Study Findings Suggestive of Second HIV Cure Case: The London Patient

A British man, known as the London patient, may be the second person to be cured of HIV, according to a case report published in the Lancet HIV and presented at the virtual Conference on Retroviruses and Opportunistic Infections, held between March 8 and March 11, 2020.^1,2 The London patient, who recently revealed himself to the New York Times as Adam Castillejo,³ was diagnosed with Hodgkin disease and received a stem cell transplant from a donor who carried a mutation in the CCR5 gene (CCR5Δ32/Δ32). After transplantation and cessation of antiretroviral therapy (ART), researchers reported that the patient’s plasma HIV RNA has remained undetectable for 30 months.

Although remission was reported at 18 months after ART interruption in a previous study,⁴ this study provides longer-term data for the London patient, including sampling from diverse HIV-1 reservoir sites other than blood, and provides a modeling analysis to predict the chance of viral reemergence.¹

Results showed no detectable virus in plasma, cerebrospinal fluid, semen, intestinal tissue, or lymphoid tissue. At 27 months, HIV-1-specific CD4 and CD8 T-cell responses also remained below detection, in contrast to maintenance of cytomegalovirus-specific responses. Similar to the Berlin patient,⁵ highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient.

A mathematic model to predict the probability of cure was used because it was not possible to measure the percentage of cells derived from the donor’s stem cells in all parts of the patient’s body. The model suggested that the probability of remission for life (cure) was 98% in the context of 80% donor chimerism in total HIV target cells, and greater than 99% probability of cure with 90% donor chimerism. “Based on the London patient having greater than 90% chimerism in circulating T cells, [the investigators] concluded that the chance of future viral rebound while off ART is negligible,” noted Jennifer M. Zerbato, PhD, and Sharon R. Lewin, PhD, both from the Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Australia, in an editorial commentary.⁶

Dr Zerbato and Dr Lewin further highlighted that because most “most virus that persists on ART is defective and unable to replicate, and we are able to better quantify intact and defective virus with either near full-length sequencing or [polymerase chain reaction]-based assays…a cure for HIV might be better defined as no intact virus, rather than no detectable virus.”

Because the London patient is only the second recorded HIV cure after CCR5Δ32/Δ32 allogeneic hemopoietic stem-cell transplantation, researchers plan to do viral load testing twice a year up to 60 months after ART interruption before testing yearly to 120 months. However, to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication, “more than a handful of patients cured of HIV” will be needed, as noted by Dr Zerbato and Dr Lewin.^[6] Although the London patient has been in HIV remission for 2.5 years, only time will tell whether he has truly been cured.

In addition, despite showing that “CCR5-directed approaches can lead to long-term remission of HIV-1, several barriers remain to be overcome (eg, gene editing efficiency and robust safety data) before CCR5 gene editing can be used as a scalable cure strategy for HIV-1,” concluded the investigators.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Gupta RK, Peppa D, Hill AL, et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report [published online March 10, 2020]. Lancet HIV. doi:10.1016/S2352-3018(20)30069-2

2. Gupta, RK, Peppa D, Pace M, et al. Sustained HIV remission in the London patient: the case for HIV cure. Poster presented at: CROI 2020; March 8-11, 2020; Boston, MA. http://www.croiconference.org/sessions/sustained-hiv-remission-london-patient-case-hiv-cure. Accessed March, 17, 2020.

3. Mandavilli A. The “London patient,” cured of H.I.V., reveals his identity. New York Times. https://www.nytimes.com/2020/03/09/health/hiv-aids-london-patient-castillejo.html. Published March 9, 2020. Accessed March 21, 2020.

4. Gupta RK, Abdul-Jawad S, McCoy LE, et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature. 2019;568(7751):244-248.

5. Yukl SA, Boritz E, Busch M, et al. Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog. 2013;9(5):e1003347.

6. Zerbato JM, Lewin SR. A cure for HIV: how would we know? [published online March 9, 2020]. Lancet HIV. doi:10.1016/S2352-3018(20)30075-8