The Importance of a Malware Free System
The integrity of the host is a critical part of the system's Trusted Computing Base. If the host system is compromised by malware, so is every Whonix virtual machine, Tor process and communication thought to be anonymous. Malware has malicious intent and can potentially: 
- View and take snapshots of the desktop.
- Peruse files and folders.
- Gain access to protected data when decrypted.
- Exfiltrate, corrupt or destroy data (particularly financial and personal information).
- Damage operating system functionality.
- Encrypt the contents of a drive(s) and demand payment for decryption (ransomware).
- Display unwanted advertising.
- Install unwanted software.
- Install persistent rootkits or backdoors.
- Track browsing and other behaviour.
- Remotely turn on webcams and microphones.
- Create "zombie" computers which form part of a botnet for spam email, DDOS attacks or the hosting of illicit / illegal material.
- Record everything a user types, sends and receives.
The Utility of Antivirus Tools
Antivirus products and personal firewalls are not drop in solutions for a secure host. Malware can often stay undetected and evade scans, while application level personal firewalls are often circumvented.  Polymorphic code and rootkits essentially render antivirus products helpless.  
Antivirus tools are actually worse than useless. In the case of sophisticated and targeted attacks, the antivirus software can serve as a pathway to exploiting a system's kernel, since they almost always run with administration level privileges.  Antivirus software also harms privacy by sending system files back to the company servers for analysis. The software also actively conducts man-in-the-middle attacks on secure SSL connections, enabling very sensitive information to be viewed. 
Preventing Malware Infections
The optimal scenario is to avoid infection by malware in the first place. Once malicious code has accessed a system, it is next to impossible to contain. Sensible steps include: hardening the operating system, carefully vetting programs and files that are retrieved from the internet, and using hypervisors (virtualizers) to isolate software that processes untrusted data.
Detecting Malware Infections
Detecting off-the-shelf (standardized) malware is a very hard problem and conceptually a lost cause. If uncustomized malware is widespread enough, then it has a chance of being detected by a technician. Tailored malware might also get detected by a technician, but the likelihood is low unless they are lucky or gifted.
Non-technical users don't have many good options. They can either:
- Spend a few years to rapidly increase their knowledge base of operating systems, network protocols, package analysis, programming, disassembly etc., and then try their luck.
- Pay exorbitant sums to a technician to try and find system malware, even though there is no certainty of success.  
- Or seek the voluntary assistance of a technician to find malware, if they are both a high value target and have a reasonable rationale for why they are likely compromised. 
Once infected with very sophisticated malware that modifies low-level firmware, it is extremely difficult to detect in almost all cases. Note this should not be confused with hardware/circuit trojans, which are malicious modifications made to machine components during the manufacturing process (though even those are not immune to detection). 
Can a virtualizer such as Qubes, VirtualBox, KVM etc. prevent hardware compromise?
Running everything inside VMs is a very reasonable approach. However, it only raises the bar and makes it more difficult / expensive to compromise the whole system. It is not a perfect solution.
No distribution of Linux (or Xen, or...) like Debian, Qubes, BSD or other variants can solve the issue of not needing to dispose of potentially infected hardware. Hardware-specific issues can really only be fixed at the hardware level. At best, software interventions can only provide workarounds.
The problem is no hardware exists that consists of entirely Libre firmware. It is very difficult to: analyze the firmware of hardware, wipe potentially compromised versions, or overwrite firmware with a most-likely-clean version. If the firmware being used was Libre Software, it would make verification easier but wouldn't stop infection. Disassembling hardware components (BIOS, disk controllers, CPU, Intel AMT etc.) and flashing them with clean versions offline is so difficult, that it is just cheaper and more convenient to buy new hardware.
Bundling undesirable anti-features like DRM in closed firmware is further evidence that Libre firmware is needed, in addition to Libre hardware designs.
- A botnet author brags in this thread of writing unbeatable malware and trolling antivirus vendors.
- The salary costs for a security researcher / malware analyst over an extended period rule this out for most individuals.
- Only a select group of people fall into this group, for instance, whistleblowers targeted and infected by tailored viruses. Experts might be located who are willing to conduct analysis pro bono; later publicizing their findings for the public benefit.
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