Anyone who has been involved with antiretroviral therapy in the past few years has experienced its ups and downs. This article will be of interest to everyone who has encountered HIV in their life, no matter your professional activity that connects you with HIV or a chronic disease that you or your relative has encountered.

We hope that the story described can also convince those who still doubt that effective treatment for HIV is currently not possible without antiretroviral therapy. The article is written in very clear language, betraying the emotions of activists, doctors and people with HIV.

Hope and first successes

The dawn of antiretroviral therapy—1987−1990. This period is associated with great hopes and the first modest successes of antiretroviral monotherapy (Volberding, 1990; Fischl, 1990). However, soon the results of the Concorde study (Hamilton, 1992; Concorde, 1994) deprived both patients and doctors of rosy illusions for several years. The first widely used antiretroviral drug was zidovudine: it underwent clinical trials in 1985, and began to be prescribed to patients in March 1987. There was great faith in it, but at first the results of its use were, to put it mildly, not impressive. The same thing happened with other nucleoside reverse transcriptase inhibitors - zalcitabine, didanosine and stavudine, which appeared in 1991-1994.

There were no other serious options for treating HIV infection at that time, and for several years all disputes were limited to discussing the effectiveness of available drugs and their regimen. In particular, for a very long time, experts could not agree on whether patients should wake up at night to take the sixth dose of zidovudine. Many patients infected with HIV in the early or mid-1980s began to die. Hospices opened, new support groups for patients and outpatient nursing services appeared. AIDS and the high mortality rate associated with it have become commonplace. At the same time, obvious successes have been achieved in the fight against opportunistic infections: trimethoprim/sulfamethoxazole, pentamidine, ganciclovir, foscarnet and fluconazole have prolonged, albeit briefly, many lives. Some doctors began to seriously rely on “comprehensive prevention.” But in general there was hopelessness around HIV-positive people. Many people remember how gloomy and depressing the atmosphere was at the IX World AIDS Conference in Berlin in June 1993. From 1989 to 1994, HIV incidence and mortality rates increased enormously.

New class - protease inhibitors

However, soon - in September 1995 - the attention of the medical community was attracted by the results of the European-Australian study DELTA (Delta, 1995) and the American study ACTG 175 (Hammer, 1996). From them it followed that the combination of two nucleoside reverse transcriptase inhibitors was more effective than monotherapy. Indeed, the incidence of two adverse clinical outcomes (AIDS and death) was significantly lower with dual-component therapy. Both studies showed that it appears to be critical to prescribe two drugs at once, rather than using them in sequence. There is no doubt that there has been a breakthrough in antiretroviral therapy. By that time, the first studies of drugs of a completely new class—protease inhibitors—had been going on for several months. They were created in scientific laboratories based on data on the molecular structure of HIV and its protease. Their clinical significance seemed unclear.

Meanwhile, preliminary results of clinical trials of protease inhibitors became known, and rumors gradually began to spread about their effectiveness. In the fall of 1995, a fierce battle broke out between three pharmaceutical companies (Abbott, Roche and MSD). In an effort to bring the first protease inhibitor to market, each of them conducted intensive clinical trials of its drug - ritonavir, saquinavir and indinavir. Researchers did not leave clinical sites for weeks, processing observational data and thousands of questionnaires at night. As a result of this hard work, from December 1995 to March 1996, all three drugs were approved for the treatment of HIV infection: first saquinavir, then ritonavir and finally indinavir.

Many doctors did not know what exactly happened during these months. AIDS has not disappeared. Patients still died: few of them participated in trials of protease inhibitors, and those who received truly effective therapy, consistent with our modern understanding, were even fewer. Doubts remained. Too many times in recent years, hopes for miracle cures have been dashed. In early January 1996, everyone was concerned about other problems: palliative care, treatment of cytomegalovirus infection, infection caused by Mycobacterium avium-intracellulare, HIV cachexia and pain, organization of outpatient infusion therapy, and even euthanasia.

Reducing AIDS deaths

In February 1996, at the Third Conference on Retroviral and Opportunistic Infections in Washington, the evening session was left breathless by Bill Cameron's report on the first results of the ABT-247 trial. The audience froze. Shocked listeners learned that simply supplementing therapy with an oral solution of ritonavir led to a reduction in mortality among AIDS patients from 38% to 22% (Cameron, 1998). Antiretroviral therapy has never seen such sensational results!

Unfortunately, combination antiretroviral therapy came too late for many patients: it has been widely used since 1996. Some of the seriously ill patients managed to resist AIDS, but even in 1996 it killed many. While AIDS-related deaths in large HIV treatment centers were halved in 1996 compared with 1992 (Brodt, 1997), in smaller centers one in five patients still died from AIDS.

