All pregnant women in the Netherlands have been tested for HIV since 2004. If they have the virus, they are given medication. Children of HIV-infected mothers are given HIV inhibitors as soon as possible after birth. The medication must be administered for four weeks to reduce the chance of HIV transmission to less than one percent.
If you have had HIV since you were born, your mother probably did not know that she had HIV. Otherwise she would have taken medication to ensure that the virus would not be transmitted to you.
Fortunately, everyone in the Netherlands with an HIV infection is treated with anti-HIV drugs. Therefore no one develops AIDS anymore in the Netherlands.
There are different types of HIV inhibitors, which all work in their own way. For instance, there are drugs that prevent the HIV particle from entering the CD4 cell. Other drugs ensure that the virus cannot replicate itself further. They all combat the virus in different ways but have the same end result: fewer virus particles in the blood. The best results are achieved if you combine these drugs. We call this combination therapy cART (combination antiretroviral therapy). There are six different types (groups) of HIV inhibitors, but four of these are used most frequently. If you would like to know more, you can watch the added videos, which explain how these different HIV inhibitors work.
Combination drugs
One pill can contain several HIV inhibitors that all work differently. This means that you do not have to take as many pills but you still get all the medication. Another advantage is that combining the drugs also enhances their effect. Multiple combinations are possible.
Which drugs will you be given?
In the Netherlands, the treatment and guidance for children with an HIV infection is very well regulated. There are specialized treatment centers (in four university hospitals in Amsterdam, Rotterdam, Utrecht and Groningen) and, in principle, all drugs are available. Which drugs you are given and when depends on your age, your weight, the number of CD4 cells and the symptoms that you have. How you are feeling is, however, also important. The treatment you receive is tailored to you. The guidelines of organizations such as the WHO (World Health Organization, an international organization that deals with healthcare) are followed as far as possible. These guidelines are adapted regularly in line with the latest developments.
Therapy compliance
Taking HIV medication is no small feat. Anyone who has been taking it for a long time knows how difficult it is sometimes. You constantly have to think about your pills because you have to take them exactly on time. You have to take them with you if you go out, store them in the correct way and remember to ask your doctor in time for a new prescription. And you have to do all this your whole life. Some children find taking medication annoying, because they do not feel unwell at all, or because they just get fed up of the medication. If you are having difficulties, it can be good to talk to someone about it. Together with your pediatrician or HIV consultant, you can then look for possible solutions or tricks to make it easier for you. Because it is very important to continue taking your medication!
If you take it incorrectly, irregularly or not at all, the HIV virus can start to replicate itself again, leading to mutations (incorrect copies), which will mean that the medication will no longer be effective. The virus has become insensitive to the medication, this is called resistance. In the event of resistance, you have to switch to a different combination of medications to keep the virus under control. But please, be aware that you can only switch to a different combination a small number of times. Taking your medication regularly is therefore very important. It is the only way to prevent your immune system from weakening (deteriorating), which is what makes you sick.
Medications to prevent infections
If you have very few CD4 cells, it means that you are susceptible to infections. A low dose of antibiotics can be prescribed for a longer period of time, to prevent bacterial infections.
All pregnant women in the Netherlands have been tested for HIV since 2004. If they have the virus, they are given medication. Children of HIV-infected mothers are given HIV inhibitors as soon as possible after birth. The medication must be administered for four weeks to reduce the chance of HIV transmission to less than one percent.
If you have had HIV since you were born, your mother probably did not know that she had HIV. Otherwise she would have taken medication to ensure that you did not contract the virus.
Fortunately, everyone in the Netherlands with an HIV infection is treated with anti-HIV drugs. Therefore no one develops AIDS anymore in the Netherlands.
There are different types of HIV inhibitors, which all work in their own way. They all combat the virus in different ways but have the same end result: fewer virus particles in the blood. The best results are achieved if you take these drugs all at the same time. We call this combination therapy cART (combination antiretroviral therapy).
