Anti-retroviral Treatment (ART)

4.1 Introduction

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. Although ART 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.

4.2 Types of ARVs

ART 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:

Also see: "Positively Aware" The 13th Annual HIV Drug Guide

4.3 When to Start ART

A summary graphic of the SA National Department of Health's ART procedure contained in the National Antiretroviral Treatment Guidelines.
Credit/Copyright: Department of Health (2004).

There is still debate over when to start 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.

Some countries' guidelines provide for ART before the CD4 count has dropped to this level. 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 ART 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.)

4.4 Recommended Treatment Regimens in South Africa

In South Africa, two standard regimens or treatment options for adults with CD4 counts lower than 200 are recommended in the National Antiretroviral Treatment Guidelines. Patients who fail both regimens are continued on treatment until there is no further clinical benefit. They are then referred to home-based and palliative care.

National Antiretroviral Treatment Guidelines: Treatment Regimens
1. First-line Therapy (Adults)
First-line Therapy (i.e. the first line of treatment) is given to all patients who haven't been exposed to ARVs before. (Those who have had previous ART are referred to specialists.) Women of child-bearing age take nevirapine instead of efavirenz if they cannot reliably prevent conception, due to the risk of birth defects.
1a	Stavudine (d4T) AND lamivudine (3TC) AND efavirenz (EFV)
1b	Stavudine (d4T) AND lamivudine (3TC) AND nevirapine (NVP)
2. Second-line Therapy (Adults)
Patients who do not respond to the treatment (e.g. their viral load remains high) should be changed to Second-line Therapy.
2a	Zidovudine (AZT) AND didanosine (ddI) AND lopinavir/ritonavir (LPV/r)
Source: National Antiretroviral Treatment Guidelines

4.5 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 ARV drugs. If a patient is only taking one drug (monotherapy), 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 ARVs are prescribed in most AIDS treatment plans.

When a patient begins ART, 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 ART options.

4.6 Treatment Adherence

Anton Hame/Perinatal HIV Research Unit (PHRU)

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.

The National Antiretroviral Treatment Guidelines define "ideal adherence" when a patient takes more than 95% of his or her doses. According to the guidelines:

• 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.

4.7 Side Effects

People taking ARV drugs are likely to experience some side effects during their treatment. But most scientists and doctors agree that the benefits of ART 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 ARV 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.

A summary of reported ARV drug side effects developed by Project Inform appears below:

For more information regarding side effects people may experience, see Avert's article "Antiretroviral drug side effects."

4.8 Studies of ARV Drug Effectiveness