Antiviral therapy for HIV drugs. Antiretroviral drugs. Something about changing medications

The treatment of HIV infection can sometimes be very difficult to understand, especially the differences, pros and cons of antiretroviral drugs.

In this article, a brief “summary” of each drug is offered by two specialists - “ doctor"practitioner Stephen Becker and " activist» Deneen Robinson is HIV positive.

Retrovir (zidovudine, AZT)

Doctor

The oldest and historically most commonly used antiretroviral drug, included in a wide variety of HAART combinations. Although not as strong and possibly more toxic than the newer generation of NRTIs, it remains a very important drug. Zidovudine has proven effective in preventing mother-to-child transmission of HIV and in occupational risk situations. However, due to new evidence of transmission of resistant virus, AZT is not always the best choice for people who have not previously taken HAART. Whether AZT will be included in future combination therapies can only be determined by further research.

Activist

AZT was created as an anti-cancer drug. In the 1980s, AZT was prescribed to people with HIV in huge doses, causing many side effects. As a result, the HIV-positive community has become very negative about taking it. However, the manufacturer has changed the formula of the drug and it is effective with little toxicity. AZT has proven to be effective as a base drug, as it works well with all other drugs except Zerit (d4T), AZT cannot be used with it. The company recommends that physicians closely monitor obese women and patients at risk for liver disease while taking AZT.

Videx (didanosine, ddI)

Doctor

ddI is another drug developed early in the epidemic, and like AZT, it has stood the test of time. The drug has average effectiveness and predictable toxicity. Peripheral neuropathy and pancreatitis are the most serious side effects possible. The drug is good for both patients taking therapy for the first time and those who have experience taking HAART.

Activist

The first thing you remember when talking about Videx is large chalky tablets with a rather vile taste. They are also harmful to tooth enamel. Thanks to Bristol-Myers - they started producing Videx EC in a casing. Diarrhea also does not occur with Videx EC, although some may still experience digestive upset. Videx should be taken on an empty stomach. Zerit and Videx should not be taken together as this increases the risk of peripheral neuropathy and pancreatitis. Remember that you should never take Videx with an antacid. Also, Videx should not be taken with AZT or Hivid due to the increased risk of peripheral neuropathy.

Hivid (zalcitabine, ddC)

Doctor

Rarely used and for good reason. Its toxicity, primarily the high risk of peripheral neuropathy, limits its use. There are better drugs for people at any stage of HIV infection.

Activist

One of the earliest nucleoside reverse transcriptase inhibitors. Today it practically does not occur, only in combinations for people with multiple resistance. Due to lack of clinical data and overlapping toxicity, not used with AZT. The main side effect is peripheral neuropathy, which occurs in every third patient taking the drug. The main means of combating neuropathy is to reduce the dose and change the drug.

Zerit (stavudine, d4T)

Doctor

d4T is as effective as AZT, the main problem with taking it is the side effects when taken long term. Peripheral neuropathy and high serum levels occur with moderate frequency in treatment-naïve patients taking d4T. Loss of fat on the face and limbs may be another side effect. All these effects are associated with disruption of the cell's mitochondrial functions responsible for energy production.

Activist

Zerit remains one of the most popular drugs in the treatment of HIV infection. The most severe side effects that can occur when taking d4T are peripheral neuropathy and pancreatitis. It is dangerous for pregnant women to take d4T together with Viramune and ddI. Directions for use of d4T warn that it is associated with an increased risk of lipoatrophy (loss of fat layer).

Epivir (lamivudine, 3TC)

Doctor

3TC belongs to the modern generation of NRTIs. Approximately 50% stronger than other drugs in this group. Very well tolerated, few side effects. The Achilles heel of 3TC is the low genetic barrier, meaning one single mutation can render the drug useless. Included in the first treatment regimen, both in combination with protease inhibitors and NNRTIs. As long as there are no resistant mutations, it is excellent, but even in the presence of mutations it may be useful and indicated for patients with multiple resistance.

Activist

One of the simplest NRTIs. 3TC is very popular due to its low number of side effects. However, people taking it need to remember that resistance to 3TC quickly develops. One possible side effect of 3TC is hair loss. 3TC has been successfully combined with AZT in one tablet - Combivir, and with AZT and Ziagen in Trizivir. Finally, 3TC is approved for the treatment of hepatitis B, so people with dual diagnoses can afford to "save money" by taking the pills.

Ziagen (abacavir, ABC)

Doctor

Abacavir, like 3TC, is a very strong drug. Unlike other drugs, it easily penetrates nerve cells. This is very important because HIV can penetrate the tissue of the central nervous system. ABC has a high genetic barrier, which means that resistance to it arises slowly. Resistance to ABC requires several mutations. It is usually well tolerated and has few side effects. Approximately 5% of patients have a hereditary predisposition to hypersensitivity to the drug. Hypersensitivity should not be confused with allergies; it is a special reaction associated with certain genes. Hypersensitivity occurs most often in whites and women. Given its effectiveness and tolerability, ABC will be useful for many patients in their first treatment regimen or when resistance to other drugs has developed.

