Multidrug resistance proteins

As described above, the multidrug resistance proteins are important in determining the rate of absorption of many drugs, as well as their intracellular levels. A number of polymorphisms in the genes for these proteins have been linked to changes in blood levels of antiretrovirals, with many of these being mirrored in the severity of their side-effects.

For example, the C3435T polymorphism of multidrug resistance-1 (MDR-1) gene has been linked to a decreased risk of liver toxicity in patients taking nevirapine (Viramune) or efavirenz (Sustiva).1 2 This agrees with the observation that levels of these drugs are lower in patients with this polymorphism, at least in some studies.3

Similarly, C3435T is linked to lower blood levels of atazanavir (Reyataz), and less severe elevations in bilirubin in the blood.4 Hyperbilirubinaemia is a major side-effect of atazanavir treatment, which causes a yellowing of the skin and the whites of the eyes. Although visible, hyperbilirubinaemia is not a dangerous side-effect.

The same polymorphism has also been associated with body fat and metabolic changes as a side-effect of HIV treatment. For example, patients with C3435T have lower levels of high-density lipoprotein (HDL) cholesterol with efavirenz treatment.5 HDL cholesterol is beneficial for protection against cardiovascular disease. A further study has linked the polymorphism to a reduced risk of fat accumulation around the organs, and patients with one C and one T version of the polymorphism had elevated total cholesterol levels.6


  1. Haas DW et al. Pharmacogenetics of nevirapine-associated hepatotoxicity: an adult AIDS clinical trial group collaboration. Clin Infect Dis 43: 783-786, 2006
  2. Rotger M et al. Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J Infect Dis 192: 1381-1386, 2005
  3. Fellay J et al. Response to antiretroviral treatment in HIV-1 infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359: 30-36, 2002
  4. Rodrguez Novoa S et al. Plasma levels of atazanavir and the risk of hyperbilirubinemia are predicted by the 3435C-T polymorphism at the multidrug resistance gene 1. Clin Infect Dis 42: 291-295, 2006
  5. Alonso-Villaverde C et al. The efavirenz-induced increase in HDL-cholesterol is influenced by the multidrug resistance gene 1 C3435T polymorphism. AIDS 19: 341-342, 2005
  6. de Luca A et al. The effect of polymorphism of the MDR-1 gene on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected patients starting antiretroviral therapy. 13th Conference on Retroviruses and Opportunistic Infections, Denver, abstract 766, 2006
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.