However, the potential for new drugs gradually became more apparent, and in June 1996 the World AIDS Conference in Vancouver turned into a veritable celebration of protease inhibitors. Even regular news programs talked in detail about “anti-AIDS cocktails.” The astonishingly unscientific term “highly active antiretroviral therapy” (HAART) circulated uncontrollably. The doctors were too happy not to get caught up in the general enthusiasm.

“Strike HIV earlier and harder!”

By then, Dr. David Ho, Time magazine's 1996 Person of the Year, had completed research that shed light on the HIV life cycle, which had previously been widely misunderstood (Ho, 1995; Perelson, 1996). The slogan “Beat HIV earlier and harder!”, proclaimed by Dr. Ho a year earlier, has now been taken up by almost all doctors. Having learned that HIV constantly and more actively reproduces in the human body, mercilessly, day after day, destroying CD4 lymphocytes, no one thought anymore about the “latent phase of HIV infection” and could not imagine life without antiretroviral therapy. In many HIV treatment centers, virtually all patients received HAART. In just three years, from 1994 to 1997, in Europe the proportion of patients not receiving antiretroviral therapy fell from 37% to about 9%, while the proportion receiving HAART increased from 2% to 64% (Kirk, 1998).

The situation was developing favorably. By June 1996, the first non-nucleoside reverse transcriptase inhibitor, nevirapine, was approved and a new class of antiretroviral drugs came into use. Another protease inhibitor has appeared - nelfinavir. The drugs seemed to be tolerated normally in most cases. Do I need to take 30 tablets per day? Please, if only it helps! The number of AIDS cases has dropped sharply. From 1994 to 1998, that is, in just 4 years, the incidence of AIDS in Europe decreased by more than 10 times - from 30.7% to 2.5%. The incidence of some serious opportunistic infections, especially cytomegalovirus infection and infection caused by Mycobacterium avium-intracellulare, has fallen even more noticeably. Ophthalmologists who dealt with eye diseases associated with HIV infection had to retrain. Large clinical trials aimed at treating opportunistic infections, launched just a few months earlier, stumbled due to a lack of patients. Previously wealthy hospices were forced to close or change their scope of activity. The first patients began to return to work. Outpatient nursing services were losing clients. The AIDS wards were now filling up with other patients.

In 1996 and 1997, the first complaints of patients about insatiable appetite and weight gain were heard. But is this really a bad thing after so many years of exhaustion and parenteral nutrition? Yes, and protease inhibitors include lactose with gelatin, and as a result of low viremia, energy consumption decreases. In addition, experts considered that increased appetite is quite natural for patients, since their immune system and general well-being have improved. Perhaps the only thing that somewhat embarrassed the specialists was the thin faces of the overweight patients. Meanwhile, patient dissatisfaction with having to take handfuls of pills grew.

Lipodystrophy

In June 1997, the Food and Drug Administration (FDA) first reported an increased risk of diabetes mellitus with protease inhibitors (Ault, 1997). In February 1998, the Conference on Retroviral and Opportunistic Infections in Chicago finally convinced doctors that protease inhibitors were not as selective as had long been thought. Poster followed poster, and now the entire wall was filled with photographs of patients with huge bellies, “bull humps,” thin arms and legs, and thin faces. And at the beginning of 1998, a new concept appeared - lipodystrophy. From now on, it will have a huge impact on antiretroviral therapy. The ancient medical wisdom has once again been confirmed - now also in relation to HAART - all good drugs have side effects. Meanwhile, the true cause of lipodystrophy remained completely unclear. But already at the beginning of 1999 in the Netherlands, there was an assumption that lipodystrophy was caused by the toxic effect of drugs on mitochondria. Today, everyone who treats HIV infection knows about this.

Three years of treatment with antiretroviral drugs and cure

Like so many other hopes, the hope of completely eradicating (and curing) HIV infection, which initially seemed so feasible, also faded. Of course, mathematical models are not capable of providing accurate predictions. But in 1997 they were relied upon: it was then believed that the complete and final destruction of HIV in the body would require at most three years of treatment with antiretroviral drugs in therapeutic doses.

Destruction was the magic word of those times. However, the period initially allotted for it increased with each subsequent conference. Predicting natural phenomena is not so easy, and new research data has made everyone sober up: it turned out that HIV, even after long-term suppression, remains latent in cells. Until now, no one knows how long these infected cells can live and whether a few such cells are enough for the infection to flare up again without treatment. Finally, at the World AIDS Conference in Barcelona, ​​experts agreed on the bleak fact that it is impossible to rid the body of HIV. According to the latest data, this would require an HIV-positive person to take antiretroviral drugs for 50-70 years. For now, only one thing can be said for sure: in the next 10 years, HIV infection will not become curable.

