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Communicable Diseases Module: 22. Introduction to Antiretroviral Therapy

Study Session 22  Introduction to Antiretroviral Therapy

Introduction

In this study session you will learn about the main therapy used to treat people living with HIV (PLHIV), and its benefits and goals, so that you will be able to help patients get the full benefits of the treatment, and maintain their health for as long as possible. The treatment used for HIV-positive people is called antiretroviral therapy, which can be shortened to ART. It consists of giving drugs termed antiretrovirals (ARVs), which work by attacking the human immunodeficiency virus (HIV) itself.

For ART to be successful, you should be aware of two things. First, ARV drugs should be given in the correct way; that means using a combination of three ARVs which act on the virus differently. Secondly, ART should be given continuously as a lifelong treatment. In addition to improving the quality of life for patients, ART also has the benefits of reducing stigma and discrimination, and increasing the chances of PLHIV going to HIV/AIDS services to ask for help.

Even though you are not expected to prescribe ART for patients, you need to be familiar with the basic concepts and the most common adverse side-effects of the drugs. This information will help you to provide good care for PLHIV who are being treated with ARVs. Remember that drug treatments for chronic diseases require adherence, which means taking medications as instructed by the prescribing health professional. It is also important for you to trace ‘treatment defaulters’ (PLHIV who stop taking their medications), to reduce the consequences for the patient, and for public health at large.

Adherence and defaulter tracing, in the context of HIV/AIDS, are discussed in Study Session 23 of this Module.

Learning Outcomes for Study Session 22

When you have studied this session, you should be able to:

22.1  Define and use correctly all of the key words printed in bold. (SAQs 22.1 and 22.2)

22.2  Explain what antiretroviral therapy (ART) is, and its goals and benefits. (SAQs 22.1, 22.2 and 22.4)

22.3  Explain why three antiretroviral (ARV) drugs are needed for effective ART and how they can be combined. (SAQ 22.3)

22.4  State the four first-line ARV regimens, their common side-effects, and describe what you should do if these side-effects occur. (SAQs 22.3 22.5)

22.1  The difference between treatment and cure in HIV/AIDS

Knowing the difference between treatment and cure is quite important in providing care to patients with chronic illnesses like HIV/AIDS. Treatment is the application of a medicine or a remedy to relieve symptoms and/or signs of an illness; in the context of a communicable disease like HIV/AIDS, it doesn’t necessarily mean getting rid of the infectious agent from the patient’s body.

On the other hand, cure means eradication of the cause of the illness — the complete removal of the pathogen from the body; for example, there is a cure for malaria or tuberculosis, but not yet for HIV.

You need to understand that antiretroviral therapy for HIV does not cure HIV, because it cannot eradicate the virus from the body. Even though effective treatments to control HIV exist now, there is still no cure. It is important that you make sure all the PLHIV in your care also understand this, for the following reasons:

  • HIV treatment is for life: It will be easier for PLHIV to understand that, because it is not curative, HIV treatment will be for the rest of their lives, and they must continue taking the drugs even though they may have adverse side-effects (which will be covered later in this study session).
  • Drug resistance: You will be better placed to explain to PLHIV that if treatment is interrupted, HIV may become drug resistant, that is, the virus in their bodies will not respond to treatment in future because the virus is no longer susceptible to the drugs. If this happens, it will be necessary to use other drugs that may not be as effective in keeping the virus levels in the blood down, or that may have more side-effects (drug resistance will be referred to again later in this study session).
  • Minimising risk of transmission: Since there is still no vaccine to prevent HIV, you will need to educate and discuss prevention strategies with PLHIV consistently. They must understand that they are still able to transmit HIV to a healthy uninfected person, even if they feel healthier because they are on ART.

You will learn more about prevention of HIV transmission for PLHIV in Study Session 26.

22.2  The benefits of ART

The benefits of ART can be divided into three — benefits to PLHIV, benefits to the health service, and benefits to the community at large, as described below.

Benefits of ART to the patient:

  • Prolongs life and improves quality of life.
  • Decreased stigma surrounding HIV infection, since treatment is now available.
  • Households can stay intact, because patients survive for so much longer.
  • Businesses and jobs can stay intact for the same reason.
  • Reduces mother-to-child transmission of HIV.
  • Less money is spent on treating opportunistic infections and providing palliative care (end-of-life care).