Activist

This medicine has a large stone in the sinus - a hypersensitivity reaction. It interferes with further use of the drug. The reaction most often occurs in the first eleven days. In rare cases, hypersensitivity may appear even after 8 months. Always carry a list of hypersensitivity reaction symptoms with you. When the first signs of hypersensitivity appear, stop taking the drug. Continued use of the drug during a reaction can be fatal. In this case, you should never take abacavir in the future. Ziagen was originally developed as an alternative to NNRTIs and protease inhibitors, but studies have shown that it is inferior to them in effectiveness.

Rescriptor (delavirdine, DLV)

Doctor

Delavirdine is an NNRTI, but is used very rarely. Less effective than Viramune or Stokrin. However, it is less likely to cause rash and hepatotoxicity. Unless further research shows additional benefits, it is unlikely to replace Viramune and Stokrin, which have been much better studied.

Activist

The oldest and least used non-necleoside. After all these years, the true effectiveness of the drug can only be discovered in the future. It is currently being tested for its use in combination with nelfinaviram. However, rather than studying its effects with protease inhibitors, perhaps it should be released in a new dosage to give people another drug to choose from.

Viramune (nevirapine, NVP)

Doctor

Nevirapine is a very strong drug that penetrates well into the cells of the nervous system. Like other drugs of the class, it has a low genetic barrier; resistance to it quickly develops. Quite toxic, incompatible with many drugs (including those not related to HIV). Has the same effectiveness as efavirenz (Stokrin). Rash as a side effect occurs in every third patient taking Viramune. In rare cases, this rash can become severe. Hepatotoxicity (toxic effect on the liver) is observed in 8-15% of patients taking Viramune, usually manifesting itself at 6-12 weeks of therapy. Cases of fatal hepatotoxicity have been reported. Not recommended for people with chronic hepatitis and other liver diseases. Effective for preventing HIV from mother to child. For unknown reasons, it may have a beneficial effect on blood cholesterol levels.

Activist

As effective as Stokrin. Since its cost is lower, this makes it a good alternative. The success of nevirapine in preventing mother-to-child transmission of HIV has contributed to its spread throughout the world. However, it also has its problems. In addition to the potentially dangerous rash characteristic of NNRTIs, it has its own black box - high liver toxicity. May cause toxic hepatitis. According to some data, the rash is more common in people with hypersensitivity to sulfonamides.

Stocrin (ifavirenz, EFV)

Doctor

Ifavirenz is a very strong drug, like nevirapine, it easily penetrates the central nervous system. Like other drugs of its class, it has a low genetic barrier, resistance occurs quite easily. Due to penetration into nerve cells, it may cause side effects related to mood and feelings. Approximately 50% of patients experience these side effects to varying degrees, but for the most part they are mild and go away on their own over time. Rash and hepatotoxicity are less common than with nevirapine. Contraindicated during pregnancy. Recommended in combination with d4T and 3TC.

Activist

Stocrin is a powerful medicine and if you can take it, it works. One of the best drugs for those who are starting therapy for the first time. Although prescribed more often than other drugs, it can cause quite serious side effects in the central nervous system. Everyone needs to be aware of these side effects and exercise caution. People with drug use, psychiatric illnesses, and suicide attempts need to be especially careful.

Invirase (saquinavir, SQV)

Doctor

Saquinavir was the first protease inhibitor, proposed in 1995. Best used in combination with ritonavir. The combination of saquinavir and ritonavir can be taken twice or even once daily. Usually the drug is tolerated quite well. Blood levels of the drug are higher in women, and side effects may be more common in women.

Activist

The first protease inhibitor to treat HIV. Large hard gel capsules that are quite difficult to digest. As a result, it is recommended in combination with ritonavir. Only in combination does it achieve its effectiveness.

Crixivan (indinavir)

Doctor

Indinavir has become less and less used since newer drugs became available. The main reason is long-term toxicity. Indinavir is taken three times a day on an empty stomach. May be taken twice daily with ritonavir. Unfortunately, when combined with another protease inhibitor, the side effects become even greater. Despite its very high effectiveness, it is less desirable than other drugs that have less toxicity.

Activist

Although saquinavir was the first protease inhibitor, it was Crixivan that revolutionized the treatment of HIV infection. There was a time when Krixivan was called "healing". He gave us all hope, an undetectable viral load and a lipodystrophy belly. Should be taken three times a day, as it is quickly eliminated from the body. Krix can now be taken with ritonavir twice daily. Along with it, you will have to drink a lot of water to prevent the formation of kidney stones. The main drawback is the number one side effect associated with protease inhibitors - lipodystrophy, diabetes and high blood lipids. Taking the drug three times a day, observing food and water restrictions - this requires a lot of discipline. If you are a busy person in life, ask your doctor about other drugs or a combination version. Too many missed doses and you will develop resistance, not only to Crixivan, but also to other protease inhibitors.

Norvir (ritonavir)

Doctor

Ritonavir is now used not as a stand-alone drug, but to “boost” other protease inhibitors. Alone, it is characterized by high toxicity; in combination with other protease inhibitors, it is usually well tolerated.

Activist

Norvir is a very strong protease inhibitor. However, the characteristic disgusting taste, numbness of the tongue and other side effects make it undesirable to take. The best use of Norvir is in combination with other protease inhibitors. In this case, there are fewer side effects.

