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November – December 2017

Examples of media coverage: 

  1. ​​​Lung cancer drug may be early clue in hunt for HIV cure – The Independent, November 30, 2017
  2. Cancer drug offers tantalising hope for HIV cure – The Guardian, November 30, 2017
  3. HIV breakthrough as cancer drug could hold secret to curing the virus – The Daily Mirror, December 1, 2017
  4. Bristol-Myers Cancer Drug Opdivo Shows Surprising HIV Impact – Bloomberg News, December 1, 2017
  5. HIV Cure? Lung Cancer Drugs ‘Shock and Kill’ HIV in French Patient – Newsweek, December 1, 2017

Original source(s):

  1. Scientific journal letter: Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer – Annals of Oncology, December 1, 2017
  2. European Society for Medical Oncology Press Release: Cancer drug leads to ‘drastic decrease’ in HIV infection in lung cancer patient – November 30, 2017

TAG’s commentary:
This story relates to a published case report about an HIV+ individual who received a new type of immunotherapy to treat his lung cancer. Because there is just one person involved, no conclusions can be drawn from the results – this important point is made by several scienists who are quoted in the media coverage.

The individual in question is reported to have experienced a reduction in levels of HIV DNA in their bloodstream when they were measured 120 days after starting the immunotherapy. HIV DNA levels are a rough measurement of the HIV reservoir that persists despite antiretroviral therapy (ART). The HIV reservoir is considered the major barrier to achieving a cure, and there is a lot of research into approaches that might reduce the reservoir size.

The decrease in HIV DNA levels was from 369 copies per million cells to 30 copies per millions cells, which is an approximately 92% reduction. The individual has remained on ART the whole time.

The case was orginally reported in a poster at the IAS 2017 conference this past July, and–importantly–the poster also describes a second HIV+ individual who received the same immunotherapy and saw a slight increase in HIV DNA levels measured after 30 days (this second individual is mentioned in the press release and several of the media articles, and was described in a published letter in the journal AIDS in April 2017).

At the HIV Cure and Cancer Forum that took place immediately ahead of the IAS 2017 conference, Tim Henrich also described three HIV+ individuals who had received the same type of cancer immunoterapy and did not experience any consistent changes in HIV DNA levels (see abstract OA3-1 in the Forum’s abstract book). So while this newly published case report has now drawn considerable media coverage, the individual appears to represent an outlier (at least based on information available so far).

A 92% reduction in HIV DNA levels is larger than has been reported with any other interventions except for stem cell transplants for cancers (which can only be used in severe life-threatening cancers because there is a 20-30% risk of death). The largest reduction in HIV DNA that had been described previously was around 67–84% in subset of four people participating in a clinical trial of panobinostat, a cancer drug belonging to the HDAC inhibitor class. Notably, this reduction was only associated with a slight delay in HIV viral load rebound when ART was interrupted.

Studies using an approach called mathematical modelling have suggested that a reduction in the HIV reservoir of more than 99.99% would be needed to have a chance of preventing HIV viral load rebound for life. It has also been reported that only clinical trials involving between 40 and 150 HIV+ individuals can “reliably estimate the reservoir-reducing potential of a new therapy,” which underscores the difficulty of trying to understand a result obtained in one person.

The cancer immunotherapy given to the individual in the case report was nivolumab (brand name Opdivo). Nivolumab is an antibody that targets PD-1, a receptor that can appear on the surface of T cells that have become exhausted and dysfuctional. Blocking PD-1 with nivolumab can revive the anti-cancer activity of T cells, and this is thought to contribute to significant efficacy in treating a number of different cancers.

Studies have also reported that blocking PD-1 can revive T cells targeting HIV in a laboratory dish, as well as potentially stimulating virus production by the HIV reservoir (making the reservoir vulnerable to T cell attack). The authors of the new case report suggest that this dual mechanism may explain the reduction in HIV DNA levels that they observed.

The main problem with nivolumab and similar anti-cancer immunotherapies (known as immune checkpoint inhibitors) is that they can also stimulate T cells that recognize body tissues, causing autoimmunity (see the warning and precautions on the nivolumab label). This is why they are currently being almost exclusively studied in HIV+ individuals who need immune checkpoint inhibitor treatment for cancers. Only one current trial is evaluating an anti-PD1 antibody in HIV+ people without cancer, and it is administering just a single dose.

Results from the ongoing trials of immune checkpoint inhibitors in HIV+ individuals with cancers are likely to start being reported next year. Those results will provide a clearer picture of any effects on the HIV reservoir, and should reveal if there are lessons that can be learned to help develop an HIV cure.

Amongst the media coverage, The Independent in the UK offers the most realistic headline: “Lung cancer drug may be early clue in hunt for HIV cure.” Tim Henrich’s presentation regarding three HIV+ recipients of anti-PD1 antibodies who did not experience HIV DNA declines does not appear to be mentioned in any of the articles. The worst mistake appears to belong to The Daily Mirror, whose article erroneously states that nivolumab “has no known side effects.”

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