Naltrexone & the HIV Pandemic

The Next Waltz
Is naltrexone the next drug to change the course of the HIV pandemic?
by Jeannie Wraight

A recent study showed one potential intervention, naltrexone, successfully promoted viral suppression in newly released ex-offenders who struggle with drug or alcohol addiction. Naltrexone may also prove effective in treating other conditions related to HIV. Twenty years of research on naltrexone show that the full potential of this drug to treat HIV patients is currently being overlooked. In connecting the dots of numerous studies on naltrexone, we see an emerging picture of one drug, used in various forms, that may be a game changer on several levels for HIV-positive people.

Two studies presented at this year’s Conference on Retrovirology and Opportunistic Infections, which were discussed at AIDS2018, found that a higher number of newly released ex-offenders who had either an alcohol or opioid use disorder remained virally suppressed six months after they were released from prison when taking extended-release naltrexone, compared to those who were not given naltrexone. Ex-offenders face numerous obstacles upon release from prison/jail. For some, addiction complicates these issues and can lead to non-retention in HIV treatment and care and a lack of adherence to ARVs.

When asked why he thought there isn’t a greater focus on naltrexone, Dr. David Malebranche, Associate Professor at the Morehouse School of Medicine, stated: “Naltrexone would be a good intervention option for HIV-positive people, particularly with the current opioid epidemic. As a medical and research community we focus on interventions such as bnAbs [broadly neutralizing antibodies], two-drug regimens, vaccines, etc., and forget about intersecting epidemics—addiction and behaviors that influence sustained engagement in HIV care. We have all this great HIV science yet if a person has mental health issues or drug addiction, we have to start there; we have to focus on what’s not as sexy and may need further studies.”

This data, combined with a separate NIH-funded study that demonstrated naltrexone’s ability to help prevent drug relapse in newly released ex-offenders, strongly calls for more studies to determine if naltrexone should be offered to people living with HIV/AIDS struggling with addiction, in order to decrease the likelihood of relapse, remain consistent in receiving treatment, and maintain viral suppression.

Naltrexone is used in several formulations including long-acting naltrexone for drug and alcohol abuse sold under the brand names ReVia and Vivitrol (among others). Naltrexone, including low-dose naltrexone (or LDN) is being studied for several uses in PLWHAs.

In 1995, Bernard Bihari, MD, discovered LDN’s effects on PLWHAs with two clinical trials which demonstrated the immunological effects of LDN on immune recombination in the early years of the HIV epidemic. The first study showed no CD4 loss in ARV-naive patients in those on LDN compared to significant CD4 loss in controls. The second study showed a substantially higher increase in CD4 cells in those who added Lodonol to their ARVs versus those on ARVs alone.

An NIH-funded study of LDN, conducted at Boston Medical Center and St. Petersburg Pavlov State University, is currently investigating the drugs effect on inflammation and pain in PLWHAs who abuse alcohol.

A Mali study published in 2011 found no AIDS-related symptoms and only a marginal CD4 decrease in ARV untreated patients on LDN. In conjunction with other studies, this study remains significant today because it shows the potential of LDN to enhance the immune system.

A study of the use of a formulation of LDN, Lodonal, in Crohn’s disease showed a significant decrease in symptoms. Data demonstrated CD4 recovery that was attributed to decreases in inflammatory cytokines. Immune Therapeutics, a small biotech company, is currently pursuing a Phase IIb/III roll-over pivotal study in people with both HIV and Crohn’s disease.Existing medications to treat inflammatory bowel diseases (IBD), such as Crohn’s disease and irritable bowel syndrome (IBS), can cause significant immune suppression which can be more damaging in PLWHAs than those with IBD alone. Lodonal is hopefully the first in a line of new therapies needed for people living with HIV and Crohn’s or IBS.

In a study conducted at the University of Minnesota, researchers discovered that naltrexone acts as a non-selective opioid receptor antagonist. Naltrexone affected HIV expression in CD4 lymphocyte cultures which play a role in the potentiation of antiretroviral drugs and suggest that clinical trials should be considered of naltrexone as an adjunctive therapy of HIV infection.

Separately, and collectively, these studies indicate that naltrexone, in its various forms, is a unique and versatile therapy that holds potential for several uses in HIV disease and other conditions. PLWHAs struggling to recover immune function and those addicted to opiates and alcohol may strongly benefit from its use and guidelines to assist these key populations of PLWHAs should be considered to help maintain viral suppression and treatment retention.

Jeannie Wraight writes the Destination: Cure column for A&U.