Viracept (nelfinavir)

Doctor

Nelfinavir was once the most popular protease inhibitor. Lost popularity despite slowly emerging resistance. The effectiveness of nelfinavir is highly dependent on taking it on a full stomach. In addition, the food should contain a lot of fat, which helps nelfinavir to be absorbed. Thus, it can only be taken with fatty, high-calorie foods. Also, its use is limited by frequent diarrhea, increased levels of cholesterol and tricyclides in the blood. May be taken during pregnancy.

Activist

Diarrhea has been a curse ever since the drug hit the market. It is advisable to prescribe it along with prescriptions and anti-diarrhea medications. You can reduce this side effect if you change your diet correctly. A possible side effect that is not listed in the instructions is weight gain. It is difficult to maintain a slim figure by eating 50 grams of fat with food and nelfinavir three times a day (according to the manufacturers, this is necessary for the absorption of the drug). Despite all this, it is a very strong drug. Effective for both “newbies” and “experienced” people taking HAART. Resistance to it is determined by a unique mutation. This means that if you develop resistance to Viracept, you can still take other protease inhibitors.

Fortovase (saquinavir)

Doctor

Saquinavir was the first protease inhibitor, approved in 1995. Originally produced in hard gel capsules, it was later replaced by soft gel capsules, which improved its absorption. A new form of the drug, Fortovase, is more effective, but causes more gastrointestinal side effects. Cholesterol and tricyclide levels increase slightly when taking Fortovase; in general, the drug is well tolerated.

Activist

A remake of Invirase - Fortovase, is absorbed better. Food helps the drug absorption process. Unfortunately, you need to take it three times a day. Research shows that with ritonavir, Fortovase can be taken twice daily. So far, the drug has been harmed by the “bad reputation” of its predecessor Invirase, which is why it has not found widespread use.

Agenerase (amprenavir)

Doctor

Suitable for both beginners in therapy for the first time and for those who have experience with HAART. Shown to be effective for people with low immune status and high viral load. Can be effective together with Kaletra.

Activist

If you take Agenerase, then first of all it is sixteen tablets a day, which is not at all small, and this does not count tablets of other drugs. It has become more popular due to its “enhancement” with Norvir, which reduces the number of tablets. Agenirase can also be taken in solution, which, however, is more toxic for women. Do not take with echinacea (medicines to “boost immunity”), St. John’s wort (“natural” antidepressants), vitamin E, garlic and milk thistle.

Kaletra (lopinavir and ritonavir)

Doctor

Kaletra, approved in 2000, has become the gold standard for treating HIV infection. The only combination drug with ritonavir has excellent efficacy, rapid reduction of viral load, low level of resistance development. Refers to "preferred modes". Associated with increased levels of cholesterol and tricyclides in the blood - in approximately 30−35% of patients. These metabolic changes are sometimes severe and may lead to the need to discontinue the drug. As with other protease inhibitors, it is necessary to monitor blood glucose levels - there may be a tendency to diabetes. Kaletra can be used with other protease inhibitors, especially for patients with multidrug resistance.

Activist

At first I thought this drug was a stupid idea - combining two drugs that need to “strengthen” each other. However, this idea reduced the number of pills taken and side effects. Recommended for patients starting HAART for the first time. People prone to diabetes, cardiovascular disease and obesity should be prescribed the drug with caution, as well as other protease inhibitors. Check your blood glucose, cholesterol, and tricyclide levels regularly while taking Kaletra. The manufacturing company even decided to conduct a clinical trial in which people starting taking Kaletra would simultaneously start taking statins to normalize cholesterol levels in the blood.

Positively Aware, January/February 2004

Indications for starting ART include:

the presence of clinical symptoms of secondary diseases, which indicates the presence of immunodeficiency;

decrease in the number of CD4 lymphocytes in the blood;

the presence of active HIV replication, assessed by the level of HIV RNA in the blood plasma.

In the absence of clinical symptoms of secondary diseases, the main criterion for starting ART in patients with chronic HIV infection is the number of CD4 lymphocytes. Almost all experts are unanimous in the opinion that if the CD4 lymphocyte count is less than 200/μl, treatment should be started immediately.

Almost all recommendations specifically emphasize that the patient must be ready to begin treatment, understand its goals and be committed to therapy, i.e. take medications prescribed by the doctor in the specified dosage, at certain time intervals, and in accordance with the recommendations for use food, liquids and other medications and dietary supplements (possible drug interactions). Treatment is prescribed only after the patient has signed a voluntary informed consent form.

In addition to the presence of clinical symptoms of secondary diseases, a decrease in the number of CD4 lymphocytes less than 350/ml, the criterion for prescription of ART is a high level of viral load (HIV RNA more than 100,000 copies/ml).

Particular difficulties arise for a doctor when deciding whether to prescribe ART to a patient who has been diagnosed with acute HIV infection. Currently, there is no consensus among specialists on the advisability of using ART in the acute period of HIV infection.

