The three cured HIV patients: A cure for everybody

The three cured HIV patients:  A cure for everybody?

Highlights

1. HIV patients who adherently use antiretroviral therapy (ART) often reduce their viral loads to undetectable levels and cannot transmit the infection to their sexual partners although they are not cured.

2. A functional cure is when an HIV patient has durably silenced the latent provirus in infected cells, thereby preventing viral rebound by creating a cellular reservoir resistant to reactivation.

3. All the three functionally cured HIV cases in the literature had leukemias, and all underwent allogeneic hematopoietic stem cell transplantation (HSCT) from donors with homozygous CCR5 delta32 mutation. This further strengthens the need to develop treatment modalities targeting clearing HIV reservoirs and resistant target cells for everyone.

 The Main Text

In medical jurisprudence, Res ipsa loquitur "Latin: the thing speaks for itself" is a principle used in civil courts to relate the nature of the injury to the level of medical negligence committed when other forms of evidence are inaccessible[1,2]. Res ipsa loquitur will go on to influence a definitive court rule, which is a win-or-lose, or an all-or-nothing outcome of the nerve stimulation principle. In clinical practice and medical research, the quest to seek effective medical drugs depends not only on the designation of medical intervention, whether it was black or white, practical or not but also on quantifying the degree and duration of efficacy. Therefore, even in law, the application of Res ipsa loquitur is limited for lacking consideration into other forms of evidence[3]. 

Regardless of having effective antiretroviral treatment (ART), which has lowered all epidemiological parameters to a nadir[4], for the majority, the cure for HIV  remains a scientific challenge and elusive[5,6]. HIV patients who religiously comply with ART therapy often reach undetectable viral load levels and can not transmit the infection to their sexual partners[7–9]. As far as this is true, there is little knowledge on the percentage of individuals at a population level who sustain viral suppression long term, which leaves a certain small percentage of transmission risk, especially if viral load monitoring, adherence, and continual health education support are neglected[10]. However, literature has recorded three exceptional cases of patients medically declared HIV-free or "functionally cured." A functional cure is when an HIV patient has durably silenced the latent provirus in infected cells and thereby prevents viral rebound by creating a cellular reservoir resistant to reactivation[11]. In the context of this article, a functional cure is a clinical res ipsa loquitur, given how it defines "cure" as a state of HIV pathophysiological regression and improvement of clinical outcomes, at the expense of whether HIV is still present in the body or not.

The "Berlin patient" Timothy Ray Brown was the first person in the world to be cured of HIV[12],  followed by the "London patient"Adam Castillejo[13], and lastly, the unnamed US woman[14]. What's common among all these cases is that 1) they had leukemias, 2) they all underwent allogeneic hematopoietic stem cell transplantation (HSCT) from donors with homozygous CCR5 delta32 mutation. Do these cases imply that the protocol to get HIV cure is first to get leukemia and HIV followed by a similar HSCT? No. The issues inspire further research, especially in the potential means of clearing HIV reservoirs and resistant target cells to attain a Res ipsa loquitur functional cure for everybody.

By:Rangarirai Makuku

The UJA of Zimbabwe

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