The permanent elimination of the HIV virus, i.e. a cure, is not yet possible. You will therefore have to take HIV inhibitors all your life. Unfortunately, long-term use of these drugs also has negative side effects. Researchers are working hard to find solutions to this and on developing drugs to cure HIV.
WHO guideline
The World Health Organization (WHO) is active worldwide in the diagnosis and treatment of HIV and the prevention of new infections. In 2013, the WHO guideline for antiretroviral therapy (cART) was revised. The treatment of HIV in the Netherlands has been aligned with this latest guideline.
Antiretroviral drugs
A combination of different drugs is used in the treatment of HIV. This is known as combination therapy or combination antiretroviral therapy (cART). The drugs all work differently and each affects the virus in different ways and at different times. They therefore reinforce each other's effect so as to combat the virus as effectively as possible.
Although the drugs have different functions, they all have the same goal: to ensure that the HIV particles cannot replicate themselves. This ensures that no new CD4 cells will be infected and that the number of CD4 cells will not continue to decrease. Since new CD4 cells are constantly being made in our bone marrow, the number of CD4 cells can even increase again with effective therapy.
HIV inhibitors can be divided into four groups based on their function:
1. Drugs that prevent HIV from fusing with a CD4 cell, entry inhibitors
2. Drugs that inhibit the activity of reverse transcriptase
3. Drugs that inhibit the activity of integrase
4. Drugs that inhibit the activity of protease
The viral enzymes reverse transcriptase, integrase and protease are indispensable for the replication of the virus. They trigger certain steps and ensure that one step follows the other, eventually creating new virus particles.
Entry inhibitors (not given to children)
Entry inhibitors are drugs that prevent an HIV particle from fusing with a CD4 cell by binding with one of the envelope proteins or an auxiliary receptor. This means that the virus particle cannot enter the cell and therefore
cannot introduce its viral RNA into the CD4 cell in order to replicate itself.
Examples of entry inhibitors: enfuvirtide (T20, Fuzeon®) and maraviroc (Selzentry®).
Reverse-transcriptase inhibitors
Reverse transcriptase copies the genetic material of the virus and helps to make new virus particles. It ensures that single-stranded viral RNA is converted into double-stranded complementary DNA. This viral DNA can be integrated into the DNA of the CD4 cell, where it can continue to replicate itself. A reverse-transcriptase inhibitor (RTI) ensures that the viral RNA cannot be converted into viral DNA. The replication of the virus stops.
There are several types of reverse-transcriptase inhibitors: nucleoside (NRTI), nucleoside-analog (NARTI) and non-nucleoside RTI (NNRTI). The first two ensure that they become integrated in the viral DNA strand, as a result of which the DNA cannot extend further. The formation of the DNA chains is stopped and the virus does not continue to replicate itself. A non-nucleoside RTI binds to reverse transcriptase, meaning that no more viral DNA can be formed and the virus cannot replicate further.
Examples of NRTIs:
- abacavir (ABC, Ziagen®)
- abacavir/lamivudine (ABC/3TC, Kivexa®)
- abacavir/lamivudine/zidovudine (ABC/3TC/ZDV, Trizivir®)
- didanosine (ddl, Videx® and ddl EC, Videx EC®)
- emtricitabine (FTC, Emtriva®)
- emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, Truvada®)
- lamivudine (3TC, Epivir®)
- lamivudine/zidovudine (3TC/ZDV, Combivir®)
- tenofovir disoproxil fumarate (TDF, Viread®)
- zidovudine (AZT or ZDV, Retrovir®)
Examples of NNRTIs:
- efavirenz (EFV, Stocrin®)
- nevirapine (NVP, Viramune XR®, Viramune®)
- rilpivirine (RPV, Edurant®), not registered for use in children
Integrase inhibitors (not yet given to children in the Netherlands)
Integrase ensures that the viral DNA enters the nucleus of the CD4 cell and that it is integrated into the DNA of the CD4 cell. An integrase inhibitor (II) binds to integrase and ensures that the viral DNA cannot integrate itself in the CD4 cell. This prevents the virus from replicating itself.