In accordance with Russian recommendations, treatment for patients in the acute period of HIV infection is indicated if the patient has a decrease in the number of CD4 lymphocytes to less than 1200/ml (stages 2A and 2B) or stage 2B of HIV infection has been established (acute HIV infection with secondary diseases) and at the same time the number of CD4 lymphocytes is reduced to less than 350/μl. The duration of antiretroviral therapy in patients with acute HIV infection usually ranges from 6 to 12 months.

First line ART schemes

The basal regimen is the regimen prescribed to most patients. Alternative regimens include ART regimens used for special categories of patients due to the impossibility of prescribing them a basic regimen due to contraindications. First-line ART regimens refer to those prescribed to patients who have not previously received ARVs. Second-line regimens refer to ART regimens used in case of ineffectiveness of the first-line therapeutic regimen.

Most existing recommendations suggest that the preferred first-line ART regimen include 2 drugs from the group of HIV nucleoside reverse transcriptase inhibitors (NRTIs) and 1 boosted HIV protease inhibitor (PI) or non-nucleoside HIV reverse transcriptase inhibitor (NNRTI - efavirenz or nevirapine). Regarding the combination of NRTIs, almost all experts advise the use of combination drugs that include 2 NRTIs. Currently, doctors have 3 drugs in their arsenal, each containing 2 NRTIs: Combivir (zidovudine + lamivudine), Kivexa (lamivudine + abacavir) and Truvada (tenofovir + emtricitabine).

The advantages of these combination drugs include taking 1 capsule once a day, regardless of food intake, and no effect on hematopoiesis. The most significant adverse effect when using Kivexa is the development of a delayed-type hypersensitivity reaction (DHT) to abacavir.

Taking into account the above data, the optimal choice of the initial combination of two NRTIs in Russia is the drug Combivir (zidovudine + lamivudine), which is prescribed 1 tablet 2 times a day. If anemia or neutropenia is present, phosphazide or stavudine in combination with lamivudine can be used instead of zidovudine.

When using other combinations of drugs from the NRTI group, the presence of drug interactions between drugs should be taken into account:

When taking didanosine and stavudine simultaneously, the risk of developing lactic acidosis increases significantly. The combination of these drugs is contraindicated in pregnant women;

If a patient has polyneuropathy, the combination of didanosine and abacavir leads to a significant increase in it;

When tenofovir and didanosine are combined, the concentration in the blood of the latter increases significantly, which leads to an increased risk of developing pancreatitis and peripheral polyneuropathy. In addition, this combination of drugs leads to a weak immunological response to ART;

Combinations of the drugs zidovudine (or phosphazide) + stavudine and lamivudine + emtricitabine should not be used, since these drugs are analogues of the nucleosides thymidine and cytidine, respectively. When these drugs are taken simultaneously, the effectiveness of treatment decreases because they compete with each other for intracellular enzymes that carry out the process of drug phosphorylation.

As a third drug in the ART regimen, experts suggest including either a drug from the NNRTI group or a PI boosted with ritonavir. Among drugs from the NNRTI group, it is recommended to include nevirapine or efavirenz in the first-line ART regimen, with preference given to efavirenz. A significant limitation in the use of nevirapine is the high content of CD4 lymphocytes (more than 250/ml in women and 400 in men), which significantly increases the incidence of severe hepatotoxicity. Efavirenz is not recommended for pregnant women and women planning pregnancy due to the increased likelihood of developing fetal pathology (especially when using the drug in the first trimester of pregnancy).

ART regimens differ in their safety profile, i.e. frequency and severity of certain adverse events. It is this indicator that can be decisive when drawing up a therapeutic regimen for a particular patient. In addition, the convenience of taking the drugs, the presence of concomitant diseases or conditions, as well as possible drug interactions between ARVs and the drugs the patient is taking are also taken into account. From the point of view of the optimal combination of effectiveness and ease of administration, an ART regimen that includes the drugs tenofovir, emtricitabine and efavirenz has a certain advantage. The combined drug Atripla contains all these three drugs in 1 tablet, which the patient takes once a day, regardless of food and liquid intake.

In Russian recommendations, one of the main criteria for choosing the preferred first-line ART regimen is the cost of the ART regimen. When choosing a basic first-line ART regimen, Russian specialists took into account, in addition to cost, effectiveness, safety, tolerability, ease of administration, as well as the presence of this regimen in foreign recommendations. In accordance with Russian recommendations, the preferred ART regimen is a regimen that includes the drugs Combivir (zidovudine + lamivudine) and efavirenz (2 NRTIs + NNRTIs). The patient needs to take 1 tablet in the morning and 2 tablets in the evening, and the cost of such an ART regimen, within the framework of the National Project, is less than 1800 US dollars per year.

Despite the progress of modern medicine in the treatment and prevention of HIV infection, WHO estimates that at the end of 2012 there were 35.3 million people living with HIV in the world, of which 2.3 million were new infections. In addition, more than 1 million people die each year from HIV-related complications (1). HIV is spreading most rapidly in Eastern Europe, and the incidence in Ukraine remains at a fairly high level. That is why the main goal of WHO is to optimize the prevention of transmission of this disease and existing methods of therapy, as well as to ensure timely monitoring of the effectiveness of therapy, minimizing side effects and thus increasing the overall effectiveness of treatment (1).

How does HIV work?