Benefits of ART to the health service:

  • Increased number of people who accept HIV testing and counselling, because treatment is available.
  • Increased motivation of health workers, since they feel they can do more for PLHIV.

Benefits of ART to the community:

  • Decreased number of orphans.
  • Increased awareness of HIV in the community, since more people accept HIV counselling and testing.

22.3  Antiretroviral drugs (ARVs) and antiretroviral therapy (ART)

In Study Session 20, you learnt that HIV is a virus. In fact, there are many types of viruses. The classification of viruses is very complex, and explaining it here would go beyond the scope of this study session. For your work as a Health Extension Practitioner, you only need to know that HIV is a type of virus that is termed a retrovirus. Hence, drugs that are used to treat HIV infection are called antiretroviral drugs, which can be shortened to ARVs.

Antiretroviral therapy (HIV treatment), also known as ART, is a treatment that uses ARV drugs. The two main goals of ART are:

  1. to reduce the number of viruses in the patient’s blood to a very low level
  2. to increase the number of CD4 lymphocytes in the patient as much as possible, to increase the body’s immunity to infection, including immunity against HIV.

Lymphocytes are a type of white blood cell involved in the immune system; CD4 lymphocytes (or CD4 cells) are a specialised type of lymphocyte, which stimulate all the other defensive mechanisms in the immune system. For this reason, they are sometimes also called ‘helper T cells’.

Remember from Section 20.2 that once inside the body, HIV first infects a previously uninfected CD4 lymphocyte. Then the HIV-infected CD4 lymphocyte produces many copies of the virus that are released into the blood to infect other CD4 lymphocytes, and so the process goes on, again and again. The ARV drugs work to stop this cycle by acting at different stages of the process.

22.3.1  Groups of ARV drugs

There are three big groups of ARV drugs available in Ethiopia, as listed below:

  1. The NRTI drugs: this stands for ‘Nucleoside and Nucleotide Reverse Transcriptase Inhibitors’ (divided into NsRTIs and NtRTIs).
  2. The NNRTI drugs: this stands for ‘Non-Nucleoside Reverse Transcriptase Inhibitors’.
  3. The PI drugs: this stands for ‘Protease Inhibitors’.

Note that you don’t need to know the complex mechanisms of action of these drugs. Likewise, you don’t need to memorise the names of the drug groups.

Table 22.1 lists the commonly used ARV drugs in Ethiopia, arranged into the various groups, together with some rarely used drugs. But be aware that the table is not a complete list of all the ARV drugs; for example, it does not include all the rare drugs, or drugs that are not yet available in most resource-constrained settings like Ethiopia. You can use Table 22.1 as a reference in case a patient asks you about a specific drug, but remember to refer him or her to a health centre for more detailed advice than you can give at health post level. The drugs listed in the first three columns of Table 22.1 are the ones most widely used in Ethiopia, and we will say more about them later in this study session (Sections 22.3.3 and 22.4).

Table 22.1  Commonly used antiretroviral drugs (with their common abbreviations).
Nucleoside reverse transcriptase inhibitors (NsRTI)Nucleotide reverse transcriptase inhibitors (NtRTI)Non-nucleoside reverse transcriptase inhibitors (NNRTI)Protease inhibitors (PI)

Stavudine (d4T)

Lamivudine (3TC)

Zidovudine (AZT or ZDV)

Didanosine (ddI)

Abacavir (ABC)

Tenofovir disoproxil fumarate (TDF)

Nevirapine (NVP)

Efavirenz (EFV)

Lopinavir (LPV)

Ritonavir (RTV)

Atazanavir(ATV)

Note that you do not need to memorise the different classes and names of the drugs in Table 22.1

22.3.2  Why is the combination of three antiretroviral drugs necessary?

Combination therapy, in the context of HIV/AIDS, means prescribing three or more ARV drugs to be taken together. Combination therapy is useful for many reasons. Here are the most important ones.

