Gene Mutations Tied to Immune Comeback during Therapy for HIV-1

Researchers with the Infectious Disease Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) here and the University of Texas at San Antonio have published a patient outcome study in the March 30 online edition of Nature Medicine that may signal a need for a change of thought in the management of HIV. The IDCRP was established in 2005 by the National Institutes of Allergy and Infectious Diseases and USU as a major new initiative to focus on clinical infectious diseases of military importance. This collaborative program encourages the exchange of scientific ideas and fosters progress in fighting new health challenges. Among the IDCRP collaborators in this program are Drs. Mathew Dolan, Brian Agan and Maj. Vince Marconi at Wilford Hall Medical Center, San Antonio.

The IDCRP is headquartered within the Department of Preventive Medicine and Biometrics (PMB) at USU. The Principal Investigator, CAPT Gerald V. Quinnan, Jr., M.D., is also the chair of PMB. According to Quinnan, “This research is another accomplishment of the IDCRP in our efforts to connect with other researchers throughout the country and bring new insights to the care and prevention of infectious diseases including HIV.”

According to the press release from University of Texas, San Antonio:

“A new study by U.S. scientists provides compelling evidence that two genes are linchpins in defining the course of immune restoration in HIV-positive individuals undergoing virus-suppressing therapy.

Nature Medicine, one of the world’s highest-impact journals, posted the study online March 30. The findings explain why some subjects’ immune systems only weakly recover T-cell counts and function, despite stunting of HIV-1 replication by highly active antiretroviral therapy (HAART), while others’ immune systems roar back.

The two genes are CCR5, an HIV-1 co-receptor, or portal of entry, for the virus into CD4+ T cells, and CCL3L1, an HIV-suppressing molecule that binds to CCR5.

“The new results suggest that we may be able to personalize the treatment of HIV as we might be able to predict, based on the presence of these gene variations, whether someone will have a better or worse immunological response when taking HAART,” said lead author Sunil K. Ahuja, M.D., professor of medicine, microbiology, infectious diseases and biochemistry at The University of Texas Health Science Center at San Antonio and director of the Veterans Administration Center for AIDS and HIV Infection at the South Texas Veterans Health Care System in San Antonio. He holds the university’s President’s Council Chair for Excellence in Medical Research.

“We categorized the copy number of the CCL3L1 gene and variations in the CCR5 gene into three categories designated as high, moderate and low genetic risk groups," said Matthew Dolan, M.D., co-lead author who also helped oversee the cohort of subjects at Wilford Hall Medical Center, San Antonio, which contributed to this study. “Those HIV-positive persons categorized into the low genetic risk group had the best recovery in CD4+ T cell counts during HAART, while those in the high rsk category had a less successful response followed by a CD4+ T cell decline.”