A study in this week’s issue of THE LANCET suggests that the ability of the immune response to recover after antiretroviral treatment for HIV-1 infection may be dependent on the composition of the MDR1gene, which encodes the P-glycoprotein.
HIV-1-infected patients vary considerably by their response to antiretroviral treatment, drug concentrations in plasma, toxic events, and rate of immune recovery. This variability could have a genetic basis. Amalio Telenti and colleagues from University Hospital, Lausanne, Switzerland, did a population study to analyse the association between response to antiretroviral treatment and variants of several genes.
123 patients with HIV-1 infection took part in the study. The investigators did polymerase chain reaction (PCR) analyses of the gene for the multidrug-resistance transporter (MDR1), which codes for P-glycoprotein. They also assessed genes coding for isoenzymes of cytochrome P450 CYP3A4, CYP3A5, CYP2D6, and CYP2C19, and of the gene for the chemokine receptor CCR5. Concentrations in plasma of the antiretroviral agents efavirenz and nelfinavir was assessed, and levels of P-glycoprotein expression, CD4-cell count, and HIV-1 viraemia was measured.
Drug concentrations in patients with the MDR1, 3435TT, CT and CC genotypes were at the 30th, 50th, and 75th percentiles, respectively. Patients with the MDR1, 3435TT genotype had a greater rise in CD4-cell count 6 months after starting treatment than patients with the CT and CC genotype.
Amalio Telenti comments: “The polymorphism MDR1 3435C/T predicts immune recovery after initiation of antiretroviral treatment. This finding suggests that P-glycoprotein has an important role in admittance of antiretroviral drugs to restricted compartments in vivo.”
Contact: Dr Amalio Telenti, Division of Infectious Diseases, University Hospital, CHUV - 1011 Lausanne, Switzerland; T) +41 21 314 0550; F) +41 21 314 1008; E) amalio.telenti@chuv.hospvd.ch
Journal
The Lancet