Standard treatment for HIV is a combination of 3 different drugs that stop 2 or more very important stages within the HIV lifecycle which are vital for the virus to make more copies of itself by using cellular processes of CD4 cells. Within days of starting treatment the drugs get to work, and the viral load is significantly reduced. This takes pressure off the immune system and we see CD4 cell count start to increase which is a sign the immune system is recovering and getting on with the day job.
There are different families or classes of drugs that work at different points within the HIV life cycle:
Nucleoside Reverse Transcriptase Inhibitors (NRTI’s) block one of the HIV enzymes (reverse transcriptase) which copies (transcribes) the single strand of HIV genetic material (RNA) into a double strand of genetic material (DNA). The transcription process enables HIV to use CD4 cell processes to make more copies of itself.Two drugs from the NRTI group are combined together to form what is often called the backbone regimen, comprising of the following paired drugs:
Emtricitabine / tenofovir
Lamivudine / abacavir
Note: The paired NRTI drugs are usually formulated into a single pill (Truvada as an example) or can also form part of a complete combination pill (Triumeq as an example).
Any of the drugs listed below can be added to the NRTI backbone regimen to form a standard 3-drug combination:
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI’s) interfere with the enzyme (reverse transcriptase) HIV uses in the copying or transcription process. Drugs from the NNRTI family stop the copying this process in a slightly different way to NRTI’s and provide another method of preventing HIV making copies of its RNA into DNA. Frequently used NNRTI drugs include:
Doravirine (awaiting EU and NHS approval)
Integrase Transfer Strand Inhibitors (INST’s)prevent HIV DNA being transported and inserted into human DNA located in the nucleus of the CD4 cells. It is this part of the lifecycle that effectively turn CD4 cells into viral factories when they become activated. When activated, the cell nucleus instructs the cell processes to produce new HIV proteins and other HIV components that are needed to assemble new copies of the virus. Frequently used INSTI’s include:
Elvitegravir (boosted with cobicistat)
Protease Inhibitors (PI’s) prevent HIV proteins and other genetic components being cut (cleaved) into functional components needed to produce more copies of HIV. Protease inhibitors get to work when newly created HIV proteins are transported to the CD4 cell surface membrane. Protease inhibitors continue to work once immature HIV is released from the CD4 cell, a process known as budding. Without the essential functional viral components HIV is unable to fully mature and go on to infect other CD4 cells. Frequently used PI’s include:
Drugs in the protease inhibitor group are used with a boosting agent such as cobicistat or sometimes low dose ritonavir so they remain at effective levels in the body.
Entry inhibitors prevent HIV entering the CD4 cell, hijacking cell processes which essentially turns the CD4 cell into a viral factory. Entry inhibitors are rarely used in standard treatment combinations. The entry inhibitor maraviroc blocks one of the co-receptors located on the surface of the CD4 cell that HIV uses to enter the cell. Entry inhibitors tend to be used where there is resistance to one or more of the drugs in a particular combination.
Animation showing the HIV lifecycle in detail
It is now recommended to start treatment as soon as possible after diagnosis, regardless of CD4 cell count. The START study has shown there can be longer term health benefits of starting treatment even where CD4 levels are within the normal expected range for someone who doesn’t have HIV.
The primary aim of HIV treatment is to reduce the levels of HIV (viral load) in the blood and other bodily fluids so the virus cannot be detected using a standard viral load test (less than 50 copies per ml). Once the viral load becomes undetectable, CD4 cell count increases, which means the immune system is better able to protect the body from harmful bacterial, viral, fungal and parasitic infections. Detailed below are some of the important points the impact treatment has on viral load, CD4 cell count and our overall health and wellbeing.
- Treatment stops active CD4 cells that contain HIV genetic material (DNA) from making more copies of itself. This means viral load is significantly reduced within the first few days and weeks of starting treatment. As viral load drops people often find they have more energy and generally feel better.
- We expect viral load to reduce by a factor of 10 (or more) in the first 4 weeks of treatment (as an example, 50,000 down to 5,000 or less) and then continue to get lower over the next few months until it reaches the point where it is no longer detectable in the blood less than 50 copies using a standard viral load test. Some clinics now use tests that have cut off points at less than 40 or even 20 copies.
