By Tessa Lawson Tattersall
Presently, HIV has neither a cure nor a vaccine. However, highly effective treatment regimens can allow for long and healthy lives of people who have been diagnosed as HIV positive in locations where treatment is available and accessible1.
Antiretroviral Therapy
Currently, treatment of HIV is in the form of antiretroviral therapy (ART), which uses a combination of antiretroviral (ARV) drugs that suppress the viral replication of HIV. ART allows the immune system to strengthen and fight infections thus halting the onset of Acquired Immunodeficiency Syndrome (AIDS)2.
There are six categories of ARV drugs: Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase inhibitors (NNRTIs), Protease Inhibitors (PIs), Integrase Inhibitors (INIs) and drugs that interfere with viral entry (fusion Inhibitors and CCR5 antagonists)3. In short, treatment consists of fixed-dose combination or single dosed pills ranging from 1 to 3 pills a day depending on the regimen. Health providers are responsible to conduct detailed discussions on dosage, scheduling, benefits, side effects, and follow-up visits following HIV diagnosis.
How do HIV medicines work?
HIV is an RNA virus that uses viral enzymes to integrate into human DNA within immune cells. HIV can thus use the body’s machinery to replicate and infect further human immune cells, escalating the infection. To indicate the severity of HIV and the effect of treatment, two tests are conducted: the CD4 count and viral load. CD4 count is a representation of how well an immune system functions, a higher CD4 count indicates a better functioning system. HIV attacks T-cells, in which CD4 glycoprotein lies on their surface, by turning them into HIV factories, which in turn destroys the cell, and decreases the CD4 count. Viral load is an indication of the amount of HIV within the blood by measuring the number of copies of HIV RNA in a millilitre of blood. The lower the viral load, the lower amount of HIV is infecting and killing T-cells4.
ARVs inhibit various viral enzymes critical to HIV replication cycle. Specifically, there are six classes of drugs, used in combination, to treat HIV.
Entry Inhibitors interfere with binding, fusion and entry of HIV to the host cell by blocking the co-receptor on the T-cell cell. NRTIs and NNRTIs inhibit reverse transcription, the method of transcribing RNA of HIV to DNA in order for integration of HIV into human DNA, in different and non-competitive ways. INIs inhibit the viral enzyme integrase which is responsible for integration of HIV viral DNA into human DNA of the infected T-cell. Lastly, PIs block the viral protease enzyme, a cutting enzyme which is necessary to produce mature HIV virions budding from the host T-cell5.
In addition to ARVs some combination pills also contain pharmacokinetic enhancers known as boosters.
They inhibit the enzymes that metabolize some ARVs such as PIs. The boosters allows the medicine to be metabolized slower in the liver and stay in the bloodstream for a longer period. When used without a booster PIs needed to be taken twice or three times a day which increases pill burden and risk of toxicity. The boosters have enabled reduction in the dosing of PIs which has also helped to improve treatment adherence and reduce risk of resistance.
What HIV medicines are included in an HIV regimen?
ART is a lifelong commitment. The regimen initially sought, the first-line, generally consisting of two NRTIs (called backbone of the treatment) combined with one drug from NNRTIs or INIs or PIs, is particularly important as immunological improvement and viral suppression is expected. However, baseline resistance and adverse drug reactions may develop in the first three months. An area of caution includes those commencing ART while with severe immunodeficiency and existing conditions as opportunistic infections and immune reconstitution inflammatory syndrome associated with AIDS may inhibit success of ART.
Second- or third-line treatment regimens are sought if adverse effects, virological failure, or no effect due to resistance resulted from the first-line regimen or if the first-line regimen is not available in that location. For example an integrase strand transfer inhibitor (InSTI) may be considered, which blocks HIV from using integrase to insert its viral DNA into the DNA of the T-cell. Thus, for each component of a regimen, specific situations can dictate different recommended and alternative agents3.
When to start HIV treatment?
The World Health Organization recommends that all people with a positive HIV diagnosis seek treatment, regardless of CD4 count, an indication of how well one’s immune system is functioning6. Treatment seeks to prolong the life of people who diagnosed positive for HIV, as well as preserve and enhance the immune system. A functioning immune system will prevent onset of AIDS and related conditions.
What are the risks?
Those on ARV drugs are susceptible to potential side effects of which are screened for directly after HIV diagnosis. Short-term effects, most prevalent when starting treatment, include nausea, headache, fever etc. Long-term effects include loss of bone density (osteoporosis), kidney problems, liver damage, heart disease, and diabetes. As all bodies are different, side effects vary and should be discussed with a health care provider regularly. However, the benefits of ART vastly outweigh the risks7.
Furthermore, taking ARVs intermittently or occasionally will lead to drug resistance. Dangerously, the development of drug resistance would lead to limitations in the number of effective ARVs as resistance to one ARV drug can lead to a cross-resistance to all drugs in that ARV class3. In turn, HIV could no longer be treated successfully, leading to disease progression and transmission of the drug resistant virus to other individuals.
1 BC-CfE. Therapeutic Guidelines for Antiretroviral (ARV) Treatment of Adult HIV Infection British Columbia Centre for Excellence in HIV/AIDS. 2015 [cited 2018 Mar 23]; Available from: http://www.cfenet.ubc.ca/sites/default/files/uploads/Guidelines/bccfe-art-guidelines-Oct_14_2015.pdf
2 WHO | HIV/AIDS. WHO [Internet]. 2017 [cited 2018 Mar 22]; Available from: http://www.who.int/mediacentre/factsheets/fs360/en/
3 Thompson MA, Aberg JA, Cahn P, Montaner JSG, Rizzardini G, Telenti A, et al. Antiretroviral Treatment of Adult HIV Infection. JAMA [Internet]. 2010 Jul 21 [cited 2018 Mar 22];304(3):321. Available from: htp://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2010.1004
4 Treatment Decisions for HIV - HIV/AIDS [Internet]. [cited 2018 Mar 26]. Available from: https://www.hiv.va.gov/patient/treat/decisions-single-page.asp
5 The use of antiretroviral drugs for treating and preventing HIV infection. 2016 [cited 2018 Mar 22]; Available from: http://apps.who.int/iris/bitstream/handle/10665/208825/9789241549684_eng.pdf;jsessionid=9CF55B0D885480B31C02A7BFF17C8567?sequence=1
6 Isobe M, Huebner K, Maddon PJ, Littman DR, Axel R, Croce CM. The gene encoding the T-cell surface protein T4 is located on human chromosome 12. Proc Natl Acad Sci. 1986;83(12).
7 Adverse Effects of ARV | Limitations to Treatment Safety and Efficacy | Adult and Adolescent ARV | AIDSinfo [Internet]. 2017 [cited 2018 Mar 22]. Available from: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/31/adverse-effects-of-arv