Lifelong treatment for HIV infection

Today, it seems more reasonable to think not about the destruction of HIV, but about the possibility of long-term, lifelong treatment of HIV infection - the same as for any chronic disease, say, diabetes. However, this means that patients will have to take the drugs for many years, observing the strictest discipline. Anyone familiar with the treatment of diabetes will understand the challenges faced by doctors and patients, and how important it is to improve antiretroviral drug combinations in the coming years. Not every HIV-positive person has such self-discipline and such mental and physical strength to not deviate one step from the treatment regimen for ten, twenty, or even thirty years in a row and take medications several times a day at the same time. Fortunately, this doesn't seem to be necessary. Antiretroviral therapy regimens are being improved and updated. We are approaching regimens in which the drugs will need to be taken once a day, and maybe even just twice a week.

As evidence of the adverse effects of antiretroviral therapy has increased over the past three years, many practitioners have made significant changes in their approach to antiretroviral therapy. By 2000, many of the strict recommendations of previous years had been revised. Today, what you hear more often is not “Hit HIV early and hard!” but “Hit HIV as hard as you can, but only when necessary” (Harrington and Carpenter, 2000). Now the main subject of long discussions has become a simple question: “When to start treatment?” The answer to this often requires extreme caution.

No matter what skeptics say, we must not forget about the possibilities of HAART. She is capable of miracles! Thanks to HAART, cryptosporidiosis and Kaposi's sarcoma are completely cured, even progressive multifocal leukoencephalopathy can be managed, and the need for the prevention of cytomegalovirus infection disappears. But the main merit of HAART is a significant improvement in the well-being of patients, although some public figures and AIDS consultants do not want to admit this.

Skepticism about HAART is partly due to the fact that many young Western doctors, who only began treating HIV in the late 1990s, simply do not know what AIDS is. For them, AIDS is a rarity, a serious case, the development of which can be stopped. They did not find the “stone age” of the fight against AIDS.

The principle of evidence-based medicine

Perhaps, doctors involved in the treatment of HIV infection, like no other, should, while remaining open to new methods, remember the “Stone Age” of their specialty. Anyone who is categorically against interrupting therapy and stubbornly adheres to rigid schemes not only remains aloof from modern realities, but also loses his sense. Anyone who does not bother to acquire new knowledge and does not attend special conferences several times a year will not be able to properly treat their patients, because approaches to treating HIV infection change at least every two to three years.

Anyone who strictly follows the principles of evidence-based medicine and in their practice does not deviate one step from official recommendations quickly lags behind life. HIV medicine is constantly evolving. Recommendations are still just recommendations. Many of them were already outdated at the time of their release. There are no immutable rules in this area. At the same time, anyone who accepts the randomness of choice as freedom, or believes that the data of fundamental research can be ignored, is also mistaken. An individual approach to treatment does not mean that you can treat as you please. In addition, it should be remembered once and for all: the doctor shares responsibility for poor compliance with the treatment regimen with the patient. And one more thing. Even many experienced doctors neglect an important rule: every patient has the right to know why he was prescribed or not prescribed this or that treatment.

The question that concerns every patient with HIV infection is treatment of the disease. Currently, there are no drugs that act on a dormant virus, until we can “expel” the virus from the cells that it has infected once it enters the patient’s body. After the initial infection, the immune system produced antibodies and recruited specific killer cells that independently coped with the first attack of the virus. In the asymptomatic stage is installed balance: there is a certain amount of antibodies in the blood, sufficient to restrain the multiplication of the virus and its damage to new immune cells, which is what testifies restoration of the number of CD4 cells in the blood and their stable numbers over a long period. But this balance can be periodically disrupted for a variety of reasons: the presence of concomitant diseases, acute viral infections, drug use, lack of protein in food, etc. - they reduce the number of specific antibodies and stimulate the reproduction of the virus. As a result, new viral particles infect healthy cells of the immune system, and the next laboratory examination reveals a decrease in the level of CD4 cells. The body can repel such viral attacks for a long time, restoring the number of CD4 lymphocytes.

But gradually (how quickly depends on the initial state of the immune system and the virus itself) the reserves of the body’s immune system are depleted, and the number of CD4 cells ceases to recover. The patient requires specific treatment - ART, which prevents the multiplication of the virus, and, consequently, its progressive damage to cells of the immune system.

What is ART?

ART - antiretroviral therapy- involves the use of three (at least two) drugs that stop the replication of HIV. Like all viruses, HIV is extremely variable and quickly adapts to medications. Therefore, ART involves the use of a combination of drugs that immediately affect both stages of viral reproduction. There are no drugs yet that act on the dormant virus, but ART stops HIV from reproducing and therefore reduces the amount of virus in the blood.