Three or more drugs are needed to stop HIV

Remember that HIV makes new copies of itself very rapidly in infected CD4 lymphocytes. Given time, HIV infection/production escalates out of control, and eventually will result in high levels of viruses in the blood, and low levels of CD4 lymphocytes.

  • What are the consequences of this for PLHIV?

  • They are very likely to develop the opportunistic infections described in Study Session 21.

One drug, by itself, can slow down this fast rate of HIV infection and/or production. Two drugs acting at different points of the virus production cycle can slow it down more, and three drugs together have a very powerful effect. Since ARVs from different drug groups attack the virus in different ways, the standard combination in ART is to use three different ARV drugs.

Combining ARV drugs may overcome or delay drug resistance

Viruses, like bacteria, quickly adapt to their environment, so they can carry on multiplying even when the conditions change for the worse. When a person living with HIV is given ARV drugs for the first time, the environment (in this case, the human body), surrounding the billions of viruses, changes so that it is more difficult for the viruses to multiply. HIV quickly adapts to this new environment by changing its structure in ways that make ARV drugs less effective. The result of this process is that it can go on multiplying even when the drugs are present — this is called drug resistance.

HIV has to make only a single, small change to its structure in order to resist the effects of a particular group of ARV drugs. However, if drugs from more than one group are given in combination, HIV has to make several different changes in its structure in order to resist them all.

It takes longer for HIV to make all the changes necessary for resistance to develop to two drugs, and when three drugs are given together, it takes even longer. This means that giving a combination of three drugs will remain effective in treating HIV infection for a longer period of time than giving just a single drug (or even two).

Note that HIV/AIDS treatment programmes do not randomly prescribe any three ARV drugs. There are strict national guidelines on how to prescribe the different ARV drugs in standard combinations in Ethiopia, as in other countries, as you will see below.

22.3.3  How are antiretroviral drugs combined?

A prescribed or recommended collection of medications intended to treat a disease is called a treatment regimen (or simply a regimen). The regimens used in ART can be first line, second line, or even third line.

First-line regimens

A first-line regimen is a combination of drugs that will be given to an HIV-positive patient who has never taken any ARV drugs before. Most commonly, a first-line regimen will consist of two NsRTIs and one NNRTI.

Box 22.1 lists the most common first-line regimens used in Ethiopia at the present time (2010).

The full names of the drugs in Box 22.1 can be found from their abbreviations by looking back at Table 22.1.

Box 22.1  Common first-line drug regimens for ART

                       AZT-3TC-NVP

                       AZT-3TC-EFV

                       d4T-3TC-NVP

                       d4T-3TC-EFV

                       TDF-3TC-EFV

                       TDF-3TC-NVP

Note that 3TC is included in all of the first-line regimens in Box 22.1 (always listed in the middle of the three drugs). Some drugs are not used together in the same regimen. Note that d4T and AZT are not used together, and NVP and EFV are not used together.

Second- and third-line regimens

Many patients on ART will eventually develop failure of therapy, which means the first-line regimen will not be effective anymore. This is often because the drugs were not taken correctly, and this allowed HIV to become resistant to them. In that case, the doctor may decide to switch to a second-line regimen, which is more expensive. Usually, the second-line regimen will consist of two NRTIs and one PI drug in combination. The second-line regimen is stronger, but there are more pills to take, and this regimen sometimes has food restrictions and more side-effects. Even a second-line regimen can fail, if not taken consistently and correctly, so a third-line regimen may have to be used.

Note that if ART is interrupted, the virus levels in the patient’s blood will increase, and the numbers of CD4 lymphocytes will slowly decrease, until finally the health of the patient will deteriorate. Therefore, making sure that ART is continuously maintained, or in other words, that the patient maintains the adherence to the treatment, is extremely important.

First-line drug regimens and fixed-dose combinations

First-line ARVs (Box 22.1) are mainly given twice a day. But there are some drugs which are given once a day, like Efavirenz (EFV) and Tenofovir disoproxil fumarate (TDF). Note that Abacavir (ABC) and TDF can also be used as first-line ARV drugs. According to the current Ethiopian ART guidelines, new adult and adolescent patients are not started on a d4T-containing regimen; instead they are prescribed AZT or TDF-containing regimens.

