TNF-alpha's Role in the Development of HIV-1 Associated Nephropathy in African-Americans

Researchers have known for years that certain HIV-positive individuals of African-American descent are at risk for a kidney condition known as HIV-1 associated nephropathy (HIVAN). This disease, which results in rapid kidney failure and may be fatal, is precipitated by the HIV infection of podocytes and renal tubular epithelial cells. Up until now it has not been known exactly how these two types of kidney epithelial cells become infected because these cells do not express the CD4 molecule, the major receptor used by HIV-1 (the most common type of HIV infection worldwide) to infect immune-system cells. A new study out of Children’s National Health System and The George Washington University Medical School, both in Washington, DC, sheds some light on the precise mechanisms involved in the development of this disease.

The scientists found that a protein called transmembrane tumor necrosis factor alpha, or tm-TNF-alpha, may be the facilitator when it comes to HIVAN. Using podocytes cultured from the urine of children with HIVAN, the team determined it was tm-TNF-alpha that enabled a low-level infection to flourish. tm-TNF-alpha is a key player in a variety of inflammatory diseases, and the study’s authors hope that the discovery of its role in the development of HIVAN will pave the way to understand how other cells that lack the CD4 receptor—such as those within a woman’s reproductive system—may encourage HIV transmission from mother to baby.

HIVAN’s greatest risk is to HIV patients who don’t receive antiretroviral therapy (ART), which has been proven quite effective in treating HIV. About 10% to 15% of both male and female African-American HIV patients who do not use ART will develop HIVAN, with more adults than children affected simply because more adults than children have HIV, according to study author Patricio Ray, MD, a professor at George Washington University School of Medicine and a nephrologist at Children’s National Medical Center. “The prevalence of HIVAN in patients receiving appropriate ART is much lower and depends on how adherent the patients are to the ART therapy,” he says. “Unfortunately, teenagers are not very adherent to the HIV therapies.”

Because of this potential lack of adherence to the medication regime, Ray recommends that all children diagnosed with HIVAN be monitored closely to ensure they’re getting the drugs they need. If not, they risk progressing to end-stage kidney disease and dialysis treatments. “Doctors should avoid the use of nephrotoxic medications,” he states, “and children can be treated with other renal therapies (i.e. angiotensin converting enzyme inhibitors) to reduce their proteinuria, treat hypertension, and prevent the progression of this renal disease.”

In addition to making sure HIVAN patients stick to their treatment regimen, Ray points out that it’s important to treat for HIVAN much earlier than before: “In the past, in adults, the presence of HIVAN was an indication to start ART even if the patients did not meet the criteria to start ART. But with [WHO’s] new approach to eradicate HIV-1 by the year 2030, all patients—adults and children—should be started on ART as soon as they are diagnosed with HIV-1.” This goes for children who acquire HIV from their mothers (the most common method of transmission), as they should be treated shortly after birth.

Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.