HIV Cure Assessment: Undetectable Viral Load and Negative Antibody Test
A person with HIV who achieves an undetectable viral load and subsequently tests negative on antibody testing is not considered cured of HIV infection. While these findings represent excellent viral suppression, they do not indicate eradication of the virus from the body 1.
Understanding HIV Viral Suppression vs. Cure
Viral Suppression
- Antiretroviral therapy (ART) can reduce HIV viral load to undetectable levels (<50 copies/mL)
- This represents successful treatment but not viral eradication 1
- Viral suppression prevents HIV transmission and allows immune recovery
- However, HIV persists in latent reservoirs throughout the body
Antibody Response Changes
- HIV antibody levels can decline during long-term suppressive ART 2
- Lower antibody levels may reflect reduced antigen production and viral replication
- In some cases, especially with early treatment initiation, antibody tests may become negative (seroreversion) 3
- This phenomenon is more common in vertically infected children who started treatment early
Why This Is Not a Cure
Latent Reservoirs Persist: HIV integrates into the DNA of CD4+ T cells and establishes latent reservoirs that remain undetectable by standard viral load testing 1
Viral Rebound Risk: Discontinuation of ART almost universally leads to viral rebound, even in patients with undetectable viral loads and negative antibody tests 1
Current Definition of Cure: According to the International Antiviral Society-USA, a true cure would require either:
- Functional cure: Control of infection without therapy and without immune activation/inflammation
- Eradication cure: Complete purging of all replication-competent virus 1
Clinical Implications
Monitoring Recommendations
- Continue ART indefinitely despite undetectable viral load and negative antibody test 1
- Maintain regular viral load monitoring every 3-4 months 1
- CD4 count monitoring can be reduced to every 6 months once counts are above 250 cells/μL for at least 1 year 1
Patient Counseling
- Explain that undetectable viral load means untransmittable virus (U=U) but not cure
- Emphasize the importance of continued ART adherence
- Discuss that stopping ART would likely result in viral rebound and renewed risk of transmission
Research Perspectives
Current cure research strategies include:
- "Shock and kill" approaches to reactivate latent virus and purge reservoirs
- Gene therapy approaches (modifying CCR5 or provirus)
- Immune enhancement through therapeutic vaccines 1
Conclusion
While achieving an undetectable viral load and negative antibody test represents excellent treatment success, it does not constitute a cure for HIV. Continued ART is essential to maintain viral suppression and prevent disease progression.