Apolipoproteins are molecules responsible for transporting cholesterol and other lipids around the body. Variations in the genes encoding these proteins have been linked to hardening of the arteries and to elevated blood triglyceride levels in studies of HIV-negative people. These include variants of the genes for apolipoprotein C3 and apolipoprotein E.

Studies have shown that HIV-positive patients are also at risk of unfavourable changes in blood fat levels if they have these variants. These include polymorphisms in the promoter region for the apolipoprotein C3 gene at three positions (-C482T, -T455C and C3238G) and two alleles of the apolipoprotein E gene (e2 and e3). Patients with these unfavourable polymorphisms are at risk of extreme elevations in blood triglyceride levels when treated with antiretroviral drugs, particularly ritonavir (Norvir). This raises the risk of cardiovascular problems, such as future heart attack and stroke.1 2 Similarly, the C1131T polymorphism in the APOA5 gene is associated with increased triglyceride and cholesterol levels in patients taking protease inhibitors.3 Other studies have identified groups of polymorphisms in these and other genes that are linked to greater elevations in blood lipids than single genetic changes.4

However, this area of research is particularly controversial, with a large number of associations being found in some studies and contested by others. An example of this is one study that found a range of polymorphisms in the apolipoprotein C3 gene were linked to triglyceride levels in Hispanic people, but not in Caucasians or African patients.5

Studies have also found links between certain apolipoprotein polymorphisms and an enhanced elevation of high-density lipoprotein (HDL) cholesterol in patients taking efavirenz (Sustiva). HDL cholesterol is associated with a reduced risk of cardiovascular disease and is often referred to as the ‘good’ cholesterol. One study found that a set of polymorphisms in the apolipoprotein genes was linked to higher levels of HDL cholesterol, which could lead to a reduced risk of heart attacks or strokes.4

These genes have also been linked to the risk of fat loss in preliminary studies. For example, one study has found an association between a polymorphism at position -433 of the apolipoprotein C3 gene and the risk of lipoatrophy. In a study of nearly 300 patients, those who were heterozygous at this position (CT) were over six times more likely to have fat loss than those with two C alleles. In this study, patients were taking a range of anti-HIV drug combinations.6 However, these findings require confirmation in larger studies.


  1. Fauvel J et al. An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride / low HDL levels in treated HIV patients. AIDS 15: 2397-2406, 2001
  2. Tarr PE et al. Modeling the influence of APOC3, APOE, and TNT polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. J Infect Dis 191: 1419-1426, 2005
  3. Guardiola M et al. Protease inhibitor-associated dyslipidemia in HIV-infected patients is strongly influenced by the APOA5-1131T->C gene variation. Clin Chem (online edition), 2006
  4. Arnedo M et al. Modeling the influence of polymorphisms of several genes involved in lipid metabolism on the risk of antiretroviral-associated dyslipidemia. 13th Conference on Retroviruses and Opportunistic Infections, Denver, abstract 764, 2006
  5. Foulkes AS et al. Associations among race / ethnicity, ApoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med 3: e52, 2006
  6. Cossarizza A et al. FAS-670 and APOC3 polymorphisms as predictors of lipoatrophy in patients receiving antiretroviral therapy. 13th Conference on Retroviruses and Opportunistic Infections, Denver, abstract 767, 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.