A new study, published in the Annals of Oncology, shows a drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer.
Dr Andrew Freedman, Reader in Infectious Diseases & Honorary Consultant Physician, Cardiff University, said:
“The authors report the effect on the ‘HIV reservoir’ of injections of a monoclonal anti-PD1 antibody, nivolumab, given to a patient with long standing HIV to treat relapsed lung cancer. The persistence of the latent HIV reservoir in patients with HIV, well controlled on combination antiretroviral therapy (cART), is the reason why such patients currently need to continue lifelong treatment. There is much interest and ongoing research aimed at purging this reservoir, in order to develop a cure for HIV & thus allow patients to discontinue cART.
“Previous studies in animal models of HIV have suggested that anti-PD1 antibodies might be an effective strategy. The results in this one patient do indeed demonstrate an impressive reduction in the latent HIV reservoir, sustained over a period of 120 days, together with boosting of the patient’s own immune response to the virus. However, as the authors point out, it is much too early to conclude that such treatment will prove useful in the search for a HIV cure. The same investigators have published details of a second patient in whom nivolumab showed no such benefit. These two patients were included in a series of 12 patients with HIV and lung cancer given this agent, but results for the other 10 are not yet available. It is difficult to speculate at this stage why the second patient did not show the same response or indeed whether any of the others responded in the same way. Differences in the size of the latent reservoir or genetic differences between individuals, affecting their ability to mount immune responses to HIV might be important factors. Much larger studies will be needed to determine whether this treatment will prove safe and effective enough to be used more widely in HIV patients, with or without cancer. In addition, it is uncertain whether the HIV reservoir would over time re-establish itself once the treatment is stopped.
“Nevertheless, this is a potentially exciting finding and it is possible that nivolumab, most likely in combination with other approaches such as therapeutic vaccines, may have a role in the eventual discovery of a cure for HIV.”
Prof. Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene and Tropical Medicine (LSHTM), said:
“The caution expressed by the lead author seems balanced. This current case showed a large effect but they’ve had a previous case with no effect.
“We need larger randomised trials to see if this or similar anti-cancer drugs might have a notable effect on the HIV reservoir. Until we have such data talks of “cure” are premature, but it could lead to new approaches in dealing with HIV.”
* ‘Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer’ by Guihot et al. published in Annals of Oncology on Friday 1 December.
Declared interests
Dr Andrew Freedman: “I have no conflicts of interest to declare in relation to this report or to Bristol Myers Squibb who market nivolumab (I have received travel grants, lecture fees & sat on advisory boards for both Gilead & ViiV who market antiretrovirals, including those taken by the patient in this report, but these drugs are not pertinent here).”
Prof. Stephen Evans: No conflicts of interest.