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Mortality rate and determinants of death in HIV-associated extrapulmonary tuberculosis: A ten-year retrospective cohort study

This ten-year retrospective cohort study in Abidjan, Côte d'Ivoire, reveals that extrapulmonary tuberculosis is highly lethal among HIV-infected adults, with mortality rates reaching 58% for tuberculous meningitis and peaking within the first two months of treatment, while identifying cotrimoxazole prophylaxis and higher CD4 counts as significant protective factors.

Original authors: Frederic Nogbou Ello, Affoue Gisele Kouakou, Doumbia Adama, Alain N’douba Kassi, Chrysostome Mossou, Anatole Mian, Aristophane Tanon, Fabrice Bonnet, Serge Paul Eholie

Published 2026-06-29

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Original authors: Frederic Nogbou Ello, Affoue Gisele Kouakou, Doumbia Adama, Alain N’douba Kassi, Chrysostome Mossou, Anatole Mian, Aristophane Tanon, Fabrice Bonnet, Serge Paul Eholie

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

The Big Picture: A Hidden Danger in the Body

Imagine the human body as a large, bustling city. Usually, when a bad invader (the tuberculosis bacteria) attacks, it sets up camp in the "lungs district." This is the most common type of TB.

However, in people living with HIV, the city's security force (the immune system) is weakened. This allows the invader to escape the lungs and spread to other parts of the city—like the brain, the lining of the heart, or the lymph nodes. This is called Extrapulmonary Tuberculosis (EPTB).

This study, conducted over ten years in Abidjan, Côte d'Ivoire, looked at a massive group of 2,046 people who had both HIV and TB. The researchers wanted to answer two main questions:

Where does this "invader" like to hide when it leaves the lungs?
What makes it more likely for a patient to survive or not?

The Findings: Where the Invader Hides

Out of the 2,046 patients, more than 60% had the infection spread outside their lungs. It wasn't just a few cases; it was the majority.

The researchers found the "invader" was most likely to set up shop in three specific neighborhoods:

The Lymph Nodes (32%): Think of these as the city's security checkpoints. The bacteria loved to clog them up.
Miliary TB (23.6%): This is like a "shower" of bacteria spreading everywhere at once, affecting many organs simultaneously.
Tuberculous Meningitis (TBM) (16.4%): This is the most dangerous neighborhood. The bacteria attacks the brain and spinal cord coverings.

The Danger Zone: The First Two Months

The study revealed a terrifying timeline. If a patient was going to die, it usually happened very quickly.

The "Critical Period": The first 60 days of treatment were the most dangerous. It's like the first two weeks after a major surgery where the risk of complications is highest.
The Death Rate: Overall, 38% of the patients with this type of TB died.
- For those with the brain infection (TBM), the death rate was a staggering 58%.
- For those with the "shower" type (Miliary), it was 43%.
- For those with infections in the fluid sacs around organs (serous membranes), it was 49%.

The "Life Rafts": What Helped People Survive?

The researchers looked for factors that acted like life rafts, keeping patients afloat during that dangerous first two months. Two things stood out as powerful protectors:

The "Shield" (Cotrimoxazole): This is a common antibiotic. Patients who took this pill as a preventative measure had a much better chance of survival. It acted like a secondary shield, stopping other infections from attacking while the body fought the TB.
The "Security Force" (CD4 Count): In the world of HIV, the CD4 count measures how many security guards (immune cells) are left.
- Patients with a low count (fewer than 100 guards) were in deep trouble.
- Patients with a higher count (100 or more) had a four times better chance of surviving. It's the difference between a city with a few guards and a city with a full army.

The "Risk Factors": What Made Things Worse?

Certain factors were like heavy anchors, dragging patients down:

The Location: Having the infection in the brain (TBM), the fluid sacs, or spread everywhere (Miliary) was the biggest predictor of death.
Retreatment: Patients who had been treated for TB before and failed (relapse) were at higher risk. It's like trying to fix a house that has already collapsed once; the foundation is weaker.
Low Immunity: As mentioned, having very few immune cells was a major risk.

The Conclusion: What This Means

The study concludes that for people with HIV in this region, TB outside the lungs is a frequent and deadly threat. The first two months of treatment are a "make or break" period.

The key takeaways are simple but vital:

Diagnose early: Find the HIV and the TB before the immune system is completely destroyed.
Start treatment fast: Get the patient on HIV medication (ART) and TB medication immediately.
Use the shield: Make sure patients are taking their preventative antibiotics (Cotrimoxazole).
Watch the brain: Be extra careful with patients who have symptoms in the brain or fluid around organs, as they need the most urgent care.

In short, this study sounds the alarm that when TB escapes the lungs in HIV patients, it becomes a race against time. But with the right tools (early diagnosis, strong immunity, and preventative meds), many more lives can be saved.

