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Updated: May 6, 2026
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
In vitro and patient studies with platelets to explore off-target cardiovascular effects of integrase inhibitors
R Keniyopoullos1, A A Khawaja1, M Boffito2,3
1National Heart and Lung Institute, Imperial College London, London, UK.
Insights
Integrase strand transfer inhibitors (INSTIs) did not consistently affect platelet activation in vitro. Further research is needed to understand cardiovascular disease risks in people with HIV on these treatments.
Area of Science:
- Cardiovascular Science
- Hematology
- Infectious Disease Research
Background:
- People with HIV have a tenfold higher risk of cardiovascular disease (CVD).
- Antiretroviral treatment (ART) can have off-target cardiovascular effects.
- The impact of integrase strand transfer inhibitors (INSTIs) on platelets is not well understood.
Purpose of the Study:
- To investigate the in vitro effects of INSTIs on platelet aggregation and activation markers.
- To compare platelet activity in people with and without HIV on specific ART regimens.
Main Methods:
- In vitro treatment of platelets from individuals without HIV with bictegravir (BIC) and dolutegravir (DTG) and their combinations.
- Flow cytometry to assess platelet degranulation.
- Pilot study comparing platelet activity in people with HIV and controls.
Main Results:
- Observed changes in platelet aggregation in vitro with INSTI exposure.
- No significant effects on platelet degranulation via flow cytometry.
- Pilot study showed no significant differences but established protocols for future research.
Conclusions:
- Currently, no consistent evidence links INSTIs to platelet activation.
- Further studies with more pathophysiological relevance are warranted.
- Extensive research in people with HIV is recommended.
Introduction:
People with HIV currently face a tenfold higher risk of developing cardiovascular disease (CVD) than those without HIV. Studies have shown various off-target effects of antiretroviral treatment (ART) on the cardiovascular system, but little is known about the effects of currently used integrase strand transfer inhibitors (INSTIs) on platelets. Platelet activation is associated with increased CVD, thrombus formation, and release of proinflammatory mediators, so exploring platelet effects from currently prescribed ART may contribute to the understanding of CVD etiopathogenesis in people with HIV.
Methods:
We aimed to identify potential effects of INSTIs on platelet aggregation and activation markers from individuals without HIV after in vitro treatment with clinically relevant drug concentrations. We used bictegravir (BIC) and dolutegravir (DTG) individually or in the therapeutic drug combinations BIC/emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) or DTG/lamivudine (3TC). Additionally, we conducted a pilot study to compare platelet activity profiles from people with HIV on BIC/FTC/TAF and DTG/3TC.
Results:
Changes to in vitro platelet aggregation responses upon exposure to different INSTIs were observed both upon individual drug application and when using therapeutic combinations. However, these effects were not reflected in flow-cytometric evaluation of platelet degranulation. A pilot study in eight people with HIV and eight without HIV revealed no significant effects but established protocols for future patient studies.
Conclusion:
There is currently no consistent evidence of an effect of INSTIs on platelet activation. Further study is warranted, focusing on models with more pathophysiological relevance, including extensive studies in people with HIV.
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