Antiretroviral therapy prevents the replication of the human immunodeficiency virus by acting on 2 stages:

To reproduce, HIV uses the DNA of the host cell, since it does not have its own. The transfer of information from viral RNA to the DNA of the host cell involves the viral enzyme, revertase. Drugs from the group of non-nucleoside reversetase inhibitors (viramune, stokrin) block this enzyme and disrupt the construction of viral DNA. Drugs from the group of nucleoside analogues of reversetase replace the building material of viral DNA and prevent its creation (timazide, zerit, Videx, hivid, epivir).

If the virus nevertheless manages to create viral DNA, the process of forming viral particles from it begins, which are “dressed” in a protein shell by another viral enzyme - protease. This enzyme is blocked by drugs from the group of protease inhibitors: invirase, Crixivan, Viracept, Kaletra - newborn viral particles remain undressed and cannot infect host cells.

Aggressive therapy includes drugs that act on both processes and consists of 3-4 drugs.

Before starting treatment, the patient must remember that:

1) It is necessary to observe the main condition of antiretroviral therapy - to avoid interruptions in taking the drug, to strictly observe the hours of taking the drug. If this rule is neglected, ART will turn out to be not only useless, but also harmful, since HIV constantly mutates during reproduction, and with the next missed dose of medication the virus will begin to multiply and create viruses that will be resistant to the drugs used (i.e., resistance develops). Thus, the less chance the virus has to reproduce, the less the risk of developing resistance to ART.

2) Like most drugs, ART drugs have side effects that the patient should be familiar with before treatment. The most common of them are nausea (AZT, Hivid), rash (Ziagen, Viramune), liver toxicity (Videx, Virumune, Hivid ), neuropathy (zeritis, chivid). With long-term use of protease inhibitors, cholesterol levels may increase (risk of cardiovascular diseases), and lipodystrophy may develop - redistribution of body fat (reduction in the face and limbs, deposition in the neck, hips and abdomen). Therefore, during the treatment process, you need to visit your doctor monthly, and if suspicious symptoms occur, immediately report them to the doctor.

3) It is necessary to study the medication regimen. For example, saquinavir and ritonavir should be taken with food, while indinavir and didanosine should only be taken on an empty stomach. 4) It is very important to tell your doctor what medications you are taking in addition to treating HIV infection. Because when drugs from different groups interact, dangerous side effects may develop or the effectiveness of ART drugs may decrease.

HIV nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, phosphazide, stavudine, didanosine, zalcitabine, abacavir

Non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs): nevirapine, efavirenz

HIV protease inhibitors (PIs): saquinavir, indinavir, ritonavir, nelfinavir, amprenavir

Combination drugs (lamivudine/zidovudine)

Mechanism of action. NRTIs block HIV reverse transcriptase and selectively inhibit viral DNA replication. NNRTIs block RNA- and DNA-dependent polymerase. PIs block the active site of HIV protease.

Pharmacokinetics.

Table 26.13. Pharmacokinetic characteristics of some ARPs

Preparation	Bioavailability, %		Metabolism	Removal
Zidovudine			Liver (P450)
Ifavirenz			Liver (P450 inducer)
Indinavir			Liver (P450 inhibitor)

Adverse reactions. Poor tolerability of ARP is one of the most important reasons for low compliance with therapy and high incidence of ARP discontinuation. NRTIs are more likely to cause mitochondrial toxicity, lactic acidosis, peripheral neuropathy, and bone marrow suppression; for NNRTIs - CNS damage; for IP – lipodystrophy, hyperlipidemia, nephrolithiasis.

Drug interactions. You cannot prescribe drugs from the NRTI group that are analogues of the same nucleotide. It is necessary to pay attention to whether ARP is an inducer, inhibitor or substrate of the cytochrome P450 system.

Indications. Treatment and prevention of HIV infection.

Contraindications. Hypersensitivity, breastfeeding, pregnancy, renal, liver failure.

Features of clinical use in various categories of patients. Prescribing zidovudine to pregnant women infected with HIV significantly reduces the risk of infection of the child. Zidovudine, didanosine, stavudine, abacavir, nelfinavir, ritonavir, efavirenz, amprenavir, zalcitabine, saquinavir are approved for use in children.

Chemoprophylaxis of parenteral HIV infection

It is used when health workers are injured by instruments contaminated with HIV. If more than 72 hours have passed since possible infection, chemoprophylaxis is considered inappropriate. The regimen is selected depending on the characteristics of the patient who is the source of HIV infection.

