Wrestling with the implications of the Mississippi case
1 August 2014. Related: Paediatric care, Cure-related research.
Richard Jefferys, TAG
Understandably, there has been extensive media coverage of the announcement on 10 July that HIV has rebounded in the “Mississippi Baby” case. [1]
Although a full discussion of the implications will take time, there are some points that may be worth noting now.
The number of individuals considered cured of HIV infection has dwindled back to one: Timothy Ray Brown. It had been hoped that the child in Mississippi was another example, and for a brief time last year two adults from Boston were considered possibly cured. In all three of these cases, the evidence suggests that HIV reservoirs were reduced to extremely low levels but eventually a dormant, latently infected cell became activated and sparked a renewal of viral replication.
Earlier this year it was reported that a second baby from Long Beach in California shows no detectable HIV after very early treatment, [2] and some media outlets erroneously portrayed this case as potentially another example of a cure, but the infant remains on antiretroviral therapy. The sobering outcome in Mississippi further emphasises that the absence of detectable HIV cannot be assumed to mean the virus has been cleared.
As highlighted by amfAR in their statement, the case underscores the challenges associated with attempting to measure the vanishingly small amounts of HIV that can persist, particularly in body tissues. [3]
The fate of the clinical trial based on the Mississippi baby, IMPAACT P1115, may become a matter of controversy. A variety of opinions are reported in the current media coverage. Some scientists note that two years without the need for treatment is not trivial and represents a benchmark to try and build upon; based on this view, it is perhaps possible that the IMPAACT trial could attempt to establish how frequently such remissions occur, and whether they might last longer in some cases (close monitoring would certainly be required during interruptions to ensure treatment could be restarted as soon as any HIV rebound was detected). But other scientists argue that interrupting treatment would now be unethical (NPR quotes an ethicist making this argument). [4] Further dialogue is clearly needed to reach agreement on how (or if) the trial should proceed.
Although the news has dealt a severe blow to hopes that very early HIV treatment alone might be curative, the evidence remains clear that swift initiation of antiretroviral therapy after infection is associated with a significant reduction in the size of the HIV reservoir. For this reason, there is still broad consensus that early-treated individuals are ideal candidates for trials of interventions that aim to further reduce the reservoir or induce containment of any residual HIV. Such trials are already being planned in a cohort of early-treated adults in Thailand, using interventions such as therapeutic vaccination and infusions of broadly neutralising antibodies (the design of the latter trial, RV397, was presented and discussed at the Regulatory Pathway for HIV Cure Research meeting). [5]
The return of the Mississippi child to the media spotlight is also a reminder that the case arose from a bad situation, in that the mother had an undiagnosed infection and did not receive necessary prenatal healthcare. Ideally, all HIV positive mothers should be able to access high quality, appropriate care to minimise the risk of perinatal transmission, and this remains a vital priority. Jim Merrell from the Prevention Justice Alliance wrote a commentary on this issue last year that is still relevant. [6]
Source: TAG basic Science Blog (11 Jul 2014)
http://tagbasicscienceproject.typepad.com/
References:
- NIH press statement. “Mississippi baby” now has detectable HIV, researchers find (10 July 2014).
http://www.niaid.nih.gov/news/newsreleases/2014/Pages/MississippiBabyHIV.aspx - Jefferys R. Reports of a second baby possibly cured of HIV: uncertainty remains. TAG basic science blog (06 March 2014).
http://tagbasicscienceproject.typepad.com/ - AmfAR. Surprising new development in “Mississippi child” case (10 July 2014).
http://www.amfar.org/Mississippi-Child-Update/ - Harris R. Mississippi child thought cured of HIV shows signs of infection,. NPR (10 July 2014).
http://www.npr.org/blogs/health/2014/07/10/330538734/mississippi-child-thought-cured-of-hiv-shows-signs-of-infection - Ananworanich J. Forum Cure Project – Session 7: Case Study of the RV397 Protocol.
https://www.youtube.com/watch?v=vJAFMdRA70o&feature=youtu.be - Merrell J. Behind the miracle cure a broken system lurks. Prevention Justice Alliance. (05 March 2013).
http://www.preventionjustice.org/behind-the-miracle-cure-a-broken-system-lurks/