HIV affects immunocompetent cells - CD4+ T-lymphocytes, also called “helpers” (from the English word “help” - to help). It is this population of lymphocytes, carrying CD4 receptors on the surface, that is responsible at the cellular level for the immune response - the body’s ability effectively resist infections. The virus gradually infects more and more CD4+ T-lymphocytes, and HIV-infected cells die. Accordingly, the number of CD4+ T-lymphocytes in the body decreases, which first leads to disruption of cellular immunity, and then of the humoral immune response ( production of antibodies that bind foreign agents when they enter the body). The virus then infects other types of cells, for example, macrophages, which are responsible for “neutralizing” foreign agents entering the body. As a result, the connection between different types of cells that underlies the immune system is disrupted. response. Damage to the immune system increases, which leads to infection of the patient with concomitant HIV (so-called opportunistic) infections - tuberculosis, toxoplasmosis, hepatitis B and other dangerous diseases. At later stages, damage to the immune system leads to the development of malignant neoplasms and acquired immunodeficiency syndrome (AIDS), the final stage of the disease. If left untreated, most HIV-infected people take approximately 10-15 years from the time they are diagnosed with HIV to the development of AIDS (3).

Can HIV be cured?

The main difficulty in the fight against HIV lies in the strong variability of the proteins that make up the virus shell, due to which the immune system is unable to produce antibodies that can block the virus as it exits the cell and prevent its further spread and death of the T-lymphocyte population. Therefore, today there is no medicine that can completely cure the disease, although the achievements of modern medicine allow us to hope that the world is on the verge of discovering a method of therapy that will ensure a complete recovery of the patient. In 2013, in the American state of Mississippi, a unique case of a 2.5-year-old girl was officially registered, who managed to recover immediately after an aggressive course of treatment carried out shortly after birth. And scientists at the University of Oregon managed to achieve success in researching an HIV vaccine on animals - if in the 1st phase of the study the drug helped only 50% of infected monkeys, then in the 2nd phase almost 100% of the animals completely got rid of the virus. This suggests that in the future there may be a way to neutralize the virus at the stage when it is still in the cell.

However, today, when there is no cure for HIV, the key factor on which the prognosis of the disease depends is the timely initiation of antiretroviral therapy, which can almost completely stop the progression of the disease and prevent further transmission of the virus (1).

What is antiretroviral therapy (ART)?

Antiretroviral drugs are aimed at slowing down the reproduction of the virus, i.e. to reduce its amount in the body. Antiretroviral therapy (ART) significantly slows the progression of the disease precisely by preventing viral replication and therefore reducing the concentration of viral RNA (known as the “viral load” or “viremia”) in the patient’s blood. At the end of 2012, 9.7 million people in low- and middle-income countries were receiving antiretroviral therapy. According to WHO recommendations, it is used only after all the necessary tests and the time of its start is determined individually by the attending physician (1). Indications for antiretroviral therapy and assessment of its effectiveness are based on regular determination of viral RNA concentrations (HIV RNA quantitation) and CD4 lymphocyte levels. A decrease in the concentration of viral RNA in the blood leads to an increase in the level of CD4 lymphocytes and a delay in the development of AIDS.

When should you start ART?

Regardless of disease stage, ART should be initiated in all patients with CD4 cell counts >350 cells/mm 3 and ≤ 500 cells/mm 3 . ART should also be initiated in all patients with a CD4 count ≤350 cells/mm3 in advanced and end-stage disease (WHO stages 3 and 4). If the patient has a concomitant infection, such as active tuberculosis or hepatitis B with chronic liver failure, ART is prescribed regardless of the CD4(2) count.

What drugs are prescribed as part of ART?

Highly active antiretroviral therapy, according to the 2013 WHO recommendations, consists of the simultaneous administration of three to four potent drugs. There are three groups of antiretroviral drugs: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs)(2).

According to WHO recommendations, two NRTIs and one NNRTI (tenofovir (TDF) + lamivudine (3TC) or emtricitabine (FTC) + efavirenz (EFV) in fixed doses are prescribed as the first line of ART for HIV infection; if this combination is intolerant, due to its unavailability on the market or its contraindications, zidovudine (AZT) + 3TC + EFV, or AZT + 3TC + nevirapine (NVP), or TDF + 3TC (or FTC) + NVP is prescribed. The use of stavudine (d4T) as first-line therapy is not recommended due to its serious side effects. A combination of two NRTIs and a ritonavir-boosted PI is recommended as second-line therapy. The general principles for switching to second-line therapy, as in the case of first-line therapy, are based on a combination of two NRTIs in fixed doses: if the regimen is TDF. + 3TC (or FTC) is ineffective, a regimen based on zidovudine and lamivudine (AZT + 3TC) should be used, and if this regimen, or a regimen based on stavudine, when used as first-line therapy, is ineffective, then vice versa , it should be replaced with a TDF + 3TC (or FTC) regimen. Of the protease inhibitors, atazanavir (ATV) and lopanavir (LPV) in fixed doses are recommended. Finally, WHO recommends that third-line treatment regimens be regulated by national protocols, including drugs with minimal risk of cross-resistance (resistance) of the virus to those drugs that have already been used in first- and second-line treatment regimens in these patients, if for some reason these the regimen had to be canceled (due to poor tolerability, ineffectiveness, and severity of side effects).