Basic mode: zidovudine 0.6 g/day in 2-3 doses + lamivudine 0.15 g every 12 hours.

Advanced Mode: one of the basic regimens + indinavir 0.8 g every 8 hours or nelfinavir 0.75 g every 8 hours or 1.25 g every 12 hours or efavirenz 0.6 g once a day or abacavir 0.3 g every 12 hours.

26.3. Antifungal drugs Indications for use in dentistry

In dental practice, antifungal drugs are most often used topically for the treatment of oral candidiasis, which is classified as superficial candidiasis. The latter are characterized by damage to the mucous membranes (oral cavity, esophagus, vagina) and skin. If the immune system is impaired, the infection becomes chronic and can develop into a systemic form with damage to internal organs. The most severe form is invasive candidiasis. For systemic lesions except C. albicans pathogens such as Aspergillus spp ., Rhizopus spp. , Fusarium spp . and other mushrooms.

Yeast fungi of the genus Candida are permanent inhabitants of the oral cavity. Against the background of the use of antibiotics and immunity disorders (diabetes mellitus, cancer, taking immunosuppressive drugs, HIV infection), they can cause oral candidiasis, which manifests itself in the form of aphthous stomatitis, candidal leukoplakia, “prosthetic” stomatitis, drug stomatitis and mucocutaneous forms of damage. Cadida stomatitis may be a manifestation of a systemic fungal infection.

Classification

Antifungal drugs, depending on their chemical structure, are divided into several groups that differ in their spectrum of activity, pharmacokinetics, tolerability and indications for use (see Table 26.14).

Table 26.14. Classification of antifungal drugs

		REPRESENTATIVES
		Nystatin
		Natamycin
		Amphotericin B Liposomal Amphotericin B
	For systemic use	Ketoconazole
		Fluconazole
		Itraconazole
	For topical use	Clotrimazole Miconazole
		Bifonazole
Allylamines		Terbinafine
		Naftifin
Echinocandins		Caspofungin

The importance of drugs such as potassium iodide, griseofulvin, chlornitrophenol, and flucytosine has now significantly decreased.

Antiretroviral drugs

Nunquam periculum sine periculo vincemus

(Danger is never conquered without danger)

Oddly enough, it is the simplicity of the virus that makes it very difficult to fight it. Treatments such as boiling or strong acid, which easily kill the virus, are not suitable for treating humans. Safer remedies, such as antibiotics, which work well against bacteria, cannot help in the case of a virus, since they have no effect on it. Although the search for drugs began immediately after the discovery of HIV and certain successes were certainly achieved, the treatment of HIV infection remains a very complex and only partially solved problem.

Medicines that act on HIV (suppress its reproduction) are called antiretroviral drugs. Some data can be cited indicating that already in the early stages the use of HIV therapy gave a certain result: in 1986, over 70% of those infected with the virus in the previous two years developed AIDS or died. Among those infected in 1989, there were only 20% of them, since the first antiretroviral drug, azidothymidine, was introduced into the practice of treating patients, which became the basis for all subsequent combination therapy regimens.

Today, many antiretroviral drugs that target HIV are used to treat AIDS. Treatment with these drugs is called antiretroviral therapy (ABRT) or antiretroviral therapy (ART). The currently available arsenal of drugs makes it possible to suppress viral replication in a significant proportion of patients for a certain, sometimes quite long period, and transform the disease into a chronic course. ART quite often suppresses the virus so much that even very sensitive tests sometimes fail to detect its presence in the blood (although it remains there!). However, it does not provide a complete cure for HIV infection. This therapy can only prolong the patient’s life, but it is not possible to completely stop the infectious process. In addition, antiretroviral drugs act not only on the virus, but also on the cell itself. Unfortunately, almost all modern antiviral drugs are highly toxic, much more so than antibiotics. According to Luc Montagnier (1999), we have learned to treat only superinfections HIV/AIDS, but not AIDS itself.

Nevertheless, the development of medical science in the field of treating HIV infection is occurring very rapidly. Almost every year, and sometimes even month, messages appear about the discovery of new funds. In most cases, the authors present wishful thinking, and journalists “buy” into this and spread the “sensation” around the world. But there are also serious developments that are created in different laboratories around the world and are carefully tested both in animal experiments and in clinical trials on humans. Thus, it is possible that the information presented here may be significantly supplemented by the time our book is published.

