The three cured HIV patients: A cure for everybody

2/24/2022 5:16:34 PM

The three cured HIV patients:  A cure for everybody?


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


1.Wiseman LW. Res ipsa loquitur. West J Med. 1975 Jul;123(1):71–5.

2.Khan AN. Medical negligence: res ipsa loquitur. Med Leg J. 1985;53 ( Pt 3):164–8.

3.Wasmuth CE. The problem of Res ipsa loquitur. Ann Intern Med. 1960 Mar;52:729–32.

4.Makuku R, Seyedmirzaei H, Tantuoyir MM, Rodríguez-Román E, Albahash A, Mohamed K, et al. Exploring the application of immunotherapy against HIV infection in the setting of malignancy: A detailed review article. Int Immunopharmacol. 2022 Feb 1;105:108580.

5.Bailon L, Mothe B, Berman L, Brander C. Novel Approaches Towards a Functional Cure of HIV/AIDS. Drugs. 2020 Jun;80(9):859–68.

6.Passaes CP, Sáez-Cirión A. HIV cure research: advances and prospects. Virology. 2014 Apr;454-455:340–52.

7.Combescure C, Vallier N, Ledergerber B, Cavassini M, Furrer H, Rauch A, et al. How reliable is an undetectable viral load? HIV Med. 2009 Sep;10(8):470–6.

8.Rendina HJ, Cienfuegos-Szalay J, Talan A, Jones SS, Jimenez RH. Growing Acceptability of Undetectable = Untransmittable but Widespread Misunderstanding of Transmission Risk: Findings From a Very Large Sample of Sexual Minority Men in the United States. J Acquir Immune Defic Syndr. 2020 Mar 1;83(3):215–22.

9.Eisinger RW, Dieffenbach CW, Fauci AS. HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable. JAMA. 2019 Feb 5;321(5):451–2.

10.Gunn JKL, Patterson W, Anderson BJ, Swain C-A. Understanding the Risk of Human Immunodeficiency Virus (HIV) Virologic Failure in the Era of Undetectable Equals Untransmittable. AIDS Behav. 2021 Jul;25(7):2259–65.

11.Janssens J, Bruggemans A, Christ F, Debyser Z. Towards a Functional Cure of HIV-1: Insight Into the Chromatin Landscape of the Provirus. Front Microbiol. 2021 Mar 18;12:636642.

12.Brown TR. I am the Berlin patient: a personal reflection. AIDS Res Hum Retroviruses. 2015 Jan;31(1):2–3.

13.Ding J, Liu Y, Lai Y. Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure. Front Immunol. 2021 May 27;12:688747.

14.Stulpin C. US woman is third person to achieve sustained HIV remission after stem cell transplant [Internet]. [cited 2022 Feb 24]. Available from:

Last news

    Read more ...

    Last milstones

      Read more ...

      Last events

        Read more ...

        Last quick reads

          Read more ...

          Last other news

            Read more ...