Gene Therapy for HIV Infection?

Summary and Comment |
March 5, 2014

Gene Therapy for HIV Infection?

  1. Carlos del Rio, MD

In a small, open-label study, autologous CD4 cells in which the gene encoding CCR5 had been knocked out “ex-vivo” were reinfused into patients and found to be safe.

  1. Carlos del Rio, MD

The finding that a mutation in the CCR5 gene renders CD4 cells resistant to HIV, and the apparent cure of an HIV-infected person — the “Berlin patient” — who received an allogeneic stem-cell transplant from a donor who was homozygous for the CCR5-Δ32 deletion (NEJM JW AIDS Clin Care Feb 13 2009), led investigators at the University of Pennsylvania to explore the safety of targeted genome editing in humans with HIV infection. The study was partially supported by industry.

Twelve HIV-infected patients with virologic suppression on antiretroviral therapy (ART) were enrolled — six “immune responders” with CD4 counts >450 cells/mm3 at screening and nadirs ≥300 cells/mm3 and six “nonresponders” with CD4 counts between 200 and 500 cells/mm3 at screening despite ≥2 years of ART. The patients underwent leukapheresis to collect CD4 cells, which were modified at CCR5 by a zinc-finger nuclease to render the gene permanently dysfunctional. The modified CD4 cells were then reinfused into the patients.

Total lymphocyte counts within the vascular compartment increased significantly in all patients during the first week after reinfusion, declined over the next 5 weeks, and remained stable thereafter. Patients also showed significant increases in CD4 counts (median, 448 cells/mm3 at baseline and 1517 cells/mm3 at week 1); the median increase was nonsignificantly better for immune responders than for nonresponders. In addition, CCR5-modified CD4 cells were detected in rectal-biopsy specimens.

Participants in the immune-responder group underwent a 12-week treatment interruption that started 4 weeks after the CD4-cell reinfusion. Viral load became detectable in four of the six participants 2 to 4 weeks after ART cessation. During treatment interruption, the decline in circulating CCR5-modified cells was significantly less than the decline in unmodified cells. One severe adverse reaction occurred: A patient in the nonresponder group experienced fever, chills, joint pain, and back pain within 24 hours after reinfusion.


These findings suggest that CD4 cells can be genetically modified “ex-vivo” and then reinfused safely into patients. The cells persisted, indicating that CCR5 disruption did not render them immunogenic, and they were found in the endovascular space as well as trafficking into tissues. Might genetic therapy for HIV infection be on the horizon?

Editor Disclosures at Time of Publication

  • Disclosures for Carlos del Rio, MD at time of publication Grant / research support NIH Editorial boards AIDS Research and Human Retroviruses; Journal of AIDS; Globe Public Health Leadership positions in professional societies HIV Medicine Association (Board of Directors); International AIDS Society-USA (Board of Directors)


Reader Comments (1)

Dr.S.M.Rabiul Islam Other Healthcare Professional, Orthopedics, University of Kuala-Lumpur, Royal College of Medicine, Perak.

Really its a nice topic, Late see.

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