So, antiretroviral drugs act specifically on the virus, blocking the action of one or another of its enzymes and thereby preventing the virus from multiplying in lymphocytes. At the end of 2003, about two dozen drugs were approved for use in medical practice. Depending on the principle of action and target, all modern antiretroviral drugs are divided into several classes: reverse transcriptase inhibitors (nucleoside - NRTI, non-nucleoside - NNRTI, nucleotide), protease inhibitors (PI), integrase inhibitors (II) and fusion inhibitors. The word "inhibitor" means "delaying, stopping." Various drugs suppress the virus at different stages of its life cycle (Fig. 29). As mentioned above, reverse transcriptase and protease are enzymes without which HIV is unable to reproduce in the human body. Reverse transcriptase inhibitors prevent the enzyme from synthesizing its DNA copy on viral RNA, and protease inhibitors prevent the formation of new viral particles, since proteins of the required size with certain functions are not formed from the large precursor protein. There are also drugs that prevent the virus from entering cells. In Fig. Figure 29 depicts those parts of the virus life cycle that are affected by numerous modern drugs. As a result of inhibition of certain links, the reproduction of the virus should stop or at least slow down significantly. As they said in ancient times, cessante causa, cessat effectus - with the cessation of the cause, the effect ceases.

Rice. 29. The rectangles in the figure represent the currently available antiretroviral drugs. Thick arrows indicate the HIV life cycle processes they target. NNRTIs - non-nucleoside reverse transcriptase inhibitors, NRTIs - nucleoside reverse transcriptase inhibitors, II - integrase inhibitors, PIs - protease inhibitors. Other explanations are given in the text

ART is used only as prescribed and under the supervision of a physician in strict accordance with the instructions. There may be harmful and unpleasant side effects when taking antiretroviral drugs. Only a specialist can choose the right combination. There is another problem with the use of HIV inhibitors. The mechanisms of interaction between the human body, the virus and drugs are very complex and have not yet been fully studied. As a rule, at first, HIV inhibitors have a significant effect on it, but with long-term use of antiretroviral drugs they cease to have their positive effect. Viruses circulating in the patient’s body after ART often become insensitive to drugs and the effectiveness of treatment is sharply reduced. This condition is called HIV resistance, or resistance.

The problem of microbial resistance to drugs has been around for a long time. Doctors first encountered this when they began to use antibiotics, in particular penicillin, to combat bacterial pathogens. At first, the effect was impressive. However, it did not last long: many microbes have learned to produce a special enzyme, beta-lactamase, which easily decomposes penicillin and similar drugs. Since then, a kind of arms race has begun, in which doctors are developing new antibiotics, and bacteria are developing means of protecting against them. Viruses change in approximately the same way - thanks to mutations, they develop mechanisms of defense against existing medications directed against them. Simply put, the development of microorganisms occurs according to Darwinian laws: when a person creates unfavorable conditions for microbes, the fittest survive.

A similar situation arose after the introduction of antiretroviral drugs. HIV resistance to medications is usually due to the fact that the virus very quickly changes its genetic structure (mutates) during the process of reproduction. Some of the “mutants” become insensitive to the drug; the drug no longer prevents the reproduction of the virus, and this entails the progression of the disease. As a result of this, even those forms are selected that can reproduce normally... only in the presence of this drug. That is, they have an addiction that is sometimes called “viral substance abuse.”

It should also be borne in mind that when resistance to one type of HIV inhibitor develops, resistance to another type of antiretroviral drugs may simultaneously develop, even if these drugs have not yet been used. This phenomenon is called cross-resistance, and, unfortunately, it occurs quite often. And it is by no means easy to find a new combination of drugs to which the virus still retains sensitivity, despite the fact that at the moment there are quite a large number of such combinations of HIV inhibitors. However, combination therapy leaves the virus less likely to develop resistance to the drugs.

It has now been established that HIV often becomes resistant to drugs due to the fault of the patient himself. The main reason here is improper medication use. If a medication prescribed by a doctor is taken irregularly, intermittently, the virus uses it and acquires resistance to it. Further treatment with this drug becomes useless. Something similar happens to those who take antibiotics irregularly. In this case, the bacteria become insensitive to treatment, and cure now requires stronger antibacterial agents prescribed for a longer period. It has been reported that in the United States, approximately 30% of HIV-infected people treated with ART already have the virus that is resistant to treatment.

To avoid this, doctors recommend strictly following all their instructions. If you are prescribed to take the medicine twice a day, then within a week you must take 14 doses and no less, otherwise the treatment will not make any sense. It is also very important to take the medicine at a certain time so that its concentration in the blood remains at a certain level. In other words, if you do it, do it well!

It has been found that patients who received information about the treatment of HIV infection are more likely to adhere to their antiretroviral drug regimen. Such people, with access to understandable information about HIV, find it easier to communicate with their doctors, they better understand their condition, tolerate treatment more easily, and use it more successfully for the benefit of their health. Research shows that patients who know more about their disease live longer and stay healthier longer.

