Track C report by Sinead Delany
This session highlighted the importance of continually advancing scientific discoveries in both treatment and prevention, and how best to translate these new scientific discoveries into affordable health programs which reach those most affected globally.
With recent advances in ART-based HIV prevention, Dr Nelly Mugo argued that successful prevention programmes will need to focus on targeting interventions to those most at risk, prioritising interventions that are most appropriate for that population, and ensuring that evidence- informed interventions are delivered in combination to achieve maximal coverage of programmes. Populations at risk will vary by setting and will need programmes tailored to their specific vulnerabilities. ART-based prevention interventions are powerful, but will only be successful if adherence is high. Unlike treatment as prevention, she argued that PrEP should not be considered lifelong but rather for “a season” or life-stage or season e.g. adolescence, couples trying to conceive, in conflict zones. Adherence is critical for the success of all ART-based prevention, and is dependent on a realistic perception of HIV risk in those using these interventions. Delivery of these interventions will not be without challenges. HIV counselling and testing is an important entry point for prevention interventions, and efforts need to be invested in optimising linkage to prevention and care. Community partnership is essential in delivery of these interventions to ensure maximal uptake and coverage. Innovations like home-based testing, point of care CD4+, and community delivery of ART will improve testing and linkage to care.
Track B report by Dr. Juergen Rockstroh
Plenary Session. TUPL01 Challenges and solutions
During this Plenary Session, Javier Martinez-Picado from Spain summarized in an excellent overview the current HIV cure agenda. Starting with the current challenges around residual replication and the greater persistent HIV burden in tissues he outlined how HIV latency is maintained and preserved in T-cells. Subsequently two possible cure models were introduced: either eradication (sterilizing cure) or remission (functional cure). Current strategies under evaluation are gene therapy, treatment optimization and intensification (to eliminate all replication), reversal of latency, immune-based therapies and therapeutic vaccination. He highlighted the global scientific strategy “Towards an HIV Cure” which was launched on 19 July 2012 as a promising initiative to unite forces to reach HIV cure but also emphasized the next important steps towards improving the cure agenda including a review of basic science to better understand the cellular, viral and immunological mechanisms that control HIV persistence as well as the development of new assays and experimental models to tackle viral reservoirs and to investigate new therapeutic agents and immunological strategies to achieve viral remission in absence of cART.
The second plenary was given by Nelly Mugo from Kenya on the implementation of the new prevention tools into clinical practice. In a very thoughtful overview she outlined that indeed for the first time, we can begin to visualize a future free from HIV/AIDS as a feasible goal. She provided a clear road map how HIV prevention could be delivered to reach the best possible outcome. This included thinking of the populations for targeted interventions (the importance of youth as a key target population was underlined), to prioritize interventions that work and finally to deliver prevention tools in combination and with high coverage.
In the third plenary Berhard Schwartländer from UNAIDS in a highly applauded presentation laid out what is needed to turn the tide in the HIV epidemic. He clearly stated that additional resources are needed to effectively further reduce the number of new HIV infections and introduced several concepts how this could be achieved. Highlighting that the economic growth is rapidly changing the world order also allowing thinking of greater funds attributed to health and HIV/AIDS in particular but also implementing different taxes such as an airline levy or a mobile phone levy. He ended with a Chinese proverb which says “Those that say it can’t be done should get out of the way of those doing it”.
Track A report by Galit Alter
Dr. Javier Martinez-Picado, a leader in the field of HIV reservoirs and cure, presented a comprehensive review of the state of the field. Despite major advances in the number of therapeutics available for the chronic suppression of HIV, patients living on ART exhibit increased mortality and risk to development of a number of chronic inflammatory conditions such as bone loss, cardiovascular complications, etc., likely related to viral persistence, and transient re-emergence from viral reservoirs. These viral reservoirs persist in many forms including resting CD4+ T cells that are not actively replicating, and therefore maintaining the virus in a latent form, as well as in long lived immune cells such as macrophages and dendritic cells, that both once in a while may become active and allow for the emergence of transient blips of virus that drive chronic inflammatory responses. Thus efforts aimed at eliminating the viral reservoir permanently may have critical health implications on the world’s HIV-infected patient population, and important health economic benefits. Central to “curing” HIV is the identification of the methodologies to monitor viral replication below the current limits of detection, the definition of the long lived viral reservoirs, mechanisms by which to reactivate these cells, and to define the mechanism of viral latency. Importantly, it is thought that viral replication may continue unabated in tissues (lymph nodes, gut, etc), either due to low drug penetration or due to the presence of large numbers of infected cells. So the fundamental question pertains to the identification of how the virus may be resurrected from viral reservoirs, marking infected cells, that can then be actively eliminated. Interestingly, viral latency is maintained by modifications to the viral genome in DNA form, either due histone acetylation, that locks the viral genome in a poorly accessible structure that cannot be transcribed. However, many new therapeutics have been identified that are able to “unlock” this conformational DNA change, allowing the cells transcriptional machinery access to the viral genome. These compounds are called histone deacetylases (HDAC inhibitors), and 2 trials, one in the US and one in Australia, have now been conducted using these compounds in ART treated patients. Preliminary data from US shows a 5-fold increase in HIV expression after treatment, without side effects, strongly suggesting that the reservoirs can be resurrected. In addition, cytokine based and disulfiram based purging mechanisms are being explored as alternate mechanisms of bringing the virus out of latency. Now interventions aimed at inducing immunity, through vaccination, will be needed to eliminate these cells, that together with reservoir purging will have great promise to finally purging the reservoir. Finally, the first evidence of a “cure” was observed in the “Berlin patient” that received a bone marrow transplant with a CCR4-delta32 donor cells following myoablative therapy. The patient has maintain undetectable viral loads, suggesting that removing the HIV co-receptor on target cells may provide a means by which to prevent viral propagation in vitro. New cost-effective strategies using zinc-finger gene therapeutic directed mutagenesis are now being explored to direct this type of modification to hematopoietic cells to try to recapitulate this protective “cure” as a potential novel means by which to beat the virus. Thus, together these approaches offer a road-map towards an HIV cure, offering new hope for all those infected with HIV globally.