Currently available antiretroviral drugs belong to two major classes:
1. Reverse Transcriptase Inhibitors (RTIs)
2. Protease Inhibitors (PIs).
Reverse Transcriptase Inhibitors are further divided into 2 groups:
1.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
1.2 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).
In most industrialised countries a range of antiretroviral agents have been approved, licensed and registered for the treatment of HIV At present, they include:
zidovudine (AZT, ZDV)
All these drugs act by blocking the action of enzymes that are important for replication and functioning of HIV Once HIV invades a macrophage or T-lymphocyte, the enzyme HIV reverse transcriptase initiates copying of the viral genetic code (RNA) into the genetic code of the infected host cells (DNA). After this, HIV genetic material is integrated into the host’s DNA. This is followed by multiplication, creating several billion new copies of HIV per day. The enzyme protease contributes to viral reproduction by enabling the assembly and release of viable particles of HIV from infected cells.
For optimal efficacy antiretroviral drugs, usually from different classes, must be used in combination. A similar approach to therapy is already established practice in the treatment of other important long-term diseases such as cancers, tuberculosis and leprosy. Several combination regimens with demonstrated effectiveness in achieving durable suppression of HIV replication are available.
All available antiretroviral drugs have class-specific adverse effects, which are summarised below. For more details on drug specific adverse effects, see Annex II.
Nucleoside Reverse Transcriptase Inhibitors
(NRTIs) may cause fatty change in the liver, which is reversible upon stopping the medications, or lactic acidosis, a metabolic complication that is potentially fatal if unrecognised. These two adverse effects are due to toxicity of the NRTIs on cellular mitochondria. Changes in body fat distribution as well as derangements in the metabolism of fats, which are described below, have also been associated with the prolonged use of NRTI containing regimens.
(PIs) have been associated with body fat redistribution which manifests physically as thinning of the arms, legs and face and/or deposition of fat in the abdominal and shoulder regions. A further effect of this class of drugs on the metabolism of fat may result in raised levels of serum cholesterol and serum triglycerides, in insulin resistance and rarely in increased blood sugar levels. The overall cumulative incidence of these metabolic disturbances may be 30% to 60% after 1 to 2 years of treatment, increasing with duration of therapy. All drugs in this class may cause bleeding episodes in patients with hemophilia.
Non-Nucleoside Reverse Transcriptase Inhibitors
All NNRTIs may cause a skin rash. These rashes are generally mild and self-limited, though severe forms similar to a Stevens-Johnson syndrome have been reported. NNRTIs may also cause elevation of serum aminotransferases and rare cases of fatal hepatitis have been reported.