LECTURE No. 9. Analgesics and non-steroidal anti-inflammatory drugs. Oxinames and gold preparations 1. Analgesics. Narcotic analgesics Analgesics are drugs that selectively relieve pain.

LECTURE No. 10. Non-narcotic antitussive drugs. Emetic and antiemetic drugs 1. Non-narcotic antitussives This group includes drugs that do not have the side effects inherent in opioids. There are drugs with a central

1. Preparations containing essential oils. Preparations containing menthol These drugs excite receptors located in the skin and mucous membranes, impulses from which enter the central nervous system. This causes a reaction on the part of organs that have associated innervation in the central nervous system with

Sulfonamide drugs These are synthetic substances that have a bacteriostatic (disturbing the life of bacteria) effect on various microbes: staphylococci, streptococci, pneumococci, etc., pathogens of intestinal infections (dysentery, typhoid fever and

Plays a big role. It is prescribed only by a qualified doctor based on tests, other clinical and laboratory studies, as well as the general condition of the patient. Of course, it is impossible to cure the disease completely with its help. But to alleviate the patient’s condition and significantly prolong his life is quite possible. Antiretroviral therapy is most often used for HIV infection. It implies an impact on several problems caused by the immunodeficiency virus. When is such treatment used, and what types does it consist of?

HIV infection, ART therapy: general information

Treatments for AIDS have been in development for decades. Today, high antiretroviral therapy is recognized as the most effective. Before describing its effectiveness and focus, it is necessary to find out when such treatment begins to be used and who needs it. It is known that antiretroviral therapy for HIV infection is not used immediately after diagnosis. It would seem that an infected person should be treated immediately. But that's not true. With such a diagnosis, it is very important not to harm the body with strong drugs. It is worth noting that approximately thirty percent of all infected people are carriers of the virus. They do not have an acute stage of the disease, and the incubation period immediately turns into a latent period, which lasts for decades. In such people, a terrible illness is diagnosed, as a rule, by accident, for example, during preparation for a planned operation, medical examination, and so on.

Taking HIV therapy in this case is considered inappropriate. Since the body does not react to the presence of an infectious agent in it. Using strong medications can weaken your immune system. In some cases, this can lead to the opposite effect. Then the person will turn from a carrier of the virus into an infected person with all the accompanying symptoms. AIDS therapy is not used even in the asymptomatic stage. We are also talking about patients in whom the acute stage manifests itself “in all its glory.” Treatment in their case directly depends on how the infected organism behaves.

Throughout the latent stage, such patients regularly visit the doctor and undergo tests. The decision about whether antiretroviral therapy for HIV is necessary in each specific case is made by a specialist based on some research. What is taken into account when making such a decision? Viral load. With regular testing, the viral load per milliliter of blood is determined from an infected patient. While it is within normal limits, the asymptomatic stage continues. An organism with a strong immune system has time to produce the required amount of antibodies that resist the virus. In this case, therapy for HIV infection is not needed.

In addition to the viral load, the immune status is also taken into account. We are talking about the quantitative composition of CD-4 cells. It is also determined through blood sampling. There are cases when the immune status and viral load are normal, but the patient gradually begins to show signs of secondary manifestations. We are talking about both concomitant diseases and opportunistic infections. In these cases, antiviral and retroviral therapy for HIV is necessary. And the sooner treatment begins, the more favorable the prognosis. It is important to consider that when deciding to prescribe certain drugs, the doctor must look at the dynamics of the immune status and viral load. The specialist needs to analyze how the patient’s condition changes over several months.

Based on monitoring the state of the immune system, a decision is made about what therapy for HIV-infected people is necessary at this stage of the disease. Only a doctor should prescribe treatment. After all, for each patient it is selected depending on the characteristics of the body and test results.

HIV treatment regimens: antiviral, immune and clinical directions

It is worth noting that HAART therapy used for HIV has several goals. It has a virological, general strengthening immune and clinical focus. Each of them should be considered in more detail. Antiretroviral drugs for HIV are taken in combination. The doctor prescribes several medications to the patient at once. Usually we are talking about three to four drugs. Virological drugs for HIV and AIDS are prescribed as therapy, which has not only the goal of suppressing the immunodeficiency virus itself.

As a rule, antiviral drugs are also needed to reduce the impact of concomitant diseases on the body if they have already manifested themselves. If the doctor decides to use such drugs at an asymptomatic stage, then the patient needs a powerful course of medications that suppress infected cells. Most often, this need arises when the viral load significantly exceeds the norm. In this case, it is impossible to do without treatment, which involves such AIDS therapy.

