Each year, 630,000 people worldwide die from HIV despite expanded access to antiretroviral therapies. Many patients enter the healthcare system with advanced HIV disease. A precise management protocol can save their lives, provided that doctors are well trained and have access to appropriate tests and treatments. With the support of L’Initiative, the Global Fund, and the World Health Organization, a team of doctors has developed a dedicated “toolkit.” David Masson, a pediatrician specializing in HIV, contributed to this initiative.
Doctor David Masson
pediatrician specializing in HIV
What is advanced HIV disease?
David Masson: Since the introduction of combination antiretroviral therapies in 1996 in more developed countries, and around 2005 in the rest of the world, people living with HIV who are on antiretroviral treatment (ARVs) can lead nearly normal lives. They are monitored, their immune systems recover, and they no longer transmit the virus. However, many patients remain unaware of their infection or have discontinued treatment for various reasons (feeling cured, fatigue, relocation, etc.).
These patients living with advanced HIV disease are at risk of developing severe illnesses. This advanced stage remains one of the last major challenges in HIV care—when they arrive at the hospital, these patients require specific treatments, in addition to ARVs, to help restore their immunity.
What is the difference in treatment for a patient with advanced HIV disease?
David Masson: Typically, the World Health Organization recommends a “test and treat” policy, meaning immediate treatment—as soon as HIV is diagnosed in a patient, ARVs should be started on the same day or within one week. This approach helps prevent patients from being lost to follow-up. They are put under treatment and closely monitored in the early stages. Their immunity improves, and they transition into routine care. In short, they adapt to the treatment, which becomes part of their daily lives.
However, when a patient presents with advanced HIV disease—as is the case for more than a third of patients diagnosed in Congo, for example—, their immunity is severely compromised, making them especially vulnerable to opportunistic diseases like tuberculosis or cryptococcosis, a fungal infection, which are the leading causes of death among people living with HIV. Cryptococcosis primarily affects immunocompromised patients, and its most severe clinical form is a life-threatening meningoencephalitis. The first priority is to treat these brain-affecting diseases, as otherwise the patient may die before the antiretrovirals have a chance to take effect.
Furthermore, these patients require specific monitoring at the start of their treatment. The initiation of antiretroviral therapy stimulates the immune system and can trigger a significant inflammatory response (immune reconstitution inflammatory syndrome). The patient may harbor dormant pathogens such as tuberculosis, cryptococcosis, or other opportunistic infections, which then reactivate in very aggressive forms as a result of the immune system “waking up.”
How is advanced HIV disease diagnosed?
David Masson: In adults, the clinical signs are often clear: cachexia (severe weight loss), skin symptoms, and neurological disorders. However, a patient can be severely immunocompromised yet shows few symptoms. With or without clinical signs, the first step is to check the levels of CD4 lymphocytes, which, to simplify, are white blood cells that orchestrate our immune response. HIV attacks these CD4 cells. [The WHO defines advanced HIV infection as a CD4 count of less than 200 cells/mm3.] Access to this test has become difficult, but today, there are rapid tests that help assess whether the patient is severely immunocompromised or not. In cases of immunosuppression, further tests are done to determine if the patient has tuberculosis, cryptococcosis, or other conditions, and these diseases are treated before starting ARVs.
Is the protocol the same for children?
David Masson: For very young children, the protocol is more delicate. First, because the pathologies associated with advanced HIV resemble those of other conditions that affect all children: bacterial infections, chronic diarrhea, respiratory infections, or malnutrition. The symptoms of HIV in young children are not the same as those in adults. Cryptococcosis is rare, and tuberculosis is difficult to diagnose. Additionally, the rapid CD4 test is not suitable in pediatrics because children’s CD4 counts are naturally much higher than those of adults. The risk is that HIV may go undetected, and when diagnosed, it may be difficult to “classify” the child. The WHO recommends considering any child under the age of 5 as being in the advanced HIV category.
Indeed, when their immune defenses are frequently low, children are at risk of rapidly developing severe forms of common illnesses, such as pneumonia or disseminated tuberculosis. A child suffering from HIV, tuberculosis, and severe malnutrition will require a more comprehensive approach, including antibiotics, oxygen therapy, rehydration, and appropriate nutrition, along with ARVs.
Does the toolkit provide details on the correct protocol to follow?
David Masson: Yes—we have gathered the protocols recommended by the WHO, along with practical documents created by other organizations (such as MSF, the Clinton Foundation, the Elizabeth Glaser Pediatric AIDS Foundation, among others) or specifically created for this purpose. In principle, an infectious disease specialist is responsible for initiating antiretroviral treatment, but more and more doctors are being trained to follow up with HIV patients, although they may not know how to recognize or manage a case of advanced HIV disease. With this “toolkit,” we provide them with a set of documents, including a summary of the necessary tests and practical guidelines for both diagnosis and treatment. Most of these documents already exist, but by bringing them together in this toolkit, we make it easier for prescribers to use them. Ideally, complementary pediatric tools should be developed.
Beyond this toolkit, what needs can health policies address?
David Masson: We hope that this document will also support advocacy efforts to encourage countries to procure rapid CD4 tests, as well as rapid diagnostic tests for tuberculosis and cryptococcosis. These rapid tests have the advantage of being accessible to any laboratory technician, even in decentralized labs, outside of hospitals. In medicine, we find what we look for—once these diseases are more widely detected, national programs will have strong reasons to request funding from the Global Fund for the appropriate treatments to better manage patients with advanced HIV disease.