First-line drug regimens commonly include ARVs in fixed dose combinations, meaning combinations of three ARV drugs in fixed doses in the same tablet (e.g. AZT + 3TC + NVP in one tablet, see Figure 22.1a); this is taken twice a day (every 12 hours) except in the first two weeks of ART. There are also fixed drug combinations which contain two drugs in one tablet (e.g. AZT + 3TC), which is given with a third drug separately (e.g. Efavirenz or EFV, see Figure 22.1 b) in a different tablet.

Antiretroviral drugs.
Figure 22.1  Antiretroviral drugs: (a) A fixed-dose combination of Lamivudine (3TC), with Zidovudine (AZT or ZDV) and Nevirapine (NVP) in single tablets. (b) A single drug, Efavirenz (EFV), which may be taken in addition to other ARV drugs. (Photos: Basiro Davey)

22.4  ARV side-effects and how to manage them

Every drug can have side-effects, which means unwanted effects that result when taking the drug for treatment. ARV drugs can have multiple side-effects, some of which are common, and others which are rare. The most common side-effects of ARV drugs are shown in Table 22.2. You may need to advise patients when some of these occur, or refer them to a nearby health centre or hospital if serious side-effects arise.

Table 22.2  The most common side-effects of ARV drugs used in the first-line regimen.

Very common side-effects Potentially serious side-effectsSide-effects occurring later during treatment
ARV drug

Counsel patients about these and suggest ways they can manage them; also be prepared to help manage them when patients seek care at home.

Warn patients, and tell them to seek care urgently (or refer them urgently) if these occur.

Advise patients to seek care at a health centre or hospital.

Stavudine (d4T)
  • Nausea (the sensation of having an urge to vomit)
  • Diarrhoea
Refer urgently:
  • Severe abdominal pain;
  • Fatigue and shortness of breath.
Changes in fat distribution of the body:
  • Arms, legs, buttocks, cheeks become thin;
  • Breasts, belly, back of neck become fat.
Refer as soon as possible:
  • Tingling (a sensation of prickling), numbness (unable to feel, or loss of sensations), or painful feet, legs or hands.
Lamivudine (3TC)
  • Nausea
  • Diarrhoea.
Nevirapine (NVP)
  • Nausea
  • Diarrhoea.
Refer urgently:
  • Yellow eyes
  • Skin rash
  • Fatigue and shortness of breath
  • Fever.
Zidovudine (AZT or ZDV)
  • Nausea
  • Diarrhoea
  • Headache
  • Fatigue (a feeling of tiredness, or lack of energy)
  • Muscle pain.
Refer urgently:
  • Pallor (anaemia).
Efavirenz (EFV)
  • Nausea
  • Diarrhoea
  • Strange dreams
  • Difficulty sleeping
  • Memory problems
  • Headache
  • Dizziness (light-headed, feeling faint, unsteady, loss of balance).
Refer urgently:
  • Yellow eyes
  • Psychosis or confusion (Psychosis involves loss of contact with reality, usually with false beliefs about what is taking place or one’s own identity (delusions), and seeing or hearing things that aren't there (hallucinations). It is discussed in detail in the Module on Non-Communicable Diseases, Emergency Care and Mental Health).
  • Skin rash.

Note that side-effects such as nausea, vomiting and diarrhoea are very common with many ARV drugs, especially in the first 2–3 weeks of treatment. If a patient has nausea, you should advise him/her to take the tablets with food (or just after eating food). Patients who develop diarrhoea should be advised to drink more fluids, including oral rehydration salts, eat small and frequent meals, and avoid spicy foods. If the nausea, vomiting or diarrhoea worsens, the patient should be referred to a health centre or hospital as soon as possible.

