Clinical Scorecard: Long-term HIV Viral Suppression Achieved with Co-formulated Tenofovir Disoproxil Fumarate, Lamivudine, and Dolutegravir in a Patient with Transmitted Resistance to Dolutegravir and Lamivudine: Insights from HPTN 083 Case Study

At a Glance

Key Highlights

• Transmitted INSTI resistance is rare but can occur in ART-naïve individuals without prior INSTI exposure.
• A patient with transmitted multi-class resistance including major INSTI mutations achieved sustained viral suppression on TLD (tenofovir disoproxil fumarate, lamivudine, dolutegravir) for over 3 years.
• Pharmacologic drug levels of dolutegravir were sufficient to overcome resistance mutations G140S and Q148H, supporting the efficacy of TLD despite predicted resistance.

Guideline-Based Recommendations

Diagnosis

• Perform HIV genotyping at diagnosis when feasible to detect transmitted drug resistance, including INSTI resistance mutations.
• Use next-generation sequencing assays for sensitive detection of resistance-associated mutations.

Management

• Initiate ART promptly after HIV diagnosis, even in the presence of transmitted resistance, with regimens including dolutegravir, lamivudine, and tenofovir disoproxil fumarate.
• Consider pharmacologic monitoring to ensure adequate drug concentrations to overcome resistance.

Monitoring & Follow-up

• Monitor HIV viral load regularly to assess treatment response and confirm sustained viral suppression.
• Use single-genome sequencing to track persistence of resistance mutations during therapy if clinically indicated.

Risks

• Transmitted multi-class resistance may reduce susceptibility to standard ART regimens.
• Poor adherence can lead to suboptimal drug levels and risk of treatment failure.

Patient & Prescribing Data

ART-naïve individuals with newly diagnosed HIV infection, including those with transmitted INSTI resistance.

Despite high-level genotypic resistance to dolutegravir and lamivudine, sustained viral suppression was achieved with TLD regimen due to sufficient dolutegravir drug levels overcoming resistance mutations.

Clinical Best Practices

• Early initiation of ART with potent INSTI-based regimens is effective even in cases of transmitted INSTI resistance.
• Incorporate resistance testing and pharmacologic drug level monitoring to guide personalized HIV treatment.
• Maintain adherence counseling to ensure consistent drug exposure and prevent treatment failure.
• Use comprehensive genotyping including integrase region to detect transmitted resistance mutations.

References

• HPTN 083 Trial ClinicalTrials.gov
• HPTN 083 Trial Results and Safety Monitoring
• Surveillance of Transmitted Drug Resistance Mutations