November 2014
Examples of media coverage:
- French Scientists Find Mechanism for Spontaneous HIV Cure – Agence France-Presse, November 4, 2014
- Scientists See Mechanism for Spontaneous HIV “Cure” (Update) – Agence France-Presse, November 4, 2014
- HIV: Genetic Mutation Leads to Two Men Being “Spontaneously Cured” of Virus – International Business Times, November 4, 2014
- So-Called HIV ‘Cure’ Is Not Actually a Cure– Newsweek, November 5, 2014
Original source:
- Scientific journal article: HIV Infection en Route to Endogenization: Two Cases – Clinical Microbiology and Infection, November 4, 2014
TAG’s commentary:
Agence France-Presse launched this story onto the Internet on November 4, and it is being reposted and picked up by an increasing number of other outlets. The story relates to a scientific paper published on the same day in a little-known journal called Clinical Microbiology and Infection. The paper, authored by a group of French scientists (one of whom, Didier Raoult, is also the editor of the journal), describes two individuals who are reported to be HIV-positive but show no detectable HIV genetic material (RNA and DNA) in their blood by “standard methods.” However, the lower limit of detection for the tests used is not stated. The individuals were identified from a cohort of elite controllers, who frequently have HIV RNA levels below the limit of detection of standard viral load tests (less than 400 copies or less than 50 copies depending on the test). No testing using more recently developed ultrasensitive HIV RNA assays is reported. One of the individuals was diagnosed HIV-positive in 1985; the other was diagnosed in 2011 and is thought to have been infected for a shorter period of around 3–6 years. The researchers used “deep sequencing” techniques to find and analyze HIV DNA in blood samples from the two cases, and report that the viral DNA they found showed a significant number of mutations, which they conclude have inactivated the virus. Based on this preliminary finding, derived only from analysis of peripheral blood and not the lymphoid tissues, where the majority of HIV is known to reside, the researchers claim that both individuals are cured. In one case, CD4 T-cell and CD8 T-cell count data are presented and are normal, whereas in the other no information on these measurements is provided.
From TAG’s perspective, the data are not sufficient to justify the claim that these two cases represent cures of HIV infection and not examples of elite control. The hypermutation of HIV in elite controllers has been reported previously, although it is not a universal finding.
The authors of the paper propose an improbable-sounding theory to account for their claims, which is that HIV has become endogenous in some people, which would mean that HIV had managed to integrate into either a sperm or egg cell and then transferred to the offspring of the person in whom this integration took place. Currently, there is absolutely no evidence that this has ever happened with HIV. There are remnants of other ancient retroviruses in the human genome that have undergone this process sometime in the distant past (these are referred to as endogenous retroviruses), but no one has presented evidence that HIV has become endogenous in anybody (it would cause HIV genes to be present in every DNA-containing cell in the body). The authors also propose that the mutations they found in the HIV sequences identified in these two individuals were caused by a human enzyme, APOBEC 3G; this seems less unreasonable because the mutation-inducing activity of APOBEC 3G has been described by many scientists, and, as mentioned above, hypermutation of HIV has been reported in some elite controllers.
In sum, it is possible that something of value for HIV cure research may be learned from these cases, but a lot more information is needed. In the absence of additional information, the statement in some of the headlines that these scientists have found a mechanism for a spontaneous HIV cure is erroneous. To its great credit, Agence France-Presse has produced an update to its original story, which includes several skeptical quotes about the paper from independent scientists. Also, on November 5th, Newsweek published an article disputing the claims made in the paper, noting that the evidence presented is consistent with the two individuals being elite controllers (not cases of HIV cures).