Combination antiretroviral therapy directly targets HIV and can keep levels of the virus low in the blood, resulting in far better health outcomes for those who take these lifesaving medications. However, sometimes other conditions and complications associated with HIV infection can warrant further intervention. NIAID and other institutes at NIH support research that works toward ensuring the full health of people living with HIV.
Developing Treatments for HIV Co-Infections
Many people living with HIV acquire co-infections because of vulnerabilities in their immune systems and shared risk factors for HIV and other diseases, like illicit drug use or living in an area with a high prevalence of certain pathogens. These infections can occur even in those whose HIV is well-treated and who have strong immune function relative to people living with advanced HIV, or AIDS. The most serious infections that commonly occur alongside HIV both in the United States and around the world are viral hepatitis, including hepatitis C and hepatitis B, and tuberculosis, or TB.
As many as 5 million people living with HIV around the world also have hepatitis C virus, or HCV. HCV can be a chronic condition that can lead to life-threatening liver failure and liver cancer. Traditional interferon-based treatments have not worked as well in people also living with HIV. However, researchers led by NIAID and Gilead Sciences have developed new therapies that can cure even complicated cases of HCV without serious side effects. Read more about the path to a cure for hepatitis in people with HIV to learn how these discoveries were made and what they mean for people affected by these diseases.
People living with HIV are also at an increased risk of developing tuberculosis, or TB, a disease caused by the bacteria Mycobacterium tuberculosis that usually begins in the lungs. This increased risk, which can be as much as 26 to 31 times higher than someone without HIV, according to the World Health Organization—appears to persist even when HIV is well-controlled with ART. TB is the leading cause of death among people living with HIV worldwide, with most cases occurring in developing countries. Additionally, having HIV can make TB more difficult to diagnose, and medications used to treat these infections may interact negatively. In addition to efforts to address the burden of TB disease acting alone, NIAID supports research to improve TB prevention, diagnosis, and treatment in the context of HIV infection.
To that end, in 2014, NIAID researchers discovered a link between the presence of a specific immune cell in people living with HIV and a condition called immune reconstitution inflammatory syndrome (IRIS). In people with IRIS, TB causes a more severe inflammatory response, which in turn leads to more severe TB symptoms. Testing for this risk factor may help identify patients at-risk for IRIS and link them to the appropriate care.
In 2017, NIAID scientists and their collaborators developed a new diagnostic tool to rapidly identify Mycobacterium tuberculosis infections. In many parts of the world where TB is common, health care providers usually diagnose infections by identifying bacteria in sputum (a substance expelled from the lungs by coughing) using a microscope. This method requires significant time and resources, and sputum samples are difficult to collect from patients who are not actively showing TB symptoms. By contrast, the new tool, called NanoDisk-MS, chemically identifies fragments of TB-causing bacteria circulating in people’s blood. While further study is still needed, researchers found that NanoDisk-MS outperformed other diagnostic tools for TB-causing bacteria when testing blood samples from 90 people living with HIV—correctly identifying 53 of 61 patients with known TB disease and only falsely diagnosing three of the 29 participants without TB.
However, with currently available diagnostic methods, clinicians often miss many Mycobacterium tuberculosis infections in people living with HIV. These tests often fail because people living with HIV are more likely to have extra-pulmonary TB (TB that manifests outside of the lungs) or to have undetectable levels of bacteria in their sputum despite having a life-threatening infection. Attempting to address these undiagnosed TB cases, researchers in the Reducing Early Mortality and Morbidity by Empiric Tuberculosis Treatment (REMEMBER) trial tested whether they could improve survival by offering TB treatment to people living with HIV who tested negative for active TB disease. The trial enrolled 850 participants and took place in several countries where TB is common. The researchers found that, after 24 weeks, participants given TB treatment did not have an advantage over those given only preventative TB therapy, indicating that clinicians should continue to provide TB treatment only to people living with HIV who test positive for TB. Read more about the REMEMBER trial.
NIAID also supports research on opportunistic infections that can occur in cases of inadequately treated HIV. When the immune system is damaged by HIV, fungi and other pathogens that the immune system would normally clear can lead to severe infections, like pneumocystis pneumonia or cryptococcal disease, that require immediate attention. To better address these infections when they occur, NIAID supports research to find the best practices for diagnosing and treating these conditions. For example, an ongoing clinical trial called C-ASSERT is investigating whether a drug originally developed for depression can reduce mortality from Cryptococcal meningitis in people living with HIV. Read more about C-ASSERT.
Managing Non-Infectious Complications of HIV
The introduction of antiretroviral therapy (ART) and other treatment advances have transformed HIV care and the direction of treatment research over the past several decades. At the beginning of the HIV/AIDS pandemic in the 1980s, people often succumbed to opportunistic infections within years or even months of an AIDS diagnosis. Today, an individual diagnosed with HIV can expect to live to a nearly normal lifespan with consistent use of current HIV medications. As more people living with HIV progress through their fifties, sixties, and beyond, the medical community continues to learn more about how cardiovascular disease, type II diabetes, memory problems, cancer, and other conditions associated with aging may differ in people living with HIV.
Researchers have gained insight into how HIV influences individuals’ health over time through NIAID studies that follow cohorts of people living and aging with HIV, such as the START trial, the Women’s Interagency HIV Study, and the Multicenter AIDS Cohort Study. They have found that even when HIV is well-controlled with ART, immune cells undergo persistent activation that causes chronic inflammation in organs and systems throughout the body. Because inflammation is a key driver of many age-related illnesses, people with HIV are particularly prone to these conditions as they age. Also, while HIV medications ultimately preserve health and next-generation therapies have fewer side effects, prolonged ART use has been linked to kidney abnormalities, osteoporosis, and other health problems.
Heart disease—the number one killer of men and women in the United States regardless of HIV status—is a particularly troubling complication of HIV infection. People living with HIV are 50 to 100 percent more likely to develop cardiovascular disease than people without HIV. This elevated risk is partially a result of chronic inflammation, which can harden blood vessels over time and increase one’s chances of experiencing heart attack and stroke. Additionally, some older HIV medications have side effects that can lead to high cholesterol, which can also contribute to cardiovascular disease.
To address the urgent need to prevent cardiovascular disease in people living with HIV, the National Heart, Lung, and Blood Institute and NIAID launched the Randomized Trial to Prevent Vascular Events in HIV, or REPRIEVE, in 2015. The study aims to enroll 6,500 participants between the ages of 40 and 75 in sites across the United States and abroad to determine whether a daily dose of a cholesterol-lowering statin can reduce the risk of cardiovascular disease in people living with HIV who would not normally be prescribed a statin. Researchers will also evaluate how this effect may differ for women living with HIV in an embedded study called Follow YOUR Heart. Read more about the REPRIEVE study.