What is Advanced HIV Disease?

The World Health Organization (WHO) defines advanced HIV disease (AHD) as having a CD4 count of less than 200 cells/mm³ or having WHO stage 3 or 4 disease. For all children under five years who are not clinically stable receiving antiretroviral therapy (ART), AHD is diagnosed regardless of cell count or clinical status (WHO, 2024). AHD affects newly diagnosed individuals, those experiencing treatment failure and subsequent CD4 decline, and individuals re-engaging with care after treatment interruption. These groups highlight gaps across the cascade of care, reiterating the need for improvements in CD4 screening, opportunistic infection (OI) diagnosis, and linkage to optimal care.

Health worker prepares client for a blood draw to measure her CD4 count

Efforts to address AHD are crucial for improving outcomes and reducing the burden of HIV/AIDS globally. Despite significant progress, the decline in AIDS-related deaths has stagnated in recent years, threatening the global target of ending AIDS by 2030 (WHO, 2023). Up to half of the people living with HIV (PLHIV) present to care with AHD, putting them at a heightened risk of mortality even after initiating ART (WHO, 2023). This population is particularly susceptible to OIs, which further increases morbidity and mortality rates. In 2022, 630,000 people worldwide died from AHD (UNAIDS, 2023).

Common Opportunistic Infections

Opprtunistic infections (OIs) pose a significant threat to individuals with AHD, representing infections that occur more frequently or manifest more severely in those with compromised immune systems. The immune suppression associated with AHD creates an environment where opportunistic pathogens can thrive, leading to increased morbidity and mortality if left untreated (WHO, 2023). Timely identification and management of these infections are crucial for improving outcomes in individuals with AHD.

Cryptococcal Meningitis

Cryptococcal meningitis (CM), a fungal infection caused by Cryptococcus neoformans, is one of the most severe and common OIs among adults with AHD, affecting the membranes surrounding the brain and spinal cord. In 2020, 223,100 incident cases and 112,000 deaths among PLHIV were estimated, representing about 19 percent of AIDS-related mortality (Rajasingham et al, 2022). The mortality rate for CM remains significant in low-income countries, reaching 70 percent, compared to 20-30 percent in high-income settings (WHO, 2022). This disparity is largely a result of delays in diagnosis, limited access to essential diagnostic tools such as lumbar punctures and rapid diagnostic assays, and the high cost and limited availability of effective antifungal medications.

Histoplasmosis

Histoplasmosis, a systemic fungal infection caused by Histoplasma capsulatum, is a major concern for people with AHD. Disseminated histoplasmosis, a severe form affecting multiple organ systems, is associated with high mortality rates even with treatment. The high mortality rates associated with histoplasmosis, even with treatment, are exacerbated by the lack of simple and rapid diagnostic tests and relapse among people not receiving maintenance therapy (PAHO, 2020). The lack of diagnostics limits knowledge of the true disease prevalence, especially in low-resource endemic areas, where it is likely underdiagnosed due to its non-specific clinical symptoms overlapping with other diseases like TB (UNAIDS, 2022). Coinfection with TB, occurring in up to 10 percent of cases, adds to the challenges in management due to potential drug-drug interactions (UNAIDS, 2022).

Tuberculosis

Tuberculosis (TB) is the leading cause of morbidity and mortality among PLHIV with an estimated 167,000 PLHIV dying from TB in 2022 (WHO, 2023). Caused by Mycobacterium tuberculosis, TB typically affects the lungs but can involve other sites such as lymph nodes, bones, and the central nervous system. Many people are infected with latent TB but may develop active disease if their immune system becomes weakened. PLHIV are 18 times more likely to develop TB compared to individuals without HIV, highlighting the susceptibility among immunocompromised individuals (WHO, 2023). CLHIV have an especially high risk of progressing to TB disease following initial infection. Diagnosing TB in children presents additional challenges attributable to their non-specific symptoms and the difficulty in obtaining sputum samples for testing (WHO, 2023).

Severe Bacterial Infections

Severe bacterial infections (SBIs) continue to drive mortality in PLHIV and children living with HIV (CLHIV) at an alarming rate, often affecting the bloodstream, respiratory system, central nervous system, and gastrointestinal tract. SBIs can lead to sepsis and septic shock, especially if not treated early. It is estimated that SBIs account for over one-third of hospitalizations among adults and children with HIV globally; however, the exact impact of these infections on mortality and morbidity is not well-defined due to inadequate diagnostic facilities (WHO, 2024). The prevention and treatment of SBIs are further complicated by increasing antimicrobial resistance.

Frequently Asked Questions (FAQs)

General Information

What is AHD?

How is AHD different from HIV?

Why is AHD a significant concern in low- and middle-income countries (LMICs)?

Symptoms & Diagnosis

What are the symptoms of AHD?

How is AHD diagnosed?

Treatment & Management

What treatments are available for AHD?

How are OIs treated?

Where can I get more information about AHD and OIs?

AHD occurs when the immune system is severely damaged by HIV, leading to an increased susceptibility to disease progression, OIs, and death.

HIV is a virus that when left untreated or inadequately treated, can progress to AHD. AHD is characterized by a very low CD4 cell count (below 200 cells/mm³) or meeting the criteria for WHO stage 3 or 4 disease. All children younger than 5 years of age are considered to have AHD.

AHD is a significant concern in low- and middle-income countries (LMICs) because they bear a disproportionately high burden of AIDS-related deaths. This situation arises from a combination of factors, including limited access to healthcare, late diagnosis, patient loss to follow-up, and insufficient treatment options. These factors contribute to higher rates of progression to AHD and related complications.

Symptoms can vary but may include significant weight loss, chronic diarrhea, and recurrent infections. However, some individuals with AHD may be asymptomatic or mildly symptomatic despite having a very low median CD4 cell count.

Diagnosis is based on a CD4 cell count below 200 cells/mm³ or the presence of specific clinical manifestations per WHO guidelines.

The WHO recommends offering a package of interventions including screening, treatment, and prophylaxis for major OIs, rapid ART initiation, and intensified adherence support interventions.

Treatment depends on the specific infection and may include antibiotics, antifungals, antivirals, and supportive care.

To learn more about AHD and OIs, you can refer to the following resources:

Global AHD Toolkit: This comprehensive resource provides detailed information on AHD.
WHO Guidelines: The World Health Organization offers extensive guidelines on the diagnosis, treatment, and management of AHD and OIs.
HIV New Product Introduction Toolkit: This website provides a framework and resources to support the introduction of new HIV and AHD products in national health systems