- Most people become undetectable between 1 and 3 months of starting treatment. The time taken can depend on the choice of drugs and viral load prior to starting treatment. Combinations that contain an integrase inhibitor reduce viral load very quickly, which can be an important consideration in some cases. Reaching undetectable levels can provide a big emotional boost and is a significant milestone in our journey with HIV.
- Starting treatment with a viral load above 100,000 copies may mean it will take longer than 3 months to get to undetectable levels, and your Dr and clinic team will monitor your progress closely. Some treatment options aren’t recommended for use where viral load is higher than 100,000 before starting treatment. This isn’t anything to be worried about, it just means your Dr will take this into account when talking to you about your treatment options.
- When viral load becomes undetectable the immune system is able to recover and become stronger. The balance between CD4 cells and other immune cells starts to normalise, and the immune system as a whole stands down from being at high levels of activation. This improve the overall functioning of the immune system and we see a return to health in the wider sense. Many people feel much better in themselves, notice they have more energy, regain lost weight and find many minor symptoms start to clear up over time once they have started treatment.
- Treatment doesn’t have a direct effect on the CD4 count. In any given day many CD4 cells become worn out and die and new ones are produced. This cell turnover is a natural process and when left untreated HIV disrupts this process. The increases seen as a result of HIV being undetectable means the natural balance in immune cells is restored as is the protective effect on the immune system and our health in general.
- CD4 count usually increases slowly and steadily over time. The biggest rise can often occur during the first 3 to 12 months after starting treatment. This can continue into a second year although increases may be much smaller. Sometimes it can take a little longer for CD4 cell counts to get into the expected normal range, which is between 400 to 1600.
- The way HIV interacts with the immune system is very individual, and none of us usually know what our CD4 cell count was before HIV came along. Setting a target for your CD4 cell count or compare results with others maybe not be helpful, as we all have a unique response to HIV and its treatment. The important thing is to remain undetectable which is the only way we can influence CD4 cell count and a return to normal immune function in the long term.
- Once you and your Dr are happy your treatment is working well, you’re not experiencing any ongoing side effects, and everything has settled down, you won’t have to visit your clinic as frequently. People who are stable on treatment only tend to visit their clinic every six months for routine monitoring and Dr’s appointments. If you’d prefer to be seen more regularly do discuss this with your Dr and clinic team.
Taking treatment as directed by your Dr or Pharmacist is referred to as adherence. For treatment to be fully effective it is important that drug levels in the body are high enough to ensure HIV remains at undetectable levels. Maintaining daily adherence means it is extremely unlikely the virus will become more active and rise to detectable levels. Remaining undetectable prevents the virus becoming resistant to one or more drugs in your combination, which is another important aspect of maintaining good levels of adherence. Here are some points to consider about maintaining good levels of adherence:
- Try to take your treatment at roughly the same time each day and observe any food requirement needed to aid absorption.
- Think about every-day tasks you do at a regular time and add taking treatment to a particular task. Maybe think about taking your treatment when you wake up, at a particular meal time, when you get home from work, or before going to bed. Taking your treatment at a time that fits into your daily routine can be beneficial to aid good levels of adherence.
- Regardless of the number of separate pills you take a day it’s worth thinking about getting a 7-day pill organiser. This is a sure yet simple way of identifying if you’ve taken your treatment each day
- Setting an alarm(s)as a reminder can be very helpful, particularly in the first few months after starting treatment.
- If you forget to take your treatment just take it as soon as you remember if it’s within 12 hours of your usual time.
- If you completely forget to take your treatment one day, this isn’t anything to be really worried about. Take it the next day as you usually would.
- We are all human and therefore fallible, there will be times when we forget to take our treatment. As long as this is a relatively rare occurrence your treatment will remain effective and your viral load will remain undetectable.
- If you are having difficulties taking your treatment as prescribed talk to your clinic team as they will support, you to improve your adherence. This can sometimes include treatment simplification by reducing down the number of pills you take, or understand the barriers you may have to achieving good levels of daily adherence.
Modern HIV drugs are generally well tolerated by the majority of people, and any noticeable side effects are short lived. Side effects aren’t compulsory, but there can be occasions where troublesome side effects continue. It’s important to talk to your Dr about any side effects you experience, as it is always possible to make some changes to your combination to help resolve any problems you experience. Here are some points to consider to help manage short term side effects:
- It can take a few weeks for the body to get used to the new drugs, and the first few days can be a little difficult for some people.
