By Lizzie van Dorp
The previous blog ‘Treatment of HIV/AIDS’ already outlined the types of antiretroviral medications available and briefly mentioned the possible risks of ART. The WHO recommends commencement of antiretroviral therapy for all seropositive individuals regardless of CD4 count and viral load. Chances of progression to AIDS and forward transmission diminish with antiretroviral therapy, while quality of life and life expectancy increases.1,2 Antiretroviral treatment can expand the life expectancy of people progressed to AIDS (with ART 61% at least an other 10 years; without 48% about an other 2 years).2,3 The antiretroviral medication is effective but can have adverse effects. These adverse effects are usually manageable and disappear over time but some can be serious. The side effects of the drugs as well as the tests that needs to be done to properly treat a person with HIV will be discussed here.
Possible tests
The previous blog on HIV diagnosis already described the multiple ways to assess whether someone is infected with HIV. To monitor the progression or stabilization of an HIV-infection and screen for co-morbidities multiple tests are possible. Screening for co-morbidities, diseases and conditions frequently seen in combination with an HIV-infection that can become more severe due to the lowered immune system caused by the HIV-infection, is also necessary. Furthermore, when people receive antiretroviral therapy assessing the function of kidneys and liver function and the amount of red and white blood cells in an FBC (full blood count) can help determine whether and when to switch therapies. Bone density should also be assessed, as ART can cause osteoporosis, frail bones.3,4When treating people with HIV the WHO reinforces that all HIV testing services should adhere to the 5 Cs. Consent and confidentiality are important, as is pre- and post-test counselling tailored to the person. Besides giving the correct results to the person in question, the correct tests should be performed. Testing for HIV should be supported connections to follow-up steps.4,5
- CD4 count - Blood test. The CD4 count determines the staging of an HIV-infection
- Viral load- Blood test. The amount of HIV-RNA, or HIV genetic copies in the person’s blood.
- Full blood count- Blood test. Counting the amount of red and white blood cells and platelets. Important in checking for anaemia, a side effect of some NRTI’s
- Renal Function- Blood test. Important for determining the dose of medication. Kidneys are a major organ filtering out waste products. If kidneys function less, waste products or medication build up inside the body and can reach toxic levels. Monitoring is important because some of the ARV’s can cause renal function to be impaired.
- Liver Function- Blood test. When the values of the liver function are not within normal limits before starting treatment, causes should be determined and treated where possible. Some NNRTI’s and PI’s can cause a deterioration in live function.
- Pregnancy test– to prevent mother-to-child, or vertical transmission by adequately starting treatment for the mother.
- Testing for other diseases more frequently seen in people with HIV: Tuberculosis, Hepatitis B, Cervical abnormalities, STIs
- Bone density – Scan. Both HIV-infection as well as ART can cause bones to become less dense.
- Testing for HLA-B*5710 gene – Blood test. Abacavir can cause serious adverse effects if HLA-B*5701 is present. 1,3
Complications
Antiretroviral therapy has medication specific physical complications, as well as financial and social consequences and limited availability of drugs worldwide. Resistance to antiretroviral drugs is a problem to which a later blog will refer.
