HIV Treatment (Overview)
Dipl.-Biol. Birgit Busse
Genetic disposition of a patient is one factor determining efficacy and compatibility of HIV treatment. Polymorphisms in the genes that interact with the active agents play a major role.
The enzyme CYP2B6 is involved in the metabolism of efavirenz. The CYP2B6*6 allele (c.516G>T) is associated with a decreased enzyme activity which may lead to side-effects caused by efavirenz (prescribing information Sustiva®).
HAART and Genetic Variants:
During “Highly Active Antiretroviral Treatment” (HAART), a combination of several drugs are administered at the same time to increase the chance of successful treatment. The enzymes CYP2D6 and CYP3A4 are involved in the degradation of various HIV drugs. P-Glycoprotein (ABCB1 gene) is responsible for the transport of active agents. Variants in the respective genes can alter efficacy of the treatment. A 32 bp deletion in the CCR5 gene results in a non-functional receptor and seems to be associated with a better response to treatment according to the HAART regimen. Polymorphisms in the CCR2 gene (V64I) and the SDF1 gene (SDF1-3'A) play a role in the course of the disease and the prognosis of treatment.
Maraviroc is an entry inhibitor for CCR5-tropic HIV strains, which prevents the virus from entering by blocking the receptor. A functional CCR5 receptor is necessary for a response to treatment. Therefore the 32bp deletion in the CCR5 gene is an indicator for response to treatment.
The HLA-B*57:01 allele is of importance for the treatment with the nucleoside analogue abacavir, since carriers of this subtype frequently exhibit hypersensitivity towards the active agent. HLA typing prior to treatment should be taken into consideration.