Atorvastatin
| Evidence Level: L1 | Predicted Indications: 4 |
Table of Contents
- Atorvastatin
- Pharmacist Assessment Report
- Atorvastatin: HMG-CoA reductase inhibitor (statin) → HIV infectious disease
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Atorvastatin: HMG-CoA reductase inhibitor (statin) → HIV infectious disease
One-Sentence Summary
Atorvastatin is a statin that lowers cholesterol by inhibiting HMG-CoA reductase and is marketed in Australia as Lipitor. The TxGNN model predicts it may be relevant to HIV infectious disease, with 14 clinical trials and 20 publications compiled for this prediction. The best-supported use is managing lipid abnormalities and cardiovascular risk in people with HIV, not direct antiviral activity.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | HIV infectious disease |
| TxGNN Prediction Score | 0.9931 |
| Evidence Level | L1 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data for atorvastatin is not available in the data compiled for this report. It is a statin, and statins inhibit HMG-CoA reductase to lower LDL cholesterol. They also have anti-inflammatory and immunomodulatory effects, including reduced monocyte/macrophage activation and lower systemic inflammation markers.
These effects are relevant in HIV. People with HIV on antiretroviral therapy often have chronic immune activation, and protease inhibitors are associated with raised cholesterol and triglycerides. This increases cardiovascular risk. The supporting trials mostly target PI-associated dyslipidaemia, immune activation and inflammation, and HIV-associated neurocognitive disorder, rather than viral suppression.
Atorvastatin is metabolised by CYP3A4, and protease inhibitors and boosters (ritonavir, cobicistat) strongly inhibit this enzyme. Dose limits and monitoring are therefore needed.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01766076 | Phase 3 | Completed | 30 | Atorvastatin as adjuvant therapy in suboptimal antiretroviral responders; effect on immune activation (RCT, African cohort) |
| NCT03037372 | Phase 3 | Unknown | 320 | Atorvastatin vs rosuvastatin as adjunct to HAART; effects on immune activation, inflammation and immune ageing over 36 months |
| NCT00367458 | Phase 2 | Completed | 24 | Placebo-controlled trial in HIV-positive patients not on antiretrovirals; effects on viral load and immune activation markers |
| NCT02081638 | Phase 2 | Completed | 53 | Statin versus aspirin in elite controllers and ART-treated people with HIV; inflammation and clotting |
| NCT00663234 | Phase 1/2 | Terminated | 28 | Escalating atorvastatin doses for PI-associated raised LDL cholesterol in HIV-infected children and adolescents |
| NCT01600170 | Phase 4 | Completed | 11 | Statin modulation of monocyte/macrophage activation for HIV-associated neurocognitive disorder |
| NCT00965185 | Not applicable | Completed | 40 | Statin therapy for plaque inflammation, atherosclerosis and endothelial function in HIV |
| NCT01263938 | Phase 4 | Completed | 5 | Pilot of atorvastatin effects on monocyte activation in HAART-treated individuals |
| NCT00355251 | Phase 4 | Terminated | 5 | Atorvastatin and plasma viral replication around antiretroviral treatment interruption; too small to be informative |
| NCT00017758 | Phase 1 | Completed | 56 | Pharmacokinetic interaction of efavirenz and nelfinavir with statins (interaction data, not efficacy) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29770749 | 2018 | RCT | HIV Clin Trials | Rosuvastatin and atorvastatin preserved renal function in HIV-1-infected patients with chronic kidney disease and hyperlipidaemia |
| 37450602 | 2023 | Open-label RCT | AIDS | Atorvastatin versus aspirin in elite controllers and ART-treated people with HIV; targeting residual inflammation |
| 18991624 | 2008 | Randomised open-label study | Curr HIV Res | Rosuvastatin, pravastatin and atorvastatin for PI-associated hypercholesterolaemia (94 patients) |
| 25907504 | 2015 | Systematic review | Am J Cardiol | Usefulness of statin therapy in HIV-infected patients |
| 29804227 | 2018 | Review | Curr Infect Dis Rep | Benefits and risks of statins for cardiovascular risk reduction in HIV |
| 22770622 | 2012 | Review | Expert Opin Pharmacother | Safety and effectiveness of statins for HIV-dyslipidaemia |
| 28364370 | 2017 | Review | Am J Cardiovasc Drugs | Recommendations for managing drug interactions between statins and HIV medications |
| 23703578 | 2013 | Review | Clin Pharmacokinet | Drug interactions between statins and antiviral protease inhibitors |
| 36549898 | 2023 | Pharmacokinetic analysis | HIV Med | Atorvastatin exposure and vitamin D levels versus lipid outcomes in people with HIV |
| 41774493 | 2026 | Preclinical (mouse) | JCI Insight | Atorvastatin suppressed HIV/ART-induced cardiac fibrosis in mice by blocking platelet TGF-β1 signalling |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 13374X | Lipitor | Tablet 80 mg (as calcium) | Not recorded in the local data |
Safety Considerations
- Drug Interactions: 100 interactions were identified. The main ones listed are:
- Major: clarithromycin.
- Moderate: aprepitant, omeprazole, esomeprazole, lansoprazole, pantoprazole, cimetidine, clotrimazole, miconazole, dexamethasone, eliglustat, eluxadoline, metronidazole, naltrexone, pectin, rosuvastatin, simvastatin.
- Minor: aluminium hydroxide, magnesium hydroxide, liraglutide.
- Relevance to HIV treatment: protease inhibitors and boosters (ritonavir, cobicistat) strongly inhibit CYP3A4, raising atorvastatin exposure. Dose limits and monitoring for muscle toxicity are needed.
- Conditions of concern: the data compiled for this report flag liver failure and liver disease, kidney disease, gallbladder disease, hypothyroidism, myopathy and other muscle disease, rhabdomyolysis, and substance abuse/dependence. These are not taken from label text.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Completed Phase 3 and Phase 2 trials and several randomised studies in people with HIV support the use of atorvastatin for lipid and inflammation-related goals, and there are no completed trials showing antiviral benefit. The trials are small, and the CYP3A4 interactions with protease inhibitors are clinically important.
To proceed, the following is needed:
- Clarify the target outcome (dyslipidaemia and cardiovascular risk in people with HIV, rather than antiviral effect).
- Larger trials with clinical endpoints, since the completed trials enrolled 24 to 53 participants.
- Mechanism of action data and the TGA Product Information warnings and contraindications.
- A dosing and monitoring plan for patients taking protease inhibitors or boosters.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.