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HIV Virologic Blips
Understanding HIV Virologic Blips

Released: June 23, 2023

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Key Takeaways
  • HIV virologic blips are isolated detectable HIV-1 RNA values in patients who previously were virologically suppressed. They may be due to patient adherence, HIV-related factors, or ART regimen‒related factors.
  • In most cases, virologic blips require no immediate changes to the ART regimen, as they often resolve spontaneously without intervention. It is crucial, however, to closely monitor HIV-1 RNA levels in the first 4 weeks following a blip to ensure that it does not evolve into sustained viremia.

For individuals living with HIV, antiretroviral therapy (ART) has been a groundbreaking treatment that suppresses replication of the virus and allows individuals to lead healthier lives. However, there are instances when the virus reappears temporarily at low levels in the bloodstream—this is known as virologic blips. Herein, we will delve into the phenomenon of virologic blips and low-level viremia, their significance, potential causes, and appropriate management strategies.

Defining Virologic Blips
Virologic blips refer to transient episodes of detectable HIV-1 RNA viremia in individuals on ART who have achieved sustained viral suppression. A blip is defined simply as an isolated HIV-1 RNA of ≥50 c/mL but <200 c/mL that later drops to <50 c/mL, whereas low-level viremia is persistent HIV-1 RNA of ≥50 c/mL but <200 c/mL. Virologic blips and low-level viremia are different from virologic failure, which is characterized by sustained viral replication with confirmed HIV-1 RNA ≥200 c/mL. 

Significance of Virologic Blips
Detecting virologic blips has become possible thanks to increasingly sensitive methods for testing HIV-1 RNA levels. Although the clinical implications of virologic blips remain a subject of debate, several studies have indicated that they do not necessarily predict treatment failure or virologic rebound. Instead, virologic blips often are considered a natural fluctuation in HIV-1 RNA levels, given the complex nature of HIV and its interaction with the immune system. 

Potential Causes
Several potential factors may contribute to the occurrence of virologic blips. Some possibilities include incomplete drug penetration into certain tissue compartments, replication of incompetent HIV, or baseline factors such as high HIV-1 RNA levels or low CD4 cell count. Transient disruptions in adherence to the ART regimen are a common possibility. Other factors—such as coexisting infections, new comedications, inflammation, or immune activation—also may play a role. In my opinion, it is also possible that secondary infection or reinfection with resistant virus can be a culprit. 

Management Strategies
The management of virologic blips depends on the clinical context and individual patient characteristics. In most cases, virologic blips require no immediate changes to the ART regimen, as they often resolve spontaneously without intervention. It is crucial, however, to closely monitor HIV-1 RNA levels in the first 4 weeks following a blip to ensure that it does not evolve into sustained viremia.

If subsequent HIV-1 RNA remains undetectable, it is generally recommended to continue the current ART regimen without modifications. If the HIV-1 RNA remains ≥50 c/mL but <200 c/mL, it is recommended to recheck at least every 3 months. However, if HIV-1 RNA rises significantly to ≥200 c/mL, further investigation is warranted to determine the cause and pursue management options that may include performing a genotype and modifying ART based on the results.

Regardless of HIV-1 RNA level, it is also prudent to assess adherence by patient report, medication refills, and pill counts, if possible. Review comedications for drug‒drug interactions and inquire about drug‒food interactions. Remember to ask about supplement intake, which is frequent among people living with HIV. Always counsel on condom use to limit risks for reinfection with ART-resistant virus. 

Case Example
I recently encountered a long-time patient whose HIV-1 RNA previously was undetectable but then began to rise, causing intermittent blips and low-level viremia. The patient requested a change in his ART despite his HIV-1 RNA remaining <100 c/mL but ≥20 c/mL. This low-level viremia made the patient very uneasy about the possibility of virologic treatment failure and risk of viral transmission.

For reassurance, at the patient’s request, I switched his single-tablet integrase strand transfer inhibitor‒based regimen to a single-tablet protease inhibitor‒based regimen. The low-level viremia persisted despite the change, and we continue to monitor HIV-1 RNA every 3 months.

Although this phenomenon can cause much angst for both healthcare professionals and patients, appropriate review, education, and reassurance are all that is typically required. In this case, it is possible that the patient is experiencing low-level viremia due to replication of incompetent HIV being harbored in HIV-1 reservoirs. 

Conclusion
Virologic blips, characterized by temporary detectable HIV-1 RNA viremia, are a common occurrence among individuals receiving ART. Although their clinical significance remains uncertain, virologic blips generally are considered a normal part of the fluctuating nature of HIV replication. Through close monitoring and appropriate management, healthcare professionals can ensure that virologic blips do not escalate into treatment failure or virologic rebound. Continued research is necessary to gain a deeper understanding of the underlying mechanisms of virologic blips and their implications for long-term HIV management.

Your Thoughts?
How often do you observe HIV virologic blips in your clinical practice? What strategies do you use to navigate these scenarios? Join the conversation by posting a comment below.