Examples of integrase inhibitors:
- dolutegravir (DTG, Tivicay®)
- raltegravir (RAL, Isentress®)
Protease inhibitors
Protease makes sure that viral amino acid chains are cut into small pieces. The proteins and enzymes that are produced in this way play an important role in the maturation of HIV and the extent to which the virus is infectious. Protease inhibitors (PI) ensure that HIV cannot develop further. The virus particles created remain incomplete and are unable to work well.
Examples of protease inhibitors:
- atazanavir (ATV, Reyataz®)
- darunavir (DRV, Prezista®), not in children under the age of three
- lopinavir/ritonavir (LPV/RTV, LPV/r, Kaletra®)
- ritonavir (RTV, Norvir®)
Combination drugs
One pill or capsule can contain several drugs that all work differently. The benefit of this is that you do not need to take as many pills but still get all the medication. It also reduces the chance of you forgetting or missing out pills. Another advantage is that combining the drugs also enhances their effect. Multiple combinations are possible.
Combination drugs with NRTI + NNRTI:
- efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF, Atripla®)
- emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF, Complera®), not registered for use in children
Combination drugs with more than one NRTI:
- lamivudine/zidovudine (3TC/ZDV, Combivir®)
- emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, Truvada®)
Combination drug with more than one protease inhibitor:
- lopinavir/ritonavir (LPV/RTV, LPV/r, Kaletra®)
Combination drug with NRTI + integrase inhibitor + drug that improves the effect of the integrase inhibitor (inhibits liver enzymes to delay integrase inhibitor breakdown):
- elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (QUAD, Stribild®), not yet registered for use in children.
Schematic overview of types of antiretroviral drugs
Entry inhibitor (not given to children)
| What does it do? | It prevents the fusion of HIV and CD4 cells by binding to an envelope protein. |
| Examples | enfuvirtide (T20, Fuzeon®). |
| What does it do? | The drug binds to CCR5, therefore preventing the fusion of HIV and CD4 cells. |
| Examples | maraviroc (Selzentry®). |
Reverse-transcriptase inhibitor (RTI)
| What does it do? | It prevents further replication of the virus.
An NRTI allows itself to be integrated into the DNA strand, after which further extension stops, thereby stopping the replication. |
| Examples | abacavir (ABC, Ziagen®)
abacavir/lamivudine (ABC/3TC, Epzicom®),
abacavir/lamivudine/zidovudine (ABC/3TC/ZDV, Trizivir®),
didanosine (ddl, Videx® and ddl EC, Videx EC®),
emtricitabine (FTC, Emtriva®),
emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, Truvada®),
lamivudine (3TC, Epivir®),
lamivudine/zidovudine (3TC/ZDV, Combivir®),
tenofovir disoproxil fumarate (TDF, Viread®),
zidovudine (AZT or ZDV, Retrovir®) |
- Non-nucleoside RTI (NNRTI)
| What does it do? | It prevents further replication of the virus.
An NNRTI binds to reverse transcriptase so that it can no longer do its job and the formation of DNA strands stops. |
| Examples | efavirenz (EFV, Sustiva®, Stocrin®),
nevirapine (NVP, Viramune XR®, Viramune®),
rilpivirine (RPV, Edurant®). |
- Integrase inhibitor (not yet given to children)
| What does it do? | It prevents further replication of the virus.