- Common side effects that are usually short lived may include nausea, stomach cramps, change in bowel habit, itching, development of rash, headache, dizziness, insomnia and vivid dreams.
- Nausea and changes in bowel habit can be prevented by taking anti-sickness and anti-diarrhoea medication. Antihistamines can help relieve itching and mild rash and headache treated by using over the counter pain relief. It is important to discuss any side effect with your clinic team and to obtain their advice prior to taking any other medications to help reduce side effects.
- Varying the amount of food you have when taking your medication can help reduce nausea and other stomach issues. The exceptions here are combinations that contain rilpivirine (Eviplera, Odefsey and Juluca) which should be taken with a meal (400 calories) and efavirenz, which should be taken on an empty stomach to lessen potential side effects.
- The development of a rash can be a sign of sensitivity to a particular drug. It is important to let your clinic team know about rash that is widespread, very itchy or becomes painful or you experience fever or feel unwell. If this happens when your clinic is closed, it is advisable to attend your local A&E unit to get things checked out. If in doubt always check it out!
- Changing the time you take your treatment can help with insomnia, sleep disturbance and vivid dreams. It can be helpful to see if taking your treatment in the morning rather than evening or before bed helps with this. The only exception to this is a combination that contain efavirenz which is always recommended to be taken before bed, ideally on an empty stomach.
Home delivery schemes
After the first few months from starting treatment your clinic may ask you to consider using a home delivery service for the supply of your treatment. Home delivery is used for a variety of long term conditions and saves the NHS paying VAT on the drug costs. Home delivery is optional, and no one should feel pressured to use the service. Home delivery can be a convenient way of obtaining your treatment, particularly when your appointments are every 6 months. Below is a general summary of how home delivery works:
- Once you’ve seen your Dr or another member of the clinic team who prescribes your medication they will create a prescription which usually goes to the in-house pharmacy for authorisation and then forwarded to the home delivery company. This process may vary depending on local polices in place.
- If you are running short of medication tell your Dr who can arrange a month supply to be given to you from the in-house pharmacy on the day, with the balance being delivered by the home delivery service.
- Once the home delivery company have received your prescription, they will usually contact you to arrange your delivery to your home address, or an alternative address if this is more convenient, maybe a work address as an example.
- Some home delivery companies will deliver to your local community pharmacy (Boots, Lloyds etc.) for you to collect when convenient. The packaging doesn’t identify the medication, so your privacy is assured.
- For deliveries to your home or other nominated address, home delivery companies may use the postal system, or a courier service for your delivery. As above, the packaging doesn’t identify what’s inside, although when handled it’s often possible to identify there is some form of tablets inside, something to be aware of.
- You can opt in or out of a home delivery scheme at any time, which gives you some flexibility or to try the system and see if it’s something that’s convenient for you.
There can be interactions between HIV medications and other prescription drugs, over the counter and some herbal remedies. It’s important to check with a pharmacist or clinic team if there are any particular interactions you should be aware of. Some interactions reduce the effectiveness of HIV drugs, others can increase the levels of other prescribed drugs and the active ingredient(s) contained in over the counter remedies, particularly where your HIV treatment contains a boosting agent. The boosting effect can lead to increased side effects, some of which can be quite serious. The use of steroid medication can be a particular concern as is the use of medication or remedies that help reduce stomach acid. There can also be interactions with some supplements that contain minerals. You can check for drug interactions online by visiting HIV Drug Interaction Checker which is a resource used by HIV clinics and pharmacists and provides up to date information. There is also a smartphone app available on Google play and Apple app store.
An important point here is to contact your Dr or Pharmacist if you have been prescribed additional medications or start taking any over the counter or herbal remedies. It’s always better that where there is doubt, check it out!
Detailed below are some of the more important interactions to be aware of:
- The boosting agent cobicistat which is present in Rezolsta, Evotaz, Stribild, Genvoya or a combination that contains darunavir / ritonavir or atazanavir / ritonavir can raise the levels of other prescription drugs. Of particular concern are the use of steroid medications, either given by injection, used in asthma inhalers or steroid containing eye drops. Topical creams that contain a steroid are generally OK, but it’s always good to check. Some statins may require a dose adjustment when used with combinations that include a boosting agent. It is very helpful to let your GP know the details of your HIV treatment, so he or she can check before they prescribe you a particular drug.
