HIV - Treatment

Content

Introduction

Introduction

Treatment for HIV infection (from English Human Immunodeficiency Virus) is based on a multi-drug combination therapy, initially also called HAART (from the English Highly Active AntiRetroviral Therapy). HIV drugs are also referred to as antiretrovirals because the HIV virus belongs to the family of retrovirus.

Although a definitive cure for HIV infection is not yet available, the combined therapy has made it possible to reduce the mortality and progression of the disease caused by the virus (read the Hoax), making the life expectancy of a person with HIV now almost comparable to that of a healthy person of the same age.

Numerous drugs are now available for combination therapy. Most work by blocking the activity of enzymes (proteins that speed up and facilitate chemical reactions) specific to HIV and necessary for it to multiply in its target cells. These cells are represented by a subgroup of white blood cells, called CD4 + lymphocytes (ie lymphocytes that express a molecule called CD4 on their surface), which are part of the immune system and are essential for adequate defense against infections. The HIV enzymes blocked by these drugs are integrase, reverse transcriptase and protease.

Anti-HIV drugs are therefore classified as:

  • integrase inhibitors (the viral enzyme that integrates the viral genome into the host cell's DNA)
  • HIV reverse transcriptase inhibitors, divided according to the chemical structure into two classes: nucleoside / nucleotide inhibitors (analogues of the constituents of RNA and DNA), non-nucleoside inhibitors
  • protease inhibitors (an enzyme that can "break up" proteins)
  • fusion inhibitorswhich block the entry of HIV into CD4 + lymphocytes

Most of these drugs work by deactivating enzymes (substances that speed up and facilitate chemical reactions) that the virus uses to reproduce (replicate).

Antiretroviral therapy is able to effectively suppress the quantity (viral load) of the virus in plasma (HIV-RNA), reducing the risk of HIV transmission between partners by sexual route and the risk of transmission from mother to newborn during pregnancy and childbirth (vertical transmission of HIV).

For antiretroviral (anti-HIV) therapy to be effective, it is therefore necessary to ensure that HIV is no longer detectable in the blood.This objective is achievable only if several antiretrovirals are used together. With less potent treatments, HIV continues to be present in the blood, to multiply and to weaken the immune defenses, and in a short time it inevitably becomes resistant to the drugs used and renders them ineffective. It is possible to identify the presence of drug-resistant viruses with tests specific, and in these cases the drugs for which resistance has been identified are replaced with drugs for which sensitivity has been maintained, usually of different classes.

In any case, antiretroviral drugs are not able to eliminate HIV from the organism because HIV remains permanently present in already infected cells. The therapy therefore has the objective of stopping the multiplication of the virus in a lasting way. Once initiated, therapy must be followed forever, and cannot be interrupted or carried out partially or intermittently. There are currently no drugs with prolonged activity to be taken once a week or a month, and it is therefore necessary to take antiretroviral therapy every day respecting the doses and times indicated. However, today very simple combinations are available, in which it is possible to take all the planned therapy in a single administration per day, sometimes represented by a "single tablet to be taken in the evening. The control of antiretroviral therapy is based on the regular determination of viral load. , CD4 + lymphocytes and common blood tests (eg liver function, kidney) to highlight any toxicity.

To learn more about the topic, it is possible to consult the "Italian Guidelines on the" use of antiretroviral drugs and on the diagnostic-clinical management of people with HIV-1 infection "drawn up by the Ministry of Health.

HIV: when and how to start therapy

HIV: when and how to start therapy

Combined HIV therapy (or antiretroviral therapy or HAART) must necessarily be prescribed by the doctor and is recommended, after having ascertained (diagnosed) the presence of the virus, even in the absence of particular disorders or symptoms, and regardless of the level of immunodeficiency ( that is, an inefficiency of the immune system) to which the infection led. In fact, it has the purpose of stopping the progressive decrease of CD4 + lymphocytes which, over time, is responsible for the severe immunodeficiency characteristic of AIDS (the most advanced phase of HIV infection in which the symptoms of opportunistic diseases occur, ie diseases due to the opportunity that some infectious agents have to infect the individual who has few defenses).

Before starting the therapy, it is necessary to measure with a blood sample the amount of circulating virus (viral load) and the levels of CD4 + lymphocytes present. Starting therapy in the early stages of the disease increases the chances of a full recovery of the immune system by reducing the likelihood of contracting the many opportunistic diseases associated with HIV infection, including some particular types of cancer.

