction to medications may be harmful to your health. Having said that, your provider may suggest that you temporarily stop your antiretroviral drugs for certain specific reasons. Be sure to talk with your provider about this issue if you have questions about it. How you stop taking your HIV drugs safely can be a complicated process.
Remember, just skipping doses without your provider’s instruction is dangerous you should never change your treatment plan without talking with your provider.
How Do You Deal With Side Effects
Some side effects can be hard to deal with. One way to cope with them is to know what to watch out for and have a plan to deal with problems that come up.
That’s why you need to talk to your provider about the risk of side effects from different drugs, before you start therapy.
At the beginning of any treatment, you go through a period of adjustment–a time when your body has to get used to the new drugs you’re taking. Sometimes you’ll have headaches, an upset stomach, fatigue, or aches and pains. These side effects may go away after a few days or a few weeks.
If you notice any unusual or severe reactions after starting or changing a drug, report the side effects to your provider immediately.
More information is available in the Side Effects Guide.
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