- Supplements that contain minerals such as calcium, magnesium, zinc and iron can reduce the effectiveness of drugs from the integrase inhibitor group (raltegravir, dolutegravir, Triumeq, Stribild, Genvoya). The general recommendation here is there should be a period of separation of at least 6 hours between taking your medication and taking these supplements. From a practical point of view if you take your HIV medication in the morning, take any supplements at night, or vice versa.
- Combinations that contain atazanavir, Evotaz, rilpivirine, Eviplera or Odefsey require an acid environment in the stomach to be well absorbed. Prescription drugs that reduce stomach acid such as omeprazole, lansoprazole, and zantac can reduce the effectiveness of your HIV treatment, so it’s important to check for any possible interactions. Over the counter items that reduce stomach acid (rennie, gavison, tums, Alka Zelster) should be used with caution if at all.
- There are some herbal remedies, notably St John’s Wort, which reduce the effectiveness of several drugs from the NNRTI and Protease Inhibitor groups. There are some other herbal remedies that can have a similar effect, so it’s very important to check with a pharmacist or a member of your clinic team prior to taking any herbal remedies.
- Whilst not an interaction, a sustained period of sickness and diarrhoea where food cannot be tolerated can result in the poor absorption of the drugs in your combination. In situations like this it is advisable to contact your clinic team for further advice. In a similar circumstance if you have an upset stomach and vomit within an hour of taking your treatment it is recommended to try and take it again once things have settled down.
Travel and time zone changes
Many people who take a variety of prescription drugs will be used to travelling and often don’t think twice about carrying medication either in hand luggage or luggage placed in the hold. HIV medications are no different, but it’s natural for some people will have concerns relating to privacy or where some countries have entry restrictions for people living with HIV. Travelling to countries in a different time zones can be a source of anxiety and taking a practical approach to time adherence helps with this and can prevent missed or double doses. Here are some points to consider:
- If you have concerns about travel restrictions some countries may have it’s worth checking HIV travel global database which explains any restrictions for a particular country.
- When traveling outside the UK, it’s good practice to keep your HIV medications in their original containers and to obtain a generic letter, either from your GP or clinic. The letter only needs to explain your medication is for personal use and needs to be taken every day. There is no requirement for any information about the condition your medication is prescribed for.
- Concealing medications in vitamin bottles or other such containers isn’t advisable as this may raise suspicion by customs officials in some countries and could result in things becoming more complex and difficult.
- It is advisable to carry your medication in your hand luggage rather than in the hold luggage as should this go missing there may be a period where you can’t take your medication. It’s useful to take a small back-up supply just in case your return home is delayed for some reason.
- Should your medication go missing it is sometimes possible to obtain a replacement in the country where you are traveling to, particularly within Europe. It’s always worth checking, although there is likely to be a charge, which may not be refundable. If it’s not possible to get replacement medication try to contact your clinic and ask for further advice.
- When travelling in and out of different time zones it can be impractical to continue to take your medications at the time you would normally do when at home. To avoid confusion and more importantly missed doses it is advisable to take your medication at the same local time rather than make an adjustment. The only exception to this where you would miss a dose within a 24-hour period. Medications that are taken twice a may also need some adjustment when travelling, but upon arrival at your destination it is advisable to resume taking your medication at your usual time. If in doubt or you have any concerns its always best to check with your clinic team prior to your travel date.
- Linked to the point above is the change in time where clocks go forward or back here in the UK. There is no need to make an adjustment in the time you take your medication, just keep it to the same time.
Other things to think about are arranging travel insurance and checking the vaccinations you may require for your trip. People living with HIV can obtain travel insurance from non-specialist insurance companies, usually without having to pay a premium. Some insurers will ask information about your treatment, your latest CD4 count result, and if you’re stable and taking treatment. Many people living with HIV search for quotes online, although you may be required to speak to the company concerned where you declare a pre-existing health condition.
Travel vaccinations are generally not problematic as most don’t contain live components, but it’s always worth checking with your clinic team several weeks before you are due to travel and then arranging an appointment with your GP to have the necessary vaccinations done.
