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HIV and Pulmonary Hypertension: What’s the Connection?

Posted on July 21, 2022
Medically reviewed by
Steven C. Pugliese, M.D.
Article written by
Ashley Knox

If you’re living with pulmonary hypertension (PH), you may be wondering whether the condition is connected with any other chronic diseases. One condition that scientists believe has a link to PH is human immunodeficiency virus (HIV).

Read on to learn more about the connection between these conditions and why people with HIV have a higher risk of developing PH.

Connecting Pulmonary Hypertension With HIV

Pulmonary hypertension — high blood pressure in the lungs due to any cause — affects an estimated 1 percent of people worldwide.

The risk of developing PH increases in people infected with HIV. Researchers estimate that in developed countries, up to 0.5 percent of hospitalized people with HIV also have PH. Compared with the general population, people who have HIV are 6 to 12 times more likely to develop PH that is idiopathic (of unknown cause), according to the Pulmonary Hypertension Association.

Though it’s clear that HIV and PH are connected, scientists are still researching this link.

Pulmonary Hypertension: A Disease of the Heart and Lungs

There are five types of pulmonary hypertension, based on different causes of the condition. The World Health Organization (WHO) has defined the types as:

  • Group 1 — Called pulmonary arterial hypertension (PAH), this type is caused by the narrowing of the arteries that lead to the lungs (pulmonary arteries).
  • Group 2 — The most common form of PH, PH due to left heart disease relates to problems with the valves on the left side of the heart.
  • Group 3 — PH due to lung disease is caused by chronic lung disease (chronic obstructive pulmonary disease, emphysema, interstitial lung disease, or pulmonary fibrosis) or low levels of oxygen (hypoxia).
  • Group 4 — PH due to chronic blood clots in the lungs, or chronic thromboembolic pulmonary hypertension, can happen when a person’s body is not able to dissolve a blood clot in the lungs.
  • Group 5 — PH due to unknown causes stems from other diseases, including sarcoidosis, certain anemias, and certain metabolic disorders, that are related to PH. Researchers are investigating the connection.

Symptoms of pulmonary hypertension include:

  • Shortness of breath (dyspnea)
  • Chest pain
  • Fatigue
  • Skin discoloration (such as pale gray or blue, depending on skin tone)
  • Swelling
  • Cognitive changes

Some people may have no symptoms.

HIV Infection: A Risk Factor for PH

HIV specifically infects and destroys important cells in the immune system called T cells (a type of white blood cell called T lymphocytes). As HIV progresses and T-cell count decreases, the immune system cannot fight back against other dangerous viruses and bacteria.

The condition that can result from HIV suppressing the immune system is called AIDS. People with HIV/AIDS have a weakened immune system, which can lead to other life-threatening infections if untreated. HIV-positive people are also at an increased risk of cardiovascular disease and pulmonary diseases, such as PH.

According to a study from the journal Circulation, the first report of a person with both PH and HIV occurred in 1987, when HIV was rapidly spreading throughout the U.S.

Exploring the Link Between PH and HIV

Scientists are still working to understand the role of HIV in pulmonary hypertension. Researchers have found that HIV does not infect the cells that make up the heart, lungs, and pulmonary arteries. Therefore, HIV-related damage to the lungs and pulmonary arteries is believed to be indirect.

HIV cannot infect the lungs and pulmonary arteries, but proteins made by the virus can travel through the body and cause changes that disrupt normal blood flow to the lungs. These proteins may be taken up by cells and lead to the activation of signals that change how the cells grow.

The viral proteins that may contribute to the development of PAH include glycoprotein 120 and the transactivator of transcription (Tat) and Nef proteins.

Glycoprotein 120

Glycoprotein 120 is one of the proteins that make up the outer layer of HIV and is responsible for getting the virus into human cells. Studies show exposure to this protein triggers cells to grow differently, which can lead to vascular remodeling and restriction of the pulmonary arteries.

Transactivator of Transcription Protein

The HIV Tat protein increases the expression of HIV genes. The Tat protein can be found in cells that make up the lung blood vessels and, like glycoprotein 120, contributes to the remodeling of blood vessels.

