Original Title: Terapia Génica para inmunicidad para VIH. Mutación CCR5-Delta 32

Authors' objectives: To assess the safety and efficacy of gene therapy, specifically, related to the CCR5-delta 32 mutation and its impact on immunogenicity in HIV infected patients.

Authors' results and conclusions: A total of 15 studies were included from the search. The impact of a CCR5-delta 32 mutation on the phenotypic manifestation of the disease is the control of the inflammatory response, and such control is associated with the progression of autoimmune and infectious diseases, making this the only genetic mutation so far known to completely block HIV-1 infection in humans. To date, very few people are considered to have been cured of HIV infection. In the case of the first, “the Berlin patient”, although traces of HIV were found in his cells, the virus did not rebound. It is likely that the transplanted cells from a CCR5-delta 32 donor protected his immune system. He also received aggressive chemotherapy, total body irradiation, and two stem cell transplants. To draw more definitive conclusions, we need to wait for the publication of more data given that the analysis of genetic studies on HIV-1 may provide potential innovative avenues for diagnosis, prediction, therapy, and prophylaxis. Conclusions Replacing an immune system carrying HIV with one resistant to HIV seems to be the key to curing this infection. The goal is to as far as possible eliminate the latent HIV reservoir including T cells that can reignite the infection in the host before being able to obtain specific immunity in vivo against this virus. And it does seem likely that a cure is only achieved in cases in which the donor´s immune system has eliminated the reservoir through a transplant from the donor resistant to HIV. There is a need for further clinical data to support the view that the therapeutic outcomes in people who receive gene therapy targeting CCR5 will provide a similar functional cure to that observed in the Berlin, London, and Düsseldorf patients.

Authors' methods: A literature review was conducted to identify syntheses of evidence on the topic of interest (assessment reports, systematic reviews/meta-analyses) in databases specialised in systematic reviews (the International HTA Database [Inahta]) and the Cochrane Library [Wiley]), as well as in general databases (Medline [PubMed] and Embase [OvidWeb]), through the use of publication type filters.

Project Status: Completed

Year Published: 2023

URL for published report: https://www.euskadi.eus/contenidos/informacion/osteba_publicacion/eu_def/adjuntos/TE_54_2018_OSTEBA_terapia-genica.pdf

English language abstract: An English language summary is available

Publication Type: Rapid Review

Country: Spain

Organisation Name: Basque Office for Health Technology Assessment

Contact Address: C/ Donostia – San Sebastián, 1 (Edificio Lakua II, 4ª planta) 01010 Vitoria - Gasteiz

Contact Name: Lorea Galnares-Cordero

Contact Email: lgalnares@bioef.eus

Copyright: <p>Osteba (Basque Office for Health Technology Assessment) Health Department of the Basque Government</p>