1. State of HIV Cure Research
Prof JG Hakim, Parirenyatwa CRS Leader
Annual Research Day; 5th May 2017

3. cure

4. ART Success Potentially 37 million need ART 18 million are on ART
ART can effectively control HIV replication
Prevents development of AIDS
Prolongs life
Reduces HIV transmission risk

5. Limitations of current ART
Operational & logistical challenges of delivering life-long ART to 37 million people
Economic cost of this strategy is unsustainable
Life long adherence is a problem
ART drug resistance is a challenge
Drug toxicities are of concern
Persistent immune dysfunction have health consequences

6. HIV Cure Definition Sterilizing cure Functional cure
Complete eradication in an individual of all replication competent HIV
Challenging to achieve
Impossible to prove
Functional cure
Long-term remission
Long-term undetectable viraemia for some as yet undefined period without ART

7. Cases of post-treatment control and remission

8. Latency Major barrier to curing HIV
Persistence of integrated viral DNA that is replication competent but transcriptionally silent.
HIV persist primarily as a latent genome in long-lived memory CD4+ T cells and to a lesser degree in naïve CD4+ T cells
Sanctuary sites
Lymph nodes, gut
Spleen, brain, genital tract, thymus
HIV persistence on ART may be influenced by;
Host genetics, age, gender, co-morbidities, co-infections, HIV disease progression state, microbiome

9. Mechanisms that maintain HIV latency in resting CD4 T+ cells
Viral blocks in latently infected cells
Integration
Epigenetic silencing
Lack of cellular transcription factors
Incomplete elongation of Transcripts
Nuclear retention of transcripts
Micro RNAs limiting of viral proteins

14. Strategies to address HIV latency
Shock and Kill
Use latency-reversing agents eg vorinostat and panobinostat
Permanently silence HIV provirus
Fully and irreversibly suppress HIV transcription-permanent silencing and lack of virus production when ART is discontinued
Enhancing capacity of the immune system to clear or control HIV
Active elimination of infected cells or control HIV persistence by T cells, antibodies, NK cells and/or macrophages
Broadly neutralizing antibodies may play a part
Therapies to reverse chronic inflammation
Enhance T cell function, reduce T cell proliferation, reduce virion production

15. Andrew Phillips
Zimbabwe

19. International AIDS Society

20. Conclusion
There is need to control the HIV virus in the absence of ART:
ie HIV cure
Considerable progress has been made in the science that will underpin HIV cure
Most studies are animal studies and phase 1 and early phase 2 studies
It is important to ensure that HIV cure approach includes other considerations:
Ethical
Social science
behavioural
There remain important knowledge gaps and research questions but there is vigorous research in this area

21. Acknowledgements Steve Deeks-slides, publications, leadership
Andrew Phillips
Antony Fauci
International AIDS Society
amfAR
Etc.
UZ-UCSF
Study Participants EC
Senior staff
Staff
Pari CRS

22. Thank You