Durban Diary

Photo: Brent Allan, Living Positive Victoria

Calls to unite HIV positive people in the struggle to control the HIV epidemic have opened the International AIDS conference in Durban, South Africa. From grandmothers rallying to demand treatment access and recognition to discussions of psycho-social issues associated with cure research participation, the conference is set to draw plenty of international attention. From scientific developments and discussions about program funding, through to political engagement and ways to battle stigma, the conference will inform, educate and inspire. Here we present selected highlights and impressions from people on the ground in Durban, particularly focussing on HIV cure research.

International AIDS Society Towards a Cure Symposium

This symposium took place over the weekend before the main conference. A community engagement workshop preceded the symposium to encourage wider public interest in discussions and presentations around HIV cure. Issues discussed included:

• The need for accessibility of any potential HIV cure, especially within resource limited countries where roll out of antiretroviral treatment is a more pressing priority.
• Pursuing a cure for HIV does not, in itself, stop HIV stigma. HIV stigma needs to be fought with education and ongoing community engagement.
• Concerns around the language of cure: need to distinguish between a complete, sterilising cure where HIV is completely eliminated from the body, and a functional cure where treatment can be stopped but some low level of HIV remains. Some concerns expressed around the terminology of other strategies such as ‘shock and kill’ and ‘eradicate’, which apply to the virus, not the person infected.

Workshop attendee, Dr Renée van der Sluis from the Doherty Institute reflected

To hear all these stories from people reaching out to be heard and share the stories of their community was incredibly informative and sometimes even emotional. There are people that are so eagerly waiting for a cure that it puts our work as scientists in a new light.

The cure symposium itself kicked off with a clear and engaging keynote address on HIV persistence from Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases in the US. Other sessions covered the importance of community partnerships in progressing towards a cure, the role of ethics and social sciences in cure research, paediatric cure research, basic science of HIV latency, some novel strategies for achieving a cure, and the need for collaboration between biomedical and social sciences, which forms a critical part of the IAS global scientific strategy for a cure.

Here are some of the issues and findings presented during the symposium:

• How is cure defined? Is it a lack of HIV DNA? A lack of HIV RNA? The absence of anti-HIV antibodies? And where should these parameters be measured? In blood or tissue?
• Infant immune systems are fundamentally different from adult’s, an important consideration for interventions in children
• Immediate treatment is critical for infants, otherwise death will occur within 1-2 years. Treated infants do not develop anti-HIV antibodies, and will end up with a smaller HIV reservoir than most treated adults. These people are potentially a very interesting group for cure researchers.
• Thumbi Ndung’u from the University of KwaZulu-Natal presented data from a group of young South African women who were diagnosed and treated very early in HIV infection. These women never seroconverted (developed HIV antibodies), although HIV infection was detected. Their peak HIV viral loads remained low, and their CD4 counts remained relatively untouched a month after diagnosis. This study, covered here shows the potential of interventions in high risk groups in Africa.
• Andrew Badley from the Mayo Clinic spoke about a Bcl-2 antagonist which targets HIV infected cells producing viral protease. Bcl-2 regulates cell death, and targeting this protein may help clear HIV infected cells from the body.
• Giorgio Bozzi from the US National Cancer Institute presented some intriguing data from two people living with HIV on antiretroviral treatment who consented to a full tissue analysis after death. This involved looking for traces of HIV in a huge number of organs and tissues to find evidence of ongoing replication, but no evidence was found.
• Olivier Lambotte from the French Hôpital Bicêtre emphasised the lessons HIV cure researchers can take from cancer research – a theme echoed in the recent CNN editorial from Françoise Barré-Sinoussi, Sharon Lewin and Steve Deeks.
• Findings from several non-human primate studies highlighted developments in administering a PD-1 blockade (an immune checkpoint inhibitor), the impact of giving the cytokine IL-15 on immune activation and the consequence of CCR5 gene editing.
• Annemarie Wensing of the University Medical Centre in Utrecht, Netherlands presented data from the EpiStem cohort, which includes stem cell transplant recipients, some who have received cells from CCR5 delta 32 donors like the Berlin patient, Timothy Ray Brown. Preliminary results show reduction of HIV reservoirs to very low levels in these people.
• Jintanat Ananworanich from the US Military HIV Research Program presented results from a trial assessing a combination treatment (vorinostat/hydroxychloroquine/maraviroc) to flush out latent virus, followed by treatment interruption. The combination therapy did not prevent viral rebound.

Thanks to Dr Renée van der Sluis and Dr Hao Lu from the Doherty Insfor sharing their impressions. The official press release for the symposium can be read here, and a detailed program here.

Conference snapshots

Photos: Dr Renee van der Sluis

Targeting Reservoirs for a Cure

This was a basic science session on Thursday 21st July.

Dr Miles Davenport from the Kirby Institute at the University of New South Wales presented recent work modelling the patterns of HIV reactivation during treatment interruption. The researchers used ‘tagged’ virus to infect rhesus macaques, who were then given antiretroviral drugs before being taken off treatment. After looking at the ‘tags’ on the virus that re-emerged, the researchers were able to develop mathematical models of virus reactivation. Their results showed that HIV reactivation from latency occurs on average every 6 days.

Dr Kamel Khalili from Temple University in the US presented data on the use of the CRISPR/Cas9 system for removing HIV DNA from infected cells. By using a number of different models of HIV infection, Khalili and colleagues showed that their editing strategy completely removed HIV from cells. The researchers showed the effect in cells from healthy people which were infected with HIV in the lab, in cells from people living with HIV and in mouse models of infection. These results support the use of this type of gene editing for clinical trials.

Dr Christopher Peterson from the Fred Hutchinson Cancer Research Centre in Seattle, US, presented results from another gene editing strategy using enzymes called zinc finger nucleases to edit the CCR5 gene. Dr Peterson showed results from a study in pigtail macaques where blood stem cells were modified by the technique to remove CCR5. The modified cells were successfully returned to the animals, and then spread to a range of different sites in the body. The effect was limited though – there were not enough modified cells to dramatically reduce virus replication when treatment was stopped.

Dr Li Huang from Duke University Medical Center in the US presented data showing that the drug gnidimacrin (which interferes with cell signalling) can specifically kill HIV infected cells, especially when used together with another anti-latency drug TPB. While these results came from a laboratory model, they show the potential of these drugs to activate latent HIV.

clinical trial cure gene therapy HIV latency research study viral reservoir