The recommended regimens are different, and are periodically updated by national and international guidelines based on the results of clinical studies. Situations that may require special regimes include:

  • pregnancy, antiretroviral therapy is always recommended in pregnant women to prevent the transmission of the HIV virus from mother to child. However, antiretroviral (anti-HIV) drugs that pose no risk to the mother and the unborn child should be used. Without antiretroviral therapy the transmission risk is 1 in 4, while with therapy it is almost zero
  • hepatitis B (antiretrovirals active on both HIV and HBV, the hepatitis B virus, must be used)
  • tuberculosis, hepatitis C, other infections associated with HIV infection (regimens must be defined according to pharmacological compatibilities)
Response to treatment

Response to treatment

During therapy, the doctor checks the amount of virus present in the blood (viral load) approximately every three months, for the first year and every 6/12 months thereafter, once the viral load in the blood has dropped to levels that are no longer detectable.

Once treatment is started, CD4 + lymphocyte levels are likely to gradually increase again. The times, however, vary considerably from person to person: in some cases it takes months or even years before the CD4 + lymphocytes return to normal values. Generally, if their numbers were low at the start of treatment, recovery is more likely to be slower.

To date, the vast majority of people under treatment remain in good health. The response to therapy depends on various factors which include individual characteristics of the person, the type of infecting virus, the presence of concomitant pathologies, and above all the regularity in taking the drugs.

Side effects

Side effects

The undesirable symptoms associated with antiretroviral therapy (side effects) vary depending on the combination used. We can observe, for example:

  • nausea and vomit
  • diarrhea
  • skin rashes
  • headache
  • insomnia
  • tiredness

The long-term effects on various organs and systems are also variable depending on the combination used, and include:

  • damage to kidney function
  • alterations in metabolism, with increases in the blood levels of LDL cholesterol, triglycerides (blood fats), and blood glucose (sugars), with increased risk of heart and metabolic diseases
  • damage to the function of the liver (hepatic)
  • alterations in bone metabolism (with greater bone fragility)

In the event that serious and uncommon undesirable effects (side effects) appear, the doctor may modify the current therapy in one or more of its components and prescribe a different combination of antiretroviral drugs.

Although current therapies are already very effective, future goals of treatment aim to select regimens that are increasingly effective and tolerable in the long term, reducing as much as possible the undesirable effects of drugs and the frequency of administration, to allow the person with the " HIV an ever better quality of life.

Reduction of the risk of HIV transmission with antiretroviral therapy

Reduction of the risk of HIV transmission with antiretroviral therapy

Combined antiretroviral therapy, as mentioned, plays an important role in reducing the risk of transmission. Its main methods of application in this area are as follows:

  • treatment as prevention, the appropriate and regular intake of antiretroviral drugs by the person with HIV effectively prevents its transmission. This effect is achieved through stable suppression of viral replication. Studies carried out on HIV-discordant couples (ie formed by an infected and a non-infected partner) have shown that the maintenance of a stably undetectable viral load is associated with a condition of non-transmissibility of the infection through sexual intercourse. The formula that summarizes this situation is U = U (undetectable = untransmittable, that is, not detectable = not transmissible)
  • pre-exposure prophylaxis o PrEP, is a method of prevention of HIV transmission in which people who are not infected with HIV but at high risk of infection (to be assessed by healthcare personnel) take continuous (daily) or intermittent ("on demand") drugs anti-HIV to reduce the risk of transmission associated with sexual intercourse or injecting drug use. It can also be offered to HIV-serodiscordant couples who are going to conceive naturally. The recommended regimens provide for the intake of only one tablet per day, represented by a combination of two anti-HIV drugs. Adherence is an essential element for the success of PrEP. Its intake can cause side effects, usually mild. PrEP is not effective on other sexually transmitted diseases, for which risk reduction requires the use of a condom
  • post-exposure prophylaxis o PEP, is represented by a short course of therapy with anti-HIV drugs, to be taken at short intervals (as soon as possible, and in any case no later than 72 hours) from a possible exposure to HIV by HIV-negative people or with unknown HIV status. The recommendations envisage its use following a risk assessment by healthcare personnel. The probability of transmission correlates significantly with the concentration of HIV in the material to which one is exposed, be it blood or genital secretions. It is mainly used in the event of accidents in healthcare or laboratory personnel exposed to HIV (occupational prophylaxis) and for unprotected sexual intercourse in emergency situations (non-occupational prophylaxis, such as condom rupture, sexual violence). The drugs are taken for four weeks. Side effects are possible and its effectiveness is not 100%, depending on various factors, including time interval between exposure and start of treatment and extent of exposure In-depth link

    In-depth link

    Ministry of Health. HIV / AIDS, 2017 edition of the guidelines on the treatment and clinical management of the patient

    Higher Institute of Health (ISS). ISS news reports reporting Italian data on HIV / AIDS

    United Against Aids (ISS)

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