The effectiveness of therapy is determined through clinical studies 6-12 months after its initiation. The most reliable test is to measure the level of viral RNA in the blood (viral load), but if this test is not available, a simple measurement of the CD4 count is used, which can be used to judge the progress of the disease and the effectiveness of the regimen used (2).

Why is ART adherence critical to a patient's prognosis?

According to various sources, up to 50% of HIV carriers refuse therapy after two to three years of treatment, thereby dooming themselves to rapid progression of the disease and deterioration in quality of life (4). It is important to understand that HIV treatment is lifelong and cannot be stopped - otherwise the resumption of the life cycle of the virus, which will “raise its head” soon after stopping therapy, will lead to the beginning of a new round of death of immunocompetent cells, deterioration of the immune system, the addition of new infections and the progression of the disease up to development of AIDS. In fact, HIV therapy does not require any special changes in the patient’s usual regimen - ART drugs are usually taken once or twice a day, and patients who have the right treatment regimen adjust their regimen very quickly. It is no different from the drug regimens taken by the “healthy” part of the population - people with diabetes, thyroid diseases, cardiovascular diseases, and sometimes it turns out to be much simpler - it’s not for nothing that patients with a long history of taking ART often say that They take these tablets like vitamins.

Do not skip taking pills or “forget” about the next dose for more than 2 hours after the standard dosing time - statistics show that ART is effective when the patient takes at least 95% of the required dose of all drugs (4), which means that when If you take it once a day per month, you can skip just one dose, and if you take it twice a day, you can skip no more than 3 doses!

In addition, it is necessary to remember about possible drug interactions of ART components with other medications taken by the patient. Sometimes the latter can enhance the effect of ART, and sometimes, on the contrary, reduce it. The effect of drug interactions depends on the pharmacokinetics of additional drugs taken by the patient - the rate of reaching maximum concentration in the blood, half-life, absorption in the intestine. Therefore, you should not start taking any additional medications while on ART without consulting an infectious disease specialist. Even when taking painkillers or herbal remedies (herbal medicine), you should first consult a doctor. PIs and NRTIs are especially likely to interact with other drugs. Their effect may be weakened by drugs taken to reduce stomach acid (for example, proton pump inhibitors) or certain antibiotics (macrolides). Conversely, regular grapefruit juice can multiply the effectiveness of some ITs (4). There is also a “reverse” effect - drugs used for ART can reduce the effectiveness, for example, of some hormonal drugs, contraceptives - the latter are very quickly eliminated from the body under the influence of ART - therefore women taking ART are recommended to use additional methods of contraception. Some strong opioid painkillers (methadone) also interact with ART medications, which may require increased doses.

Separately, it should be noted drugs that lower the level of cholesterol (C) in the blood (statins), which some patients take constantly. Considering that one of the side effects of ART is an increase in the level of cholesterol, as well as other components of the so-called. "lipid profile" (for example, triglycerides (TG), it is logical to assume that against the background of ART, continued use of statins favors the general health of the patient by reducing cholesterol levels. However, since both statins and ART drugs are metabolized in the body in the same way, their simultaneous use increases the dangerous side effect of statins - muscle destruction, or rhabdomyolysis. Therefore, if you are taking statins and ART drugs at the same time, you should definitely consult your doctor.

When taking ART drugs, you should not believe the common myth that constant use of HIV pills is harmful and associated with irreversible toxic effects. HIV therapy does have side effects, which, however, can be minimized, and often reduced to zero, if you follow treatment recommendations and undergo the necessary examinations so that the doctor can figure out in time which organs and systems of the patient are most sensitive to the prescribed drugs, and relieve existing unwanted symptoms.

What side effects does ART have?

Side effects of ART are divided into so-called. “early” and “late” (4). “Early” effects include diarrhea, nausea, vomiting, thirst, abdominal pain, fatigue, insomnia, hair loss, and dyspepsia. Sometimes changes in the hematopoietic system can also be observed, determined by simple tests, for example, a general blood test (decreased number of neutrophils, or neutropenia) or biochemical studies (increased levels of ALT, AST (“liver tests”). It should be remembered that all these side effects the phenomena may be short-term, and also the fact that their occurrence is associated not with ART in general, but with taking a specific drug of a certain group (NRTI, PI).

“Late” effects of ART include those adverse events that may occur after many months or years of taking the drug. The most serious of them include disorders of carbohydrate metabolism (increased blood sugar levels, up to the development of diabetes) and changes in lipid (fat) metabolism. It is very important to diagnose these changes in a timely manner, since, unlike “early” effects, they can go unnoticed by the patient and, if untreated, increase the risk of cardiovascular diseases, even heart attack.

