In 2016 it was estimated that Zimbabwe had 1,3 million people living with HIV infection. During this period there were about 30 000 AIDS related deaths. The use of Antiretroviral drugs has had a major impact on morbidity and mortality. More people are surviving and living with HIV infection and are free from opportunistic infections.
As the National Antiretroviral Programme rolls out more and more people are accessing Antiretroviral therapy. This increase in the number of people on treatment will also be associated with a rise in numbers of individuals whose treatment fails whilst they are on therapy. The subject of this article is to look at this group of individuals whose drugs fail to work.
Antiretroviral treatment failure can be looked at in three broad categories.
- Virologic failure;
- Clinical failure;
- Immunologic failure.
Virologic failure is when the amount of virus in one’s blood fails to decline below a certain defined level after commencing treatment with Antiretroviral drugs. It can also occur after initially suppressing the virus adequately and then there is an increase in the amount of virus in the blood. Most clinicians use a cut off point of 200 copies per mL of blood to define virologic failure. Some centres use a higher cut off point of a virus load greater than 1 000 copies per mL of blood.
The World Health Organisation has recommended that virus load testing be used as the gold standard for monitoring response to Antiretroviral therapy. Clinical failure can be used indirectly to suggest that an Antiretroviral regimen is failing.
When an individual who is HIV positive commences Antiretroviral therapy we expect them to feel better, gain weight and be free from opportunistic infections. If there is a worsening of the general health of the patient this may suggest clinical treatment failure.
Immunologic failure can mean several things to different health care givers. A drop in the CD4 count after an initial improvement whilst on treatment is immunologic failure. A failure to achieve a robust increase in one’s CD4 count can also be described as immunologic failure even if it occurs in an individual who has virologic suppression.
Causes of treatment failure
- Poor adherence: This refers to erratic intake of medications. Poor adherence is probably the commonest cause of treatment failure. Causes of poor adherence to Antiretroviral therapy include:
(i) Failure to understand instructions on how to take the medicines.
(ii) Stigma issues. I may not be comfortable to take my pills when there are people watching me. The same applies to children. Parents may not give them drugs when there are visitors around or when there is no privacy.
(iii) Co-morbid states such as psychiatric illnesses can also lead to erratic intake of antiretroviral drugs.
- Transmitted drug resistance: This occurs when the virus that has infected an individual is inherently resistant to the commonly used Antiretroviral drugs. It may also occur when an individual gets re-infected by a resistance strain when they are already on treatment.
- High virus load at commencement of Antiretroviral therapy: The higher the virus load at starting therapy the more likely that the virus may escape through and develop resistance. There are certain combinations of Antiretroviral drugs that cannot be used when the virus load is above 100 000 copies per mL of blood.
4 Unintentional drug interruption: There are circumstances when for medical reasons a patient may be asked not to take anything orally. For example after certain types of surgery. Healthcare givers always try to minimize such events.
- Drug related reasons for treatment failure:
(i) Certain combinations of Antiretroviral drugs have been known to have side effects that may affect adherence. For example in Zimbabwe we once used combinations that were more likely to cause neuropathy (painful/burning sensation of the feet).
There are certain combinations that may lead to excessive sleepiness, vivid dreams and dizzy spells. Such potential side effects should be carefully discussed with the patient and choices where possible are made to use regimens that have minimum side effects.
Simple practical measures to reduce side effects need to be explored. For instance you cannot give a long distance driver who mainly works at night treatment that has to be taken at night and also makes them sleepy.
- Suboptimal regimens: There is a substantial number of combinations now available for use as Antiretroviral Therapy. Some of them have been known to be weaker than others.
Therefore one needs to always choose a combination that is robust and has a good track record. Using national guidelines is one way of ensuring that you are using an accepted and robust regimen.
- Prior exposure to poor regimens: During the early part of the HIV epidemic there were some regimens that were used which were suboptimal and failed to achieve sustained virologic suppression.
Such regimens may continue to have an impact on future options you use. In other words you may develop drug resistance to a drug that you have not used before but could have been exposed to another in the same class in the past. This is called cross-resistance.
- Food requirements: It is important to look carefully at the potential for food interactions with an antiretroviral regimen. Some medicines are poorly absorbed when taken together with certain foods and this can lead to failure.
- Prescription errors: Under dosing or the wrong duration of taking drugs may occur accidentally.
10 Systems failure: I may have the money to buy the drugs. I may be registered with a clinic for accessing my drugs. The system can fail me if I get there and there is a stock out for various reasons. Logistics is therefore an integral part of managing HIV.
The impact of treatment failure
Failure of Antiretroviral drugs will fuel the epidemic. There will be an increase in morbidity and mortality secondary to HIV infection. It limits the number of drug options available for combating the epidemic.
Treatment failure will lead to an increase in the overall cost of health care at individual and national level. The current gains obtained from the roll out of Antiretroviral therapy will be lost if we have increasing treatment failure.