Tremendous progress in the treatment of HIV has led to increased survival and a dramatic evolution of the disease’s course in patients. The clinical challenges confronting the population have now shifted from AIDS-related illnesses to chronic diseases, such as coronary artery disease, chronic obstructive lung disease, and chronic anemia. Multiple studies have demonstrated that the risk of developing heart, lung, and blood (HLB) disease in HIV patients is significantly higher and may be accelerated compared to the general population. In addition, the mechanisms of HIV-related HLB disease may be different because of the adverse effects of antiretroviral therapy (ART) and a greater contribution of inflammation and other factors.
According to Monica Shah, M.D., NHLBI AIDS Coordinator, the increasing burden of heart, lung, and blood diseases on this population is an important issue from both a public health and scientific standpoint, and the NHLBI is uniquely poised to take a leadership role in supporting research that addresses the new phase of the HIV epidemic. The NHLBI AIDS Program supports a robust portfolio of HIV-related grants and has recently issued a number of funding opportunities, which can be found on its website.
The Lung
The Division of Lung Diseases (DLD) also funds a number of grants studying HIV-related lung disease, including Chronic Pulmonary Obstructive Disorder (COPD) and tuberculosis in patients with HIV.
“We really don’t know a lot about the pathogenesis of lung diseases that affect people with HIV,” said Hannah Peavy, M.D., leader of NHLBI DLD’s AIDS/TB Scientific Research Group. “We know that there is an intersection between HIV and many lung diseases – such as the fact that some lung diseases, such as COPD, appear to be more frequent and to appear at an earlier age in the HIV-infected population – but we don’t really know what is driving it in terms of the basic mechanisms and we need this information to develop better treatment and prevention strategies.”
One of the collaborative lung programs, similar to the HIV-CVD Collaborative, is the Lung HIV Study. Investigators funded by this program determined that there is a greater prevalence of problems with gas exchange in the lungs in the HIV population. The ability of the lungs to transfer oxygen from the air in the alveoli to the blood is assessed by a widely used pulmonary function test called the diffusing capacity of the lung for carbon monoxide (DLCO). A decrease in diffusing capacity may indicate inflammation or damage to the lung tissue.
“It’s not exactly clear why the results in the diffusing capacity of the lung for carbon monoxide test is more frequently abnormal in the HIV-infected population,” Dr. Peavy said. “It could be because there is a lot of smoking and previous lung infections that may have affected the lung in that population. But researchers have tried to adjust for factors like smoking when evaluating results, and even after these adjustments there seems to be more of a decrease in the diffusing capacity in the HIV-infected population than in the uninfected population. The mechanisms behind why that might be happening need to be investigated.”
Dr. Alison Morris from the University of Pittsburgh Medical Center is one of the principal investigators in the Lung HIV Study. She said she feels the program has been central in helping highlight the importance of lung and pulmonary research, which hadn’t been a focal area of HIV research since the wide-spread adoption of antiretroviral therapies. These therapies led to a decrease in mortality from lung diseases such as pneumonia.
Based on some of the findings from the Lung HIV Study, DLD is now trying to encourage investigators interested in HIV-related lung disease grants to focus on understanding mechanisms of disease, and one way it’s doing so is via an RFA that it funded earlier this year. That RFA is a collaborative program consisting of eight clinical/basic site grants and a data coordinating center grant. The focus of the program is on investigating and defining cellular and molecular events underlying the pathogenesis of HIV-associated lung diseases – mostly COPD and pulmonary hypertension.
“Primary pulmonary hypertension is a rare disease in the general population, but people who have HIV have a much higher rate of pulmonary hypertension, and histologically, it looks like primary pulmonary hypertension,” Dr. Peavy said. “We don’t understand why the prevalence is higher. So one question that the researchers are looking at is: Why is it that being HIV-positive makes someone so much more susceptible to pulmonary hypertension?”
Another large HIV-related lung program is the Lung HIV Microbiome Program, which includes six clinical sites that are characterizing and analyzing changes in lung organisms in the HIV population.
“This is a very new area of research,” Dr. Peavy said. “The research is being conducted using molecular techniques instead of cultures. In the past, researchers believed that the lung was sterile, but studies have found that the lungs host lower concentrations of organisms typically found in the upper airway, which makes sense. Researchers in this program also found that, in HIV-infected people, there is an organism called Tropheryma Whipplei that is present there more frequently and in larger numbers than in HIV-uninfected people. It is surprising to find this organism in the lungs.”
T. Whipplei typically is thought of as a gut organism that is the causative agent for Whipple’s Disease, which is a rare condition that prevents the small intestines from properly absorbing nutrients. Researchers from the Lung HIV Microbiome Program published a paper about this finding earlier this year.
Dr. Morris also said she feels programs like the Lung HIV Program and the Lung HIV Microbiome Program have been key in terms of recruitment.
“These programs have resulted in increased interest in this line of research, and with the results we’re having, we’re showing it’s an important problem,” she said. “This, in turn, is helping us recruit junior investigators into the field, which is quite important in these times. There are multiple K awards and NRSAs [Ruth L. Kirschstein National Research Service Award] that have grown out of these cohorts.”
As to the future of HIV and lung research: “With all that we have learned, there are still a lot of unknowns,” Dr. Peavy said.