Modern medicine has all the means to prevent the development of “late” side effects of ART. The most notable of these is lipodystrophy, or the depletion of adipose tissue during ART, which is associated with lipid disorders and changes in the lipid profile of patients (5). Data from large studies indicate that the presence of lipodystrophy and increased CD4+ T-lymphocyte levels in patients with HIV are strongly correlated with an increased risk of cardiovascular events (heart attack) (5). In addition, lipodystrophy is very often associated with lipid metabolism disorders - an increase in cholesterol levels due to an increase in the level of low-density lipoproteins (LDL) and TG. An increase in cholesterol and triglyceride levels is especially common in patients receiving PI therapy enhanced with ritonavir. Therefore, one of the main recommendations for patients receiving PIs is regular monitoring of lipid metabolism parameters (lipidogram). 8-12 hours before this test, for which blood is taken from a vein on an empty stomach, the patient should not eat anything fatty, or better yet, not eat at all, in order to get accurate results (4). The accuracy of lipid profile results in patients with HIV is of paramount importance, since lipid disorders are important to diagnose at a stage before ART drugs lead to significant disorders. In the initial stages, lifestyle changes and adherence to a diet recommended for reducing cholesterol levels (anti-atherosclerotic diet), as well as moderate physical activity, are often effective. However, if these measures are ineffective, the patient may be prescribed drugs that reduce the level of cholesterol and TG in the blood - statins. As already mentioned, some of them interact with the components of ART, so the prescription of a cardiologist should be coordinated with the treating infectious disease specialist.

Finally, such an undesirable late effect of ART drugs as an increase in blood sugar levels can be easily stopped in the initial stages, while only fasting glucose levels are elevated - with the help of diet and lifestyle changes. It is much more difficult to do this later, when carbohydrate metabolism disorders increase and the patient even develops type 2 diabetes.

That is why for patients receiving ART therapy, regular monitoring of carbohydrate (fasting blood sugar) and lipid levels (level of total cholesterol and triglycerides, and, if necessary, a more extensive study, the so-called lipid profile) is of paramount importance (4) . In some regions (eg, on the African continent), such tests are recommended as routine screening for all patients with HIV infection, as an effective means of reducing the risk of CVD(6).

Can ART therapy ensure patients' quality of life?

Although ART therapy currently does not provide complete cure for the patient, it can significantly increase life expectancy without compromising the quality of life (4). It is very important to promptly, after confirming the diagnosis, begin one of the WHO-recommended treatment regimens and carefully adhere to it, informing the attending physician about all side effects, how you feel during therapy, additional medications taken, and also undergo prescribed examinations. Regular measurements of the level of viral load and/or CD4+ lymphocytes allow us to draw conclusions about the effectiveness of treatment, and regular monitoring of carbohydrate (blood sugar) and lipid (cholesterol, TG) metabolism will allow timely prevention of unwanted side effects of ART therapy on the body. With the correct selection of ART therapy, compliance with the doctor’s recommendations and regular follow-up examinations, it guarantees the patient a long and fulfilling life, in no way inferior in quality to the life of a healthy patient.

References:

World Health Organization (WHO). HIV/AIDS. Newsletter No. 360. October 2013.
World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva: World Health Organization; 2013.
Washington University Therapeutic Handbook. Moscow, 200.с 388-404.
Elżbieta Bąkowska, Dorota Rogowska-Szadkowska. LECZENIE ANTYRETROWIRUSOWE (ARV) . Materiały informacyjne dla osób żyjących z HIV. Krajowe Centrum ds.AIDS, Polska, 2007.
De Socio GV et al. CISAI study group. Identifying HIV patients with an unfavorable cardiovascular risk profile in the clinical practice: results from the SIMONE study. J Infect. 2008 Jul;57(1):33-40.
Ssinabulya I et al. Subclinical atherosclerosis among HIV-infected adults attending HIV/AIDS care at two large outpatient HIV clinics in Uganda. PLoS One. 2014 Feb 28;9(2)

Currently, antiretroviral therapy is helping millions of people around the world live lives without restrictions, despite the most terrible disease. It has not yet been possible to completely defeat the virus, but the ability to live up to 70 years as a carrier of the immunodeficiency virus is already a big victory.

They have been working since the very first recorded case of the disease, but only several decades later it was possible to find a successful approach to controlling the disease. Today, an infected person can live a long and full life, have healthy children, not be afraid of seasonal infections and work in almost any field.

How does antiretroviral therapy work?

Let's figure out how antiretroviral therapy works? This is not a magic pill, but a routine that the patient must strictly adhere to under the supervision of doctors. The complex of antiviral drugs is selected individually and is usually adjusted throughout the course of the disease.

Highly active antiretroviral therapy aimed at reducing the viral load and reducing the manifestations of the disease. Correctly selected treatment improves the quality of life, reduces the likelihood of the occurrence and development of opportunistic infections. Regular use of the drugs significantly prolongs the life of the infected person, gives a chance to delay the onset of the terminal stage of the disease, and also makes the carrier safe for sexual partners and the embryo of a pregnant infected woman.

Benefits of ART for HIV

The advantages of ART for HIV are obvious: the patient can live exactly the same as HIV-negative people. Of course, for maximum effect you need to give up bad habits and eat a healthy diet. Despite the possibility of side effects, taking medications is still the only option for active longevity.

ART HIV infected people should be prescribed by a doctor after a detailed examination. In recent years, views and approaches to fighting have changed, so it is strongly recommended to contact good doctors who follow the development of medicine.