So, the main task of the antiviral effect on the body of an infected person is to reduce the production of infected cells and reduce their spread. The course of such antiviral therapy for HIV usually lasts from sixteen to twenty-four weeks. In this case, the suppression effect can be observed as early as the sixth week.

Immunological initial therapy for HIV is necessary in order to restore the immune system. She suffers greatly as her viral load increases. The immune status does not correspond to the norm. Taking medications that restore the immune system allows you to increase the number of CD-4 cells to normal.

Clinical ART therapy for HIV includes drugs that can extend the life of infected patients not by a year or two, but by decades. The risk of developing AIDS, which, as is known, quickly ends in death, is significantly reduced. With the help of this HIV treatment, HAART, it becomes possible for infected partners to conceive a child relatively safely. The risk of transmitting the virus through blood or sexual contact is also reduced.

The initiation and side effects of HIV therapy are closely related

When to start therapy for HIV is decided by a specialist, so immediately after diagnosis you need to go to a specialized hospital. However, the effectiveness of treatment largely depends on a person’s lifestyle and adherence to medical prescriptions, and, of course, on what therapy is prescribed for HIV. Here are some useful tips to help infected people begin the treatment prescribed by their doctor correctly:

It should be remembered once again that adherence to HAART for HIV infection is one of the important components of successful treatment.

Side effects and consequences of HIV therapy

HAART is a highly effective treatment with which the latent period of the immunodeficiency virus can last for decades, and AIDS does not develop at all. However, this approach to maintaining and restoring an infected organism, unfortunately, is not ideal. All the drugs the use of which he implies are toxic. Of course, this affects the internal organs and vital systems of the human body. That is why, before antiretroviral therapy that prevents AIDS is prescribed, the patient must undergo a lot of examinations and pass the necessary tests. This is necessary so that the attending physician can choose the most appropriate regimen. Regular visits to a specialist and a clear clinical picture will help the patient successfully balance on the line between suppressing the virus and the harm that drugs can cause.

When doctors prescribe therapy for HIV, they always warn the patient about possible side effects. This is extremely important, if only so that the patient can distinguish between the consequences of taking drugs with dangerous symptoms that may arise if the effectiveness of the treatment decreases. It is important to note here that antiretroviral therapy for HIV-infected people is a treatment that is well tolerated by most patients. Although it is often compared to chemotherapy, side effects from its use occur much less frequently and go away much easier.

Nausea and vomiting are the most common signs of a reaction to HAART. They may haunt the patient constantly or appear only occasionally. As a rule, nausea and vomiting appear in the first weeks of treatment. The patient should be warned about this by the doctor when it is necessary to start therapy for HIV.

Another common side effect is diarrhea. It occurs because drugs used to treat the immunodeficiency virus disrupt the flora in the intestines. That is why, when treating HIV, the consequences of the intestines should be eliminated by taking prebiotics. From the gastrointestinal tract, during the use of such drugs, appetite disturbances and pain in the epigastric region may also be observed. If the patient had an undiagnosed ulcer, this treatment may cause stomach bleeding.

Side effects of HIV therapy can also be observed in the central nervous system. This is a fairly rare phenomenon, occurring in only five percent of those infected.

There are a number of contraindications for HAART. For example, alcohol should not be taken at least a few days before the start. It is not used for acute renal failure or gastric bleeding. ART therapy for HIV can be started with a fever only if it is a consequence of one of the concomitant diseases. If this symptom appears due to a disease that is not related to the immunodeficiency virus, then it should be eliminated before starting treatment.

Gene therapy for HIV 2016: effective or not?

Gene treatment for immunodeficiency virus has been developed relatively recently. In 2016, it was adopted by some clinics in our country. Such HIV therapy is expensive in Russia, and some specialists qualified in the treatment of the immunodeficiency virus have little confidence in its effectiveness. Perhaps the reason is that not too much research has been done on the new method. Whether gene therapy helps with HIV is a question that is still difficult to answer.

It is based on the use of enzymes that remove infected tissue from the body. Some scientists believe that this treatment method can cause irreversible consequences. After all, intervention in the body at the genetic level is always unpredictable. The best HAART therapy for HIV infection should be decided by a qualified specialist.

Physiotherapy for HIV infection and other alternative treatments

Physiotherapy methods are not used as a treatment for the immunodeficiency virus. This type of therapy can be used to relieve symptoms of diseases caused by damage to the central nervous system.

Psychotherapy for HIV infection brings tangible results. Some patients need it, because living with such a diagnosis is extremely difficult. Much depends on the psychological state of the patient, including how HAART will affect his body.

Some private clinics today offer a service such as ozone therapy for HIV infection. Qualified specialists consider it insufficiently effective.