Summary of Study Session 22

In Study Session 22, you have learned that:

  1. Antiretroviral therapy (ART) means giving antiretroviral (ARV) drugs to people who are HIV-positive to reduce the level of viruses in their bodies and increase the number of CD4 lymphocytes.
  2. There are three big groups of ARVs (NRTIs, NNRTIs and PIs).
  3. The standard regimen in ART is to give a combination of three different ARV drugs for maximum possible treatment effect, and to overcome or delay the development of drug resistance by HIV. Prescribing only one ARV drug increases the risk of resistance developing quickly to that drug.
  4. ART has many benefits, including improving the quality of life for patients, decreasing stigma and discrimination, prevention of transmission of the virus from mother to child, and increasing uptake of other HIV services, like counselling and testing.
  5. First-line drug regimens are given to patients who have never taken ARV drugs previously. If these combinations fail, or the patient experiences severe side effects, different second-line or even third-line drug combinations can be prescribed, but these are more expensive and may be less effective.
  6. The most common side-effects of ARV drugs are nausea, vomiting, diarrhoea and headaches, especially in the first few weeks of ART. Examples of serious side effects which require urgent referral are severe abdominal pain, fever, yellow eyes, tingling and numbness, fatigue with shortness of breath, yellow eyes, pallor (anaemia) and skin rash.

Self-Assessment Questions (SAQs) for Study Session 22

Now that you have completed this study session, you can assess how well you have achieved its Learning Outcomes by answering the following questions. Write your answers in your Study Diary and discuss them with your Tutor at the next Study Support Meeting. You can check your answers with the Notes on the Self-Assessment Questions (SAQs) at the end of this Module.

SAQ 22.1 (tests Learning Outcomes 22.1 and 22.2)

Is the following statement true or false? Explain your answer.

‘There are effective ARVs to treat HIV, and a vaccine which cures HIV/AIDS. But these treatments are not available in Ethiopia.’

Answer

The statement is false. Even though effective treatments to control HIV exist now, there is still no cure for HIV/AIDS anywhere in the world, and no vaccine to prevent it.

SAQ 22.2 (tests Learning Outcomes 22.1, 22.2 and 22.3)

Which of the following statements is true? For each false statement, explain what is incorrect.

A  ART can completely eliminate HIV from the human body.

B  The two main goals of ART are to reduce the number of CD4 cells, and eradicate the virus from the blood.

C  Two ARV drugs are combined in the most effective treatment for HIV.

D  All of the above statements are false.

Answer

The answer is (D). All of the statements are false because:

A  ART cannot completely eliminate HIV from the human body.

B  The two main goals of ART are to reduce the number of viruses in the blood to a very low level (they cannot be eradicated by current treatments), and to increase the number of CD4 lymphocytes as much as possible, to boost immunity.

C  Combining only two ARV drugs is less effective than treating HIV with a combination of three ARV drugs from different groups.

SAQ 22.3 (tests Learning Outcomes 22.3 and 22.4)

Explain why a combination of three ARV drugs will be more effective at stopping the multiplication of HIV in the human body than two drugs, or one alone.

Answer

One ARV drug can slow down the fast rate of new HIV production in the body, but two drugs acting at different points of the multiplication cycle can slow it further, and three drugs together have an even more powerful effect. This is because ARV drugs from different drug groups attack the virus in different ways. HIV would have to make several different changes in its structure in order to develop resistance to all three drugs.

SAQ 22.4 (tests Learning Outcome 22.2)

Is the following statement true or false? Explain your answer.

‘One of the major benefits of ART is to make the patient feel healthy and to enable him or her to practise unsafe sex, because the treatment stops HIV from being passed on.’

Answer

That is absolutely wrong! HIV can still be transmitted from a person on ART to an uninfected sexual partner if they practise unsafe sex. Remember that ART does not cure HIV/AIDS.

First read Case Study 22.1, and then answer the question that follows it.

Case Study 22.1  Abebech’s story

Abebech is a 47-year-old female who is HIV-positive and living in your village. She started on ART two weeks ago at a nearby health centre. While conducting a household visit you find that she has nausea and has been vomiting one or two times per day since the start of ART. The vomiting occurs several hours after eating. Upon checking her medication you learn that she is taking AZT + 3TC + EFV. She can eat food, and has no fatigue.

SAQ 22.5 (tests Learning Outcome 22.4)

What advice should you give to Abebech, and why?

Answer

First, start by reassuring Abebech that nausea and vomiting are common side-effects of most ARV drugs, especially in the early weeks of treatment. Then advise her to take the drugs with food, and drink plenty of fluids. Tell her that if the vomiting worsens, she should go back to the health centre for further assessment and management.