ART side effects has, but correction during treatment, as well as additional medications, can reduce unpleasant manifestations to a minimum. Antiviral drugs can have toxic effects on the liver and kidneys, and in some cases on other organs. During treatment, nausea, diarrhea, and anemia may periodically occur. But a healthy diet and additional protective medications will help keep all parameters normal. According to statistics, approximately 80% of patients experience discomfort from side effects.

When is antiretroviral therapy prescribed?

As already mentioned, the approach to treatment has changed in recent years. Previously, treatment was prescribed immediately after the virus was detected, but now doctors have concluded that this was a mistake.

When is antiretroviral therapy prescribed? Only after the doctor has established the stage of the disease will he assess the condition of the patient’s body. Too early measures can lead to rapid mutation of the virus and a decrease in the effectiveness of the active substance.

Antiviral therapy for HIV prescribed for certain indicators:

T-lymphocytes 350 cells/ml and below;
Clinical stage of HIV is stage 3 or 4.

Simultaneously with the prescription of HAART, the patient is given a number of recommendations for maintaining health. This could be sports, diet, or a special daily routine. Recommendations are given individually, based on measuring the patient’s vital signs. Failure to comply with recommendations reduces the effectiveness of treatment and accelerates the development of the disease.

ARV treatment regimens

ARV therapy for HIV assigned in accordance with a specific scheme. The program is selected only by a qualified medical professional; there should be no self-medication. Conventionally, schemes are divided into 3 types:

First-line regimens – for those who have not previously taken ART;
Second-line regimens – for correction of therapy after first-line drugs;
Third-line regimens are for treatment in late severe stages, the so-called “rescue regimens.”

A change in the course of treatment occurs only by the decision of the attending physician. You should know that any successfully selected complex will give temporary success, because the virus adapts and develops resistance. For this reason, it is important to be observed regularly, monitor the condition and make timely corrections in the treatment program. Over time, some time after the start of the course, the level of T-lymphocytes begins to fall again, and the viral load begins to increase. This means that the virus has mutated and adapted, and it’s time to change the dosage or the drug itself.

Antiretroviral therapy in the treatment of HIV infected people

Antiretroviral therapy for HIV gives amazing results. The drugs are becoming more and more improved, which is also due to the constant mutation of the virus, which adapts. But still, each new generation of drugs is better than the previous one. The effectiveness of treatment is different for everyone, this is due to the individual characteristics of the body. But, nevertheless, for almost every infected person it is possible to select an effective combination of substances.

Retroviral therapy for HIV usually includes 3 or 4 drugs, plus hepatoprotective or other supporting complexes are additionally prescribed to improve well-being. You can evaluate the first results and adjust treatment 6-8 months after the start.

Antiretroviral therapy for HIV infected people treatment is strictly under supervision and control; you cannot ignore the requirements to take tests or come for an examination.

Do not forget that treatment cannot be stopped, even if remission has been achieved and the indicators have returned to normal, as in uninfected people. The virus cannot yet be eliminated 100% from the body, so taking medications is mandatory for the rest of your life. HAART is a mandatory measure in treatment; other tablets, except antiviral ones, only help maintain the body’s strength, but do not affect the course of the disease in any way.

Possible contraindications of ART for HIV and side effects

What is the difficulty of taking antiretroviral therapy?, so it is in the side effects that can cause significant discomfort. Any ailments that occur while taking medications should be reported to the center where the treatment course was prescribed. Monitoring patients involves identifying side effects and, if possible, eliminating them in one way or another.

No deviation can serve as a contraindication. The drug lines are designed in such a way as to select a medicine for each HIV-positive person. If there is a contraindication for taking one drug, then another one is selected that is similar in its effect. Since the purpose of ART is to save lives, there simply cannot be any absolute contraindications.

Side effects should not stop the patient: if you stop taking it, the disease will begin to progress quickly, and the terminal stage will occur much sooner than without treatment.

Today, a huge number of drugs are available that are suitable for all types of antiretroviral therapy for HIV, so you should not delay treatment. Before it is too late, please view the list of drugs for antiretroviral therapy on the website of the official distributor “Galaxy Super Specialty”.

AIDS and AIDS are incurable diseases, but their progression can be slowed through lifelong use of special medications. Combination antiretroviral therapy involves the use of three or four drugs, depending on the stage of the disease and the dosage prescribed by the doctor.

How does antiretroviral therapy work?

The immunodeficiency virus is highly mutagenic. This means that it is highly resistant to various adverse effects and is capable of changing its RNA, forming new viable mutations. This property significantly complicates the treatment of HIV and AIDS, since pathogenic cells very quickly adapt to the drugs taken.

Antiretroviral therapy is a combination of 3-4 different medications, each of which has a special principle of action. Thus, taking several drugs ensures the suppression of not only the main type of virus, but also any of its mutations formed during the development of the disease.

When is antiretroviral therapy prescribed?

Naturally, the sooner treatment for HIV infection begins, the better it will be to stop the progression of the virus and improve the patient’s quality and life expectancy. Considering that the early symptoms of the disease usually go unnoticed, antiretroviral therapy is prescribed approximately 5-6 years after infection, in rare cases this period is extended to 10 years.