The Research Question
Antiretroviral therapy (ART) has dramatically reduced mortality rates from both AIDS-related and non-AIDS related diseases of people living with HIV (PLWHIV). But there are important exceptions to this trend: Certain cancers and forms of heart and liver disease remain prominent among PLWHIV. Given this concern, might a better definition of the causes of these disorders and identification of specific treatments reduce disease and mortality in these individuals?
Liver disease in ART-treated PLWHIV is often caused by nonalcoholic fatty liver disease (NAFLD). Unchecked, it can advance to an inflammatory state known as nonalcoholic steatohepatitis (NASH) and on to life-threatening conditions such as cirrhosis and liver cancer. NASH is present in about 25-30% of individuals with NAFLD. However, among PLWHIV, the proportion rises to as much as 65%. This could be because, even with ART, chronic inflammation is common in people living with HIV.
An additional concern is the aging of the HIV-positive population and increasing rates of obesity and diabetes, which are additional risk factors for NASH. The problem is even more pronounced in resource-poor countries where there are limited funds available for mass screening and diagnosis of liver disease.
To better understand these issues, scientists reviewed the epidemiology, risk factors, and therapeutic options available for NAFLD in the context of HIV. They note that although there are no treatments specific to PLWHIV, promising developments are on the horizon. One involves cenicriviroc, a drug developed to treat HIV by blocking the CCR5 receptor—a protein enabling HIV to enter cells. Cenicriviroc also prevents other immune cells from exacerbating NAFLD by blocking the cells’ entry into the liver.
Cenicriviroc is now in advanced (“Phase III”) clinical trials among HIV-negative NASH patients. If effective, it would be an ideal candidate for testing in PLWHIV. Cost-effective and widely available simple measures to screen for NAFLD, such as liver ultrasound, would be of particular benefit for resource-limited regions. This study also illuminated the lack of data on the prevalence and long-term outcome of NAFLD among women living with HIV.
The lead author of this study, Dr. Sharon Lewin, is funded by amfAR.
Dr. Laurence is amfAR’s senior scientific consultant.