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The Role of Antiretrovirals in Treatment
Introduction
Antiretroviral drugs (ARVs) are currently the primary method for treating HIV. These drugs inhibit either of the two enzymes that are essential for HIV replication, namely, reverse transcriptase and protease. Newer drugs target other areas of the virus' lifecycle, but are not yet readily available in our region.
Although antiretroviral treatment is not a cure for HIV/AIDS, it can significantly prolong and improve the lives of HIV-infected people. ARVs slow down the production of HIV and give the body a chance to build up its CD4 cell count which, in turn, helps the body fight against opportunistic infections.
Types of Antiretrovirals
Antiretroviral treatment is usually prescribed as a combination of two or three different types of drugs to combat different processes during HIV replication. The three main types of drugs available are listed below:
Prevents healthy T-cells from becoming infected with HIV by interfering with the reverse transcriptase enzyme which the HIV uses to convert viral RNA to viral DNA.
There is still debate over when to start antiretroviral treatment (ART). Because ART has known side effects, including short and long-term toxic effects on the body, medical specialists disagree over when to start the treatment.
ART guidelines around the world generally recommend treatment begins when the patient has a CD4 count between 350 cells/mm3 and 200 cells/mm3 (depending on the individual) or if he/she is displaying an AIDS-defining illness, such as Kaposi's Sarcoma or wasting syndrome.
The SA National Antiretroviral Treatment Guidelines recommend that a patient begins ART when the patient's CD4 count is below 200, or s/he has displayed an AIDS-defining illness. These are undergoing constant revision.
Current treatment guidelines in Europe and the United States for example, recommend that ART begins before the CD4 cell count falls below 200 cells/mm3 - the exact timing depending on the individual patient's condition. Because of known toxicities and resistance, and unknown long-term effects, most doctors see no benefit in beginning treatment in patients until their CD4 counts drop to a level between 350 cells/mm3 and 200 cells/mm3.
According to the South African guidelines, patients must also display a willingness and readiness to take antiretroviral treatment adherently. If patients don't take their treatment properly, their treatment will probably fail and the virus in their body will become resistant to the drugs. (See treatment adherence below.)
Drug Resistance
Because HIV reproduces itself so rapidly, slight mistakes or mutations develop in the virus. Some of the mutations occur in parts of the virus targeted by the antiretroviral drugs. If a patient is only taking one drug, these mutations are likely to survive the treatment and spawn similar drug-resistant strains. If the patient is taking two or three different drugs, the mutation is less likely to survive as the other drugs will target different areas where there is no mutation and stop it from producing strains.
This is why combinations of antiretrovirals are prescribed in most AIDS treatment plans.
When a patient begins antiretroviral treatment, their viral load normally falls to undetectable levels. If drug-resistance begins, the viral load will rise as the new strain populates the body. When this happens, patients are usually prescribed a different regimen of drugs that will target other parts of the virus. When a second or third-line regimen becomes ineffective, a patient can run out of antiretroviral treatment options.
Treatment Adherence
Similarly, treatment adherence is an essential part of a treatment programme. If a patient does not take their treatment correctly, there is a major risk of drug resistance as mutations will be allowed to develop between their intermittent treatment.
If a patient takes less than 95% of his/her doses, they are at risk at developing virological resistance to the treatment
If a patient takes less than 80% of his/her doses, their treatment is unlikely to be successful
Drug-resistant strains of HIV can be transmitted by people. A person infected by a drug resistant strain will be as limited for treatment options as the person who infected them.
Side Effects
People taking antiretroviral drugs are likely to experience some side effects during their treatment. But most scientists and doctors agree that the benefits of antiretroviral treatment outweigh the side effects of the drugs. It is important that patients are made aware of known side effects so they maintain their treatment adherence whenever possible.
Possible major side effects to antiretroviral drugs include:
Lipodystrophy and Wasting - changes in the amount and distribution of body fat and body muscle
Facial Lipoatrophy - loss of body fat around the face (e.g. sunken cheeks)
Hyperlipidemia - increases in blood lipids, notably cholesterol
Fatigue and Anemia - lack of energy which can be caused by red blood cell count dropping
Peripheral Neuropathy - nerve damage causes tingling or burning in hands or feet
Nausea and Diarrhoea - upset stomach and liquid stool
Hepatotoxicity - liver damage caused by medication
A patient may also experience short-term minor side effects. (Source: AidsMeds)
Access to Antiretroviral Drugs
Global Situation
The World Health Organisation estimates that of the 6.5-million people who required antiretroviral therapy in the developing and transitional world in June 2005, only 970,000 (15%) received it.
WHO: ARV therapy coverage in low and middle income countries, June 2005
South Africa's controversial AIDS treatment history over the last decade has resulted in considerable media focus and attention. After years of withholding general antiretroviral treatment in the public health sector, arguing that the drugs were toxic, unaffordable and inappropriate, the SA Cabinet announced its approval of the SA National Department of Health's Operational Plan for Comprehensive HIV and AIDS Care, Management and Treatment for South Africa (1.9MB) in November 2003. The five-year plan provides for ARVs to be made available in the public health sector for the first time on a large scale. However, as detailed in the WHO report highlighted above, the implementation of this plan has been slow.
The Cabinet announcement cited "favourable conditions" including falling drug prices and growing experience in fighting HIV/AIDS as reasons for the implementation of the plan at this stage.
Planned number of patients on antiretroviral treatment vs no. of new AIDS patients per year
Years
ARVs
Total Cases on ARVs (planned)
Projected total new AIDS cases*
2003/2004
53,000
53,000
388,701
2004/2005
138,315
188,665
462,841
2005/2006
215,689
381,177
530,658
2006/2007
299,516
645,74
586,181
2007/2008
411,889
1,001,534
624,720
*Data from Table 16.1. Represents new AIDS cases per year and not a culmative total.
However, the government was not able to meet its own projections as set out in the table above. By March 2005 about 104,600 people (44,600 public sector; 60,000 private sector) were being treated with ARVs in South Africa, out of a WHO-estimated 837, 000 who need the treatment (Dec 2004). This had increased to over 300 000 by the middle of 2007, still far behind anticipated need.