An integrase inhibitor binds to integrase and blocks the integration of viral DNA in the CD4 cell. |
| Examples | dolutegravir (DTG, Tivicay®), raltegravir (RAL, Isentress®). |
| What does it do? | It blocks the final development of an HIV particle. |
| Examples | atazanavir (ATV, Reyataz®),
darunavir (DRV, Prezista®),
fosamprenavir (FPV, Lexiva®),
indinavir (IDV, Crixivan®),
lopinavir/ritonavir (LPV/RTV, LPV/r, Kaletra®),
nelfinavir (NFV, Viracept®),
ritonavir (RTV, Norvir®),
saquinavir (SQV, Invirase®),
tipranavir (TPV, Aptivus®). |
Which drugs will you be given?
In the Netherlands, the treatment and guidance for children with HIV is very well regulated. There are specialized treatment centers (in four university hospitals in Amsterdam, Rotterdam, Utrecht and Groningen) and, in principle, all drugs are available.
Which drugs you are given and when depends on your age, your weight, the number of CD4 cells and how many symptoms you have. However, your family situation and psychological state are also important. The treatment you receive is tailored to you and the guidelines from the WHO (World Health Organization) are followed as far as possible. These guidelines are adapted regularly in line with the latest developments.
The WHO HIV guideline recommends starting cART in all children under the age of five and in all pregnant women, regardless of the number of CD4 cells and the phase of HIV. In children between the ages of five and ten, it is recommended to start treatment if the number of CD4 cells is below 500 cells/mm3, regardless of the phase of HIV. From around the age of ten, it is recommended to start treatment if the number of CD4 cells is below 500 cells/mm3, regardless of the phase of HIV, or in the event of complaints and symptoms consistent with an advanced, serious phase of HIV. If there are additional diseases, such as tuberculosis or hepatitis B, it is recommended that treatment will be started in all cases, regardless of the number of CD4 cells or the phase of HIV.
Therapy compliance
Taking HIV medication is no small feat. Anyone who has been taking it for a long time knows how difficult it is sometimes. You always have to bear it in mind because it is important to take your tablets exactly on time. You have to take them with you if you go out, store them in the correct way and remember to order them from the pharmacy. And you have to do all this your whole life. Some children find taking medication annoying, because they do not feel unwell, or because they just get fed up of the medication. If you are having difficulties with it, it can be good to talk to someone about it. Together with your doctor or HIV consultant, you can then look for possible solutions or tricks.
It is very important to continue taking your medication correctly! If you take it incorrectly, irregularly or not at all, the HIV virus can start to replicate itself again, causing mutations, which will mean that the medication will no longer be effective. The virus particles then become insensitive to your medication. This is called resistance. In the event of resistance, you have to switch to a different combination of medications. However, it is important to note that you can only switch to a different combination a small number of times. Taking your medication regularly is therefore very important. It is the only way to prevent your immune system from deteriorating, which is what makes you sick.
Medication to prevent infection after contact with HIV
If you have had unprotected sexual contact or a needlestick injury when the other person is seropositive, consult an HIV specialist as soon as possible. If you do not have an HIV infection yourself, you can get post-exposure prophylaxis (PEP). This is a treatment with antiretroviral drugs. If you start these right away, an HIV infection can be prevented. You must start within 72 hours of the contact, however, preferably within the first few hours. Blood should also be taken at various points to see whether you have contracted an HIV infection. You must use PEP until the result is final. The treatment therefore takes a few weeks. Because the treatment also has negative side effects, the risk must be properly assessed. This means that you have to think carefully before you start taking PEP.
Research is also being carried out on taking medication before unprotected sexual contact with someone who is seropositive – this is called pre-exposure prophylaxis (PrEP) – in order to reduce the risk of infection for the seronegative partner. The effectiveness and safety of this treatment is still under investigation, therefore it is not yet a standard treatment.
Other medications
There are also medications for symptoms caused by infections or side effects of the cART. These include antibiotics in the event of a bacterial infection or medication that protects the stomach wall or prevents nausea.
Medications to prevent infections
If you have very few CD4 cells, you can easily contract opportunistic infections. You can try to prevent an infection caused by bacteria by using prophylaxis. Prophylaxis is a low dose of antibiotics taken over a longer period.
