Statins are a class of drugs used to treat high lipids, especially high LDL cholesterol. They include simvastatin (Zocor), pravastatin (Lipostat), fluvastatin (Lescol / Lescol XL), atorvastatin (Lipitor) and rosuvastatin (Crestor). The statins are more effective than other classes of lipid-lowering drugs at reducing LDL cholesterol, but less effective than the fibrates in reducing triglycerides and increasing HDL cholesterol. In the general population, they reduce the risk of heart disease, stroke, diabetes and death.

Statins are generally regarded as very safe drugs, although their main side-effects are gastrointestinal problems (nausea, vomiting, flatulence and stomach pain) and inflammation of the muscles. A person taking a statin is advised to report muscle weakness, tenderness or pain to their doctor promptly. The risk of muscle pain and weakness is increased if a statin is taken with gemfibrozil (Lopid), ciclosporin (Neoral / Sandimmun) or nicotinic acid. Kidney and liver function should be closely monitored if these drugs are taken with a statin.

Most statins are metabolised in the liver in a similar way to the protease inhibitors, primarily using the P450 CYP3A4 pathway. Some protease inhibitors cause substantial and potentially dangerous increases in blood levels of statins, increasing the risk of muscle damage. Drug interaction studies in HIV-negative participants found large increases in atorvastatin and simvastatin levels when dosed with saquinavir and ritonavir. However, the decline in pravastatin levels was less pronounced, indicating this may be the safest statin for use with protease inhibitors.1 Another study has recommended that simvastatin not be taken with nelfinavir due to a drug interaction, and that caution should be exercised when nelfinavir and atorvastatin are co-administered. Similarly, efavirenz can cause reduced exposure to simvastatin, pravastatin and atorvastatin, possibly requiring higher doses to maintain the drugs' lipid-lowering actions. 2

To date there is no evidence that taking the statins undermines the antiretroviral effect of protease inhibitors. The Chelsea and Westminster Hospital in London is conducting a study investigating the effect of pravastatin for individuals with protease inhibitor-related high lipids. However, as described above, taking both protease inhibitors and statins may increase the risk of side-effects such as muscle pain and weakness. Atorvastatin or pravastatin, which have less of an effect on the P450 CYP3A4 pathway, or a fibrate such as gemfibrozil may be the best alternatives from this perspective, although recent findings have cast doubt on whether pravastatin is effective at reducing cholesterol levels in patients taking protease inhibitors. 3

Several studies have found improvements in cholesterol and triglyceride levels after six months treatment with pravastatin, although cholesterol did not normalise when baseline levels were very high. 4 5 6 7

A team from London's Chelsea and Westminster hospital has presented data suggesting that atorvastatin is somewhat more effective than pravastatin at controlling LDL levels in people on both PI- and NNRTI-based antiretroviral therapy.

In contrast to other members of the drug class, rosuvastatin is not metabolised by the P450 pathway. A pilot study has shown that it is a safe and effective treatment for increased cholesterol and triglycerides in patients taking protease inhibitors. 8

Other drugs can also interact with the statins. For example, when fluvastatin is taken concurrently with fluconazole (Diflucan), levels of fluvastatin are elevated and exposure is prolonged.

A small proof-of-concept study has suggested that statins may also have a direct antiretroviral activity, through their inhibition of the enzyme Rho guanosine triphosphatase.9 However, this finding requires verification in clinical studies.

Similarly, some doctors have expressed concern that statins may affect the levels of immune system cells and chemical messengers or 'cytokines', potentially altering the course of HIV disease or therapy. Despite their beneficial effects on lipid levels, they warn that more research is needed to establish whether the drugs have long-term effects on the immune system. 10

United States guidelines on the management of metabolic disorders in HIV infection propose that elevated cholesterol levels should be treated with either of these two options:

  • Pravastatin (20 to 40mg daily as a starting dose).
  • Atorvastatin (10mg daily as a starting dose).

The guidelines also suggest other options to the two recommended statins, noting that fluvostatin (20 to 40mg daily) is a "reasonable alternative". They add that if statins cannot be used, for example due to drug-drug interactions, then another class of drugs, fibrates, might be considered.

Some doctors argue that since clinical trials in HIV-negative people show that it can take five or six years of statin treatment before any clinical benefit becomes evident, younger people with moderately elevated lipids but no other risk factors should be encouraged to begin statin treatment.

The latest BHIVA guidelines place their focus squarely on the possible interactions between statins and PIs. They agree with the US guidelines that the use of simvastatin and lovastatin in people on PI- or delavirdine-containing HAART is not recommended.

  • Atorvastatin levels could be doubled in people on PIs, but both suggest that this drug can be used with caution.
  • Pravastatin appears to be safe with PIs, but whereas the UK guidelines say it appears to have a low likelihood of PI interactions, the US guidelines caution that pravastatin may need to be increased when taken along with ritonavir-containing regimens.
  • Fluvastatin does not appear to have any PI-related drug-drug interactions.
  • Any of the statins are probably safe in efavirenz or nevirapine-containing regimens.
  • The US guidelines also suggest that levels of fibrates may be reduced in ritonavir-containing regimens, but otherwise no interactions are known at this time.


  1. Fichtenbaum CJ et al. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG study A5047. AIDS 16: 569-577, 2002
  2. Gerber JG et al. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin and pravastatin. Results of AIDS Clinical Trials Group 5108 Study. J Acquir Immune Defic Syndr 39: 307-312, 2005
  3. Mallon P et al. A randomised, placebo-controlled trial of pravastatin for the treatment of protease inhibitor-induced hypercholesterolaemia in HIV-infected men. Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract TuPe2, 2005
  4. Moyle GJ Mitochondrial toxicity hypothesis for lipoatrophy: a refutation. AIDS 15: 413-428, 2001
  5. Moyle GJ et al. Dietary advice with or without pravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy. AIDS 15: 1503-1508, 2001b
  6. Baldini F et al. Efficacy and tolerability of pravastatin for the treatment of HIV-1 protease inhibitor-associated hyperlipidaemia: a pilot study. AIDS 14: 1660-1662, 2000
  7. Negredo E et al. Impact of pravastatin on dyslipidemia induced by antiretroviral therapy. 14th International AIDS Conference, Barcelona, abstract TuPeB4518, 2002c
  8. Calza L et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS 19: 1051-1058, 2005
  9. del Real et al. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med 200: 541-547, 2004
  10. Corrales-Medina VF et al. Statins and HIV: beyond the metabolic and cardiovascular benefit. J Acquir Immune Defic Syndr 39: 503-504, 2005
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.