Technical Summary: Mortality Rate and Determinants of Death in HIV-Associated Extrapulmonary Tuberculosis

Problem Statement
Extrapulmonary tuberculosis (EPTB) is a leading cause of mortality among people living with HIV (PLHIV) in sub-Saharan Africa. Despite the high burden of disease, site-specific mortality patterns and risk factors for EPTB remain poorly characterized, particularly in resource-limited settings. While tuberculous meningitis (TBM) is recognized as highly fatal, the diversity of anatomical sites involved in EPTB necessitates a more granular understanding of mortality risks across different forms of the disease. In Côte d'Ivoire, where TB/HIV co-infection is prevalent, there is a need to evaluate the outcomes of HIV-infected adults with EPTB to inform diagnostic and therapeutic strategies.

Methodology
This study employed a retrospective cohort design conducted at the Service des Maladies Infectieuses et Tropicales (SMIT) of Treichville University Hospital in Abidjan, Côte d'Ivoire. The study population comprised 2,046 HIV-infected adults (≥18 years) with TB/HIV co-infection registered between January 1, 2010, and March 31, 2019.

Data Collection: Data were extracted from medical records using a standardized form, capturing sociodemographics, laboratory results (CD4 count, HIV type, bacterial load), treatment status (ART, cotrimoxazole prophylaxis), and TB classification.
Definitions: EPTB was defined as Mycobacterium tuberculosis infection affecting organs outside the pulmonary parenchyma, diagnosed via culture, histology, or strong clinical evidence. Patients were categorized by anatomical site (e.g., lymph nodes, miliary, TBM, serous membranes).
Statistical Analysis: Survival was estimated using Kaplan–Meier methods, with the log-rank test used to compare distributions. Risk factors for death were identified using a stratified Cox proportional hazards model. Variables with $p < 0.25$ in univariate analysis were included in the multivariable model, with adjustments for age and lymphocyte count. The assumption of proportional hazards was tested, and violations were addressed via stratification.

Key Results
Among the 2,046 co-infected patients, 1,240 (60.6%) presented with EPTB. The most frequent localizations were lymph nodes (32.0%), miliary tuberculosis (23.6%), and tuberculous meningitis (TBM, 16.4%).

Mortality Rates: The overall mortality rate for EPTB was 38% (470/1,240). Mortality varied significantly by site:
- TBM: 58%
- Serous membrane TB (pleural, peritoneal, pericardial): 49%
- Miliary TB: 43%
- Genitourinary TB: 21%
- Lymph node TB: 31%
Timing of Death: The majority of deaths occurred within the first 60 days of anti-tuberculosis treatment (ATT) initiation, indicating a critical early period of vulnerability.
Risk Factors (Multivariable Analysis):
- Independent Risk Factors for Death: TBM (adjusted Hazard Ratio [aHR] 2.20; 95% CI 1.28–3.74) and serous membrane TB (aHR 1.77; 95% CI 1.02–3.09). Miliary TB showed a trend toward increased mortality (aHR 1.66; 95% CI 0.98–2.82).
- Protective Factors: Cotrimoxazole prophylaxis (aHR 0.65; 95% CI 0.53–0.80) and a CD4 count $\ge$ 100 cells/mm³ (aHR 0.26; 95% CI 0.18–0.36).
Survival Trajectory: Survival probability declined sharply during the first two months of treatment, particularly for TBM and miliary TB, before stabilizing after three months. Patients with CD4 counts $\ge$ 200 cells/mm³ had a 90% survival probability compared to 34% for those with CD4 < 100 cells/mm³.

Key Contributions and Significance
The paper contributes to the literature by providing a detailed, site-specific breakdown of mortality in HIV-associated EPTB within a large cohort in West Africa. Its primary contributions include:

Characterization of Mortality Patterns: The study highlights that EPTB is not a monolithic entity; mortality risks are heavily concentrated in specific disseminated forms (TBM, serous membrane, and miliary TB), which account for the majority of deaths.
Identification of the "Critical Period": The data underscores that the first two months of treatment are the most perilous, suggesting that current diagnostic and therapeutic interventions may be insufficient during this early window.
Validation of Protective Interventions: The study confirms the strong protective effect of cotrimoxazole prophylaxis and immune reconstitution (CD4 $\ge$ 100 cells/mm³) against mortality in EPTB patients, independent of other factors.

Claims and Limitations
The authors claim that their findings support the urgent need for earlier HIV diagnosis, prompt initiation of antiretroviral therapy (ART), and strengthened diagnostic algorithms for disseminated EPTB in resource-limited settings. They emphasize that cotrimoxazole prophylaxis is a critical, modifiable factor for survival.

The paper modestly acknowledges limitations inherent to its design:

Generalizability: As a single-center study at a tertiary referral hospital, the results may reflect a population with more severe disease and complex cases than the general TB/HIV population in Côte d'Ivoire.
Diagnostic Uncertainty: Some EPTB cases were presumptively diagnosed due to the difficulty of obtaining specimens, potentially leading to misclassification.
Data Gaps: The retrospective nature precluded the collection of certain data points, such as serial CD4 counts, HIV viral load, and specific causes of death, which limits the ability to fully adjust for all confounding variables.

Despite these limitations, the authors assert that the study provides critical evidence to inform policy at district and national levels regarding the management of HIV-associated EPTB.