Resistance to various antiviral agents is increased by underdosing, monotherapy and irregular dosings. New drugs will be necessary. There are various drugs with antiviral activity that are at present still in an experimental stage. Lodenosine, entecavir, emivirine, capravirine, calanolide A and diaminopurine-dioxalane are just a few of a wide range of drugs. An Indian company produces the combination nevirapine 200 mg + stavudine 30/40 mg + lamivudine 150 mg under the name Triomune®. Fluorocytidine shows activity against both HIV and HBV. A once-daily dose of 200 mg reduced HIV viral load by 1.9 log copies/ml.
Hydroxyurea (Hydrea®) has an antiviral activity and is synergistic with ddI, but potentiates the toxicity of the latter (idem D4T). The mode of action is still not clear, though hydroxyurea probably inhibits the synthesis of deoxynucleotides by blocking the enzyme ribonucleotide reductase. Its routine use is not recommended, since its clinical efficacy has not yet been demonstrated.
The following products are not often used:
Delavirdine (Rescriptor®): not available in Europe. It is associated with maculopapulous rash and itching, fever, conjunctivitis and joint pain.
Loviride is no longer used.
Adefovir dipivoxil (Preveon®). This is a nucleotide-analogue and has been abandoned. This substance contains a phosphoryl group and does not need to be phosphorylated (does not require any intracellulair transformation to form an active molecule). Due to possible side-effects on the mitochondria, it was best taken together with L-carnitine. The latter compound has an important role in the transport of long-chained lipids through the membranes of mitochondria. These latter have a role in energy production (beta-oxidation) and in the production of cardiolipine, a phospholipid (diphosphatidylglycerol).
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