Treatment Prescribing Guidelines
In recent years treatment prescribing guidelines have been drawn up by the NHS to reflect safe and effective prescribing and to help manage cost pressures. The NHS in the UK is devolved to the administrations in England, Scotland, Wales and Northern Ireland. This means there are slightly different arrangements in place, but the overall aim remains the same, which is to ensure highly effective, well tolerated treatment is available for everyone living with HIV.
When arriving at a decision about the combination of drugs that will be most effective your Dr will look at the clinical information, your blood results, other health and general information you have provided, and your preference based on practical day to day, lifestyle and work situation. Arriving at a suitable treatment combination that will be the best fit for you is important and should be a decision that both you and your Dr fully discuss, with the final decision being made by the individual concerned.
The following information provides a general overview of the NHS treatment prescribing guidelines which Dr’s and clinic teams take into account when prescribing treatment to people starting treatment for the first time. There are some variations depending on where your clinic is located within the UK.
Clinical information your Dr will consider:
- Results of resistance tests which identify drugs that will be fully active to stop HIV multiplying and therefore rapidly reduce viral load to undetectable levels.
- Your viral load prior to starting treatment as some drugs are only fully effective where viral load is below 100,000 copies.
- The result of a genetic test that identifies a particular reaction to the drug abacavir. A positive result means abacavir isn’t a suitable drug to use.
- Any pre-existing medical conditions, which can include reduced kidney function, low bone density, high risk of cardiovascular disease, depression or other mental health condition.
- The results of other investigations completed as part of your first appointment after diagnosis, or other considerations like wishing to start a family and pregnancy to name a few.
Practical things to talk to your Dr about:
- The importance of having a single pill combination and to explain how this may help with taking your treatment every day.
- How comfortable you feel about taking 2 or more separate pills once a day, and if this would make it difficult to take your treatment every day.
- Any food requirements different drugs have to ensure they are fully effective. If you don’t have regular meal times this can be an important consideration.
- Your work environment, such as shift work, night working, regular travel with work or anything you think may be important for your Dr to consider.
- Any worries you have about privacy due to living arrangements and the impact this may have on your ability to take your treatment every day.
- Other prescribed medications and over the counter remedies you take regularly. Your Dr will need to check for any interactions with your HIV drugs to make sure they remain fully effective and do not cause problems with the other prescription medications you take.
More drugs used for the treatment of HIV are becoming available in generic, non-branded form, which are equally effective, less costly and provide good value for money. Clinics often have local policies in place regarding the use of generic drugs and prescribing guidelines. These policies are informed by Regional and National NHS prescribing guidelines.
Treatment options (starting treatment)
It is well established that where people are fully involved in treatment decisions they are more likely to take medication as prescribed, feel empowered to discuss side effects with their Dr’s, remain linked into care and better self-manage their treatment and care. The overall impact of this is they remain fit and well, which is the prime objective of taking daily treatment.
The information below gives an overview of the likely treatment options your Dr will consider most appropriate for you:
Efavirenz plus a single pill containing lamivudine / abacavir (2 pills taken once a day, taken on empty stomach)
Efavirenz plus the single pill Truvada containing emtricitabine / tenofovirDF (2 pills taken once a day, taken on empty stomach).
If there is a clinical or practical reason why efavirenz isn't suitable for an individual, the following alternative combination is usually considered.
Raltegravir (600mg) plus a single pill containing lamivudine / abacavir (3 pills taken once a day, no food requirement)
Raltegravir (600mg) plus the single pill Truvada containing emtricitabine / tenofovirDF (3 pills taken once a day, no food requirement).
If neither of the above are clinically suitable (drug resistance, pre-existing medical conditions, drug / drug interactions, adherence or side effect concerns) there are several other options that can be considered. Your Dr may refer your case to a multi-disciplinary team (MDT) or regional virtual treatment clinic, which are made up of other Dr’s, and often include specialist HIV nurse practitioners, pharmacists, psychiatric nurses etc. This ensures the most suitable and cost-effective treatment regimen is prescribed for you.
Any one of the combinations listed below can be considered, and should reflect both clinical requirements, BUT also patient choice and agreement. At the moment, it's difficult to identify which of these alternative options would be considered the most cost effective, but they are in the order which may reflect cost, the least expensive at the top.
Triumeq containing dolutegravir / lamivudine / abacavir (single pill, no food requirement).