Side Effects
The World Health Organization-preferred first line treatment of choice is a once-daily fixed-dose combination. Within the first line of treatment, the first possible medications to try, a combination of two NRTIs (abacavir, lamivudine, tenofovir or emtricitabine) and an NNRTI (efavirenz or nevirapine), PI (atazanavir) or InSTI (dolutegravir). However, the wide range of medicine available in high-resource settings, might not be available in low-resource settings. Some antiretrovirals, such as the NRTI Stavudine, are being phased out of use, due to toxicity. 1,3,6
NRTIs are known to induce mitochondrial toxicity, which means NRTIs have the potential to damage the cells energy producer and thus cause the cell to die. Most often this happens in cells of the pancreas, nerves, fat cells and hepatocytes (liver cells). Damage to the nerves causes peripheral polyneuropathy, damage to the small nerves in for example hands or feet which can cause anything from a slight tingling sensation to sharp pains. NRTIs can also cause lactic acidosis, the build-up of lactic acid in the blood causing nausea, vomiting and muscle weakness. More specifically, Tenofovir can cause the kidneys to fail, lamivudine can cause anaemia, as well as Zidovudine. Abacavir should be avoided in people with the HLA-B*5701 gene, as hypersensitivity can occur, worsening with continued intake of Abacavir. The hypersensitivity can range from a rash and gastrointestinal problems to constriction of the airway.7,8,9
NNRTIs are not known to have a class-related adverse effect, besides skin effects ranging from a rash to Steven-Johnson Syndrome, a severe blistering skin disease. Neuropsychological symptoms can also occur. Efavirenz and Nevirapine can have a low barrier for HIV to turn resistant, since only one mutation renders the first-line of them useless. Furthermore the potential hepatic side effects can lead to severe hepatitis or even hepatotoxicity (liver infection and liver toxicity). Therefore, liver function tests should always be done before starting therapy. The balance of glucose and fats within also has the potential to be disturbed, causing diabetes, hyperlipidaemia and heart disease.10
PIs have a wide range of possible side effects ranging from gastrointestinal problems such as diarrhea, nausea and vomiting to toxicity of kidneys and liver
InSTIs are well tolerated, in general. However, especially in the elderly, insomnia, anxiety, depression and suicidality have been observed.11
Immune restoration disease
Three weeks after starting ART immune restoration disease (IRD) can occur in people who are extremely immunodeficient, in other words in case of a severely progressed AIDS. Opportunistic infections, infections that occur when the immune system is very weak, can cause a vehement reaction by the newly rebooted immune system, resulting in people appearing sicker than before starting ART. Tuberculosis and cryptococcal meningitis are infections notorious for causing IRD. The opportunistic infections should be treated, ART should not be stopped. In severe cases glucocorticoids, a synthetic hormone with anti-inflammatory purpose, may be given.12
Adherence to therapy
Adherence to the lifelong treatment is dependent on the social situation of the person, clinical condition amount of pills to be taken and their side-effects. The effects of relationships with health care providers is also of influence. Regular appointments should be made to check up on ART adherence, as increasing the person's understanding of the situation. Stigma or lack of access to care are important barriers to be crossed. Not adhering can cause drug resistance.10
Inequality
Ninety percent of the people living with HIV live in low-resource settings. The extensive and luckily growing amount of ARVs is not available to all. Not only are some drugs simply not available in some countries, some should be kept refrigerated, something which is not available to all. Inequality is not necessarily a complication of ART, but it is of major importance if the AIDS epidemic is to be stopped by 2030, and should be mentioned here. 3,6,13
1 WHO Consolidated Guidelines on HIV prevention, diagnosis, treatment and care for key populations. 2016 update. http://apps.who.int/iris/bitstream/handle/10665/246200/9789241511124-eng.pdf?sequence=1
2 Poorolajal J. et al. Survival rate of AIDS disease and mortality in HIV-infected patients: a meta-analysis. 2016. Public health 139;3-12
3 Beeching N, Gill G. (2016). Tropical medicine lecture notes (7thedition). West Sussex, UK: John Wiley & Sons.
4 http://www.unaids.org/sites/default/files/media_asset/2017_WHO-UNAIDS_statement_HIV-testing-services_en.pdf
5 http://www.who.int/mediacentre/factsheets/fs360/en/
6 Farmacotherapeutischkompas.nl
7 Boubaker K et al. Hyperlactatemia and antiretroviral therapy: The Swiss HIV Cohort Study. 2001 Clinical Infectious diseases. 33(11);1931-1937
8 Meintjes G et al. Adult antiretroviral therapy guidelines 2017 Southern African Journal of HIV Medicine. 18(1). Published online.
9 Hewitt RG. Abacavir Hypersensitivity Reaction. 2002 Clinical Infectious Diseases. 34(8);1137-1142
10 https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0
11 Fettiplace A et al. Psychiatric symptoms in patients receiving Dolutegravir. 2017. J Acquir Immune Defic Syndro 74(4);423-431
12 Mayer KH, French MA. Immune Reconstitution Inflammatory Syndrome: A Reappraisal. 2009 Clinical Infectious Diseases 48(1);101-107
13 http://www.unaids.org/en/resources/documents/2014/JC2686_WAD2014report