Nef Protein

Nef is an HIV protein critical to the life cycle of the virus. Studies show that the HIV-1 Nef protein can cause abnormal growth in the lung arteries called plexiform lesions, which block blood flow and contribute to pulmonary hypertension.

Other Factors Contributing to HIV-PH

A risk factor for contracting HIV is intravenous drug use — shared needles can spread the virus from an infected person to someone else. The Centers for Disease Control (CDC) reports that about 10 percent of all new HIV infections are due to drug use, and UNAIDS states that the risk of acquiring HIV is 35 times higher for people who inject drugs. Although several illegal drugs are considered possible causes of PH, studies suggest that the combination of HIV infection and drug use can increase injury and remodeling in the pulmonary arteries, leading to PH.

People with HIV are living longer due to medical advances. However, the increased longevity often comes with additional chronic diseases that can cause pulmonary hypertension. People with HIV have a high risk of developing chronic pulmonary diseases and respiratory symptoms, increasing the risk of PH due to lung disease (group 3). There is also an association between HIV infection and heart failure — specifically, left heart disease, the cause of group 2 PH.

Understanding Treatments for HIV and PH

More than 36 million people have died from AIDS-related illnesses since the start of the HIV pandemic, according to UNAIDS. Fortunately, advances in highly active antiretroviral therapy (HAART) targeting HIV have improved the survival rate and quality of life for people living with HIV. These medications disrupt the infection cycle of HIV, lowering a person’s viral load.

The role of HAART in HIV-PH is still not well understood. PH medications might change how HIV medications work or vice versa. Some studies suggest that certain antiviral medications, like ritonavir (Norvir), can further contribute to PH. Ritonavir can also change how a PH medication called sildenafil (Revatio) moves through the body. Some PH medications like bosentan (Tracleer) work well in combination with HAART.

If you are managing HIV-related pulmonary hypertension, talk with your doctor about which medications for each condition are compatible.

Find Your Team

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 46,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Are you managing HIV-associated pulmonary hypertension? Share your experience in the comments below, or start a conversation on your Activities page.

References
  1. Evaluation and Management of Pulmonary Arterial Hypertension — Respiratory Medicine
  2. Call It By the Correct Name — Pulmonary Hypertension Not Pulmonary Arterial Hypertension: Growing Recognition of the Global Health Impact for a Well-Recognized Condition and the Role of the Pulmonary Vascular Research Institute — American Journal of Physiology: Lung Cellular and Molecular Physiology
  3. Impact of Human Immunodeficiency Virus on Pulmonary Vascular Disease — Global Cardiology and Science Practice
  4. Pulmonary Disease in HIV-Infected Adults in the Era of Antiretroviral Therapy — AIDS
  5. Human Immunodeficiency Virus-Associated Pulmonary Arterial Hypertension — Circulation
  6. About Pulmonary Hypertension — Pulmonary Hypertension Association
  7. PH and HIV — Pulmonary Hypertension Association
  8. HIV: People Who Inject Drugs — Centers for Disease Control and Prevention
  9. Global HIV and AIDS Statistics — Fact Sheet — UNAIDS
  10. Injection Drug Use as a “Second Hit” in the Pathogenesis of HIV-Associated Pulmonary Hypertension — American Journal of Respiratory and Critical Care Medicine
  11. Pulmonary Disease in HIV-Infected Adults in the Era of Antiretroviral Therapy — AIDS
  12. Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study — JAMA Cardiology
  13. High Prevalence of Echocardiographic Abnormalities Among HIV-Infected Persons in the Era of Highly Active Antiretroviral Therapy — Clinical Infectious Diseases
  14. Pharmacokinetic Interactions Between Sildenafil and Saquinavir/Ritonavir — British Journal of Clinical Pharmacology
All updates must be accompanied by text or a picture.
Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Ashley Knox is a doctoral candidate at the University of Colorado, where she studies the noncoding RNAs involved in gammaherpesvirus pathogenesis. Learn more about her here.

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