Rilpivirine plus a single pill containing lamivudine / abacavir (2 pills taken once a day, taken with a meal).
Eviplera containing rilpivirine / emtricitabine / tenofovirDF (single pill, taken with a meal).
Stribild which contains elvitegravir / cobicistat / emtricitabine / tenofovirDF (single pill, taken with some food).
Evotaz which contains (atazanavir / cobicistat) plus a single pill containing lamivudine / abacavir (2 pills taken once a day, taken with some food).
Evotaz which contains (atazanavir / cobicistat) plus Truvada which contains emtricitabine / tenofovirDF (2 pills taken once a day, taken with some food).
Rezolsta which contains darunavir / cobicistat plus a single pill containing lamivudine / abacavir (2 pills taken once a day, taken with some food).
Rezolsta which contains darunavir / cobicistat plus Truvada which contains emtricitabine / tenofovirDF (2 pills taken once a day, taken with some food).
Dolutegravir plus Truvada which contains emtricitabine / tenofovirDF (2 pills taken once a day, taken with some food).
In some circumstances where neither abacavir or tenofovirDF are suitable for an individual the following options can be considered as they contain the new version of tenofovir (TAF) which is thought to be kinder to kidney function and bone health.
Descovy which contains emtricitabine / tenofovirAF (single pill, no food requirement).
Genvoya which contains elvitegravir / cobicistat / emtricitabine / tenofovirAF (single pill, taken with some food).
Odefsey which contains rilpivirine / emtricitabine / tenofovirAF (single pill, taken with a meal).
Biktarvy which contains bictegravir / emtricitabine / tenofovirAF (single pill, no food requirement) ***
Symtuza which contains darunavir / cobicistat / emtricitabine / tenofovirAF (single pill, taken with some food).
Note *** Awaiting EU and or NHS approval for use in the UK.
Sometimes it may be necessary to consider a change in one or more components of your treatment combination. There are now many studies that have specifically looked at comparing different drugs to one another in the context of efficacy, how well they are tolerated and if there are any clinical advantages in making a particular switch. Detailed below are some of the reasons a change in treatment may be considered:
- Ongoing side effects are probably one of the main reasons people switch treatment. There are always options to consider which can help reduce a particular side effect. Ideally, it’s better to switch out one drug at a time (where possible), rather than to switch to a completely new combination, which may not be helpful in identifying which drug component might be causing a particular side effect.
- Changes in clinical markers over time, such as raised liver enzymes, changes in kidney function, cholesterol levels etc. are examples where your Dr may wish to review your medication and suggest a change in one or more components within your combination. This is usually nothing to be concerned about, but important that you understand why the change has been suggested.
- An increase in viral load (above 50 copies) may also necessitate a change in one of more of the components in your combination. Sustained, detectable viral load may be a sign that your combination may not be working effectively. This requires further investigation, a review of previous resistance test results, and where possible, a new resistance test completed to provide the detailed information to identify which drug component may not be fully effective to keep the viral load to undetectable levels. Whilst this can be somewhat unsettling, it’s important that the drugs in your combination are fully effective as this is the overall goal of treatment for HIV.
- Treatment simplification to reduce the number of individual pills taken (pill burden) is another valid reason where a change in treatment may be desirable, or to reduce the number of drugs that make up your combination, this can also include a reduction in the number of drugs your combination contains.
- With the use of more generic drugs within HIV care your Dr may ask you to consider moving from a single pill option to 2 or more separate component drugs that make up that particular combination. We have seen this with a move away from Atripla (single pill) to efavirenz with Truvada (2 pill combination). The opposite can be true where some individuals have been switched from darunavir/ritonavir (2 pills) to Rezolsta (single pill). Your Dr should discuss any treatment switches with you and obtain your agreement prior to any changes being made.
- Occasionally changes to other prescription drugs or the development of another health condition may require a review and changes made to the treatment for HIV. Sometimes this can be for a fixed period of time (during pregnancy, treatment of other conditions) or a more permanent change in treatment. As with any changes in treatment the reason for the change should be clearly explained and your agreement sought prior to any change being made.
Any proposed changes in treatment are usually discussed at a treatment multi-disciplinary team meeting or virtual treatment clinic, particularly where drug resistance or treatment failure is suspected. This is good practice and ensures the most suitable and effective treatment is prescribed.