Incidence and Determinants of Active Tuberculosis in HIV-Positive Patients on Second-Line ART in Addis Ababa, Ethiopia: A Five-Year Retrospective Study

In many parts of the world, two powerful diseases often travel together, making life harder for those who carry them. One is HIV, a virus that slowly weakens the body's natural defense system, leaving it vulnerable to other infections. The other is tuberculosis, a bacterial disease that primarily attacks the lungs but can spread to other parts of the body. When a person has HIV, their immune system struggles to fight off tuberculosis, and when they have tuberculosis, it can make HIV progress faster. For decades, doctors have used a combination of medicines called antiretroviral therapy to keep HIV under control. These drugs are so effective that they have saved millions of lives. However, for some patients, the first set of medicines stops working, forcing doctors to switch them to a second, more complex set of drugs. While these second-line treatments are powerful, it remains unclear how well they protect patients from catching tuberculosis, especially in places where the disease is common. Understanding this risk is vital because if doctors know exactly who is most likely to get sick, they can focus their care and resources to keep those people safe.

A team of researchers at Yekatit 12 Hospital Medical College in Addis Ababa, Ethiopia, decided to investigate this specific question. They looked back at the medical records of 350 adults who had been switched to second-line antiretroviral therapy. These patients had already tried the first set of medicines, which had failed to control their HIV, so they were moved to the stronger regimen. The researchers followed these patients over a five-year period, from the beginning of 2021 to the end of 2025. Their goal was simple: to count how many of these patients developed active tuberculosis during that time and to figure out what factors made some more likely to get sick than others. They examined everything from the patients' age and education to their weight, how well they took their medicine, and the state of their immune system.

The study revealed that tuberculosis is still a persistent threat, even for patients on these advanced treatments. Out of the 350 people followed, 17 developed active tuberculosis. This might sound like a small number, but it translates to a steady rate of new cases appearing over time. The researchers calculated that for every 100 people on this treatment for a full year, roughly one would develop tuberculosis. While this rate is lower than what was seen in earlier eras of HIV care, it is not zero. The fact that people are still getting sick suggests that the second-line medicines alone are not enough to completely block the disease for everyone.

When the researchers dug deeper into the data, they found that the risk was not spread evenly across the group. Three main factors stood out as strong predictors of who would get tuberculosis. The first was the overall health of the patient's immune system at the time they started the second-line treatment. Patients who were already in an advanced stage of HIV disease, where their immune systems were severely damaged, faced a much higher risk. In fact, those in the most advanced stages were nearly nine times more likely to develop tuberculosis than those who were in earlier stages. This suggests that the damage done to the body before switching to the new drugs is hard to reverse, leaving a lasting vulnerability.

The second major factor was how consistently patients took their medication. The study found a clear pattern: the less strictly a patient followed their dosing schedule, the higher their risk of getting tuberculosis. Patients who missed a few doses were significantly more likely to get sick, and those who missed many doses faced the highest risk of all. This relationship was so strong that it acted like a warning light; poor adherence to the second-line regimen directly correlated with a higher chance of developing the infection. The third factor was physical nutrition. Patients who were underweight, with a body mass index below a healthy threshold, were also at a significantly higher risk. Being undernourished appeared to weaken the body's ability to fight off the bacteria, even when the HIV virus itself was being controlled by the drugs.

Interestingly, the study found that some other factors people might expect to be important were not the main drivers in this group. For instance, having a history of tuberculosis before starting the second-line treatment did not independently predict who would get sick again. Similarly, the specific type of second-line drug regimen used did not make a significant difference in the risk of developing tuberculosis. The most critical elements were the patient's current immune status, their commitment to taking their pills, and their nutritional health.

The researchers also noted that when these 17 patients did develop tuberculosis, most of them were diagnosed with the lung form of the disease, which is the most common type. Despite the seriousness of the situation, the outcome for these patients was positive. All 17 individuals who were diagnosed received treatment and improved, with no deaths recorded among them during the study period. This suggests that when the disease is caught and treated, the medical system in place is effective at saving lives. However, the researchers emphasized that the goal should be to prevent the illness from happening in the first place.

The findings from this study offer a clear path forward for doctors and health programs. They show that simply switching a patient to stronger HIV medicines is not a complete solution. To truly protect these vulnerable patients, healthcare providers need to pay close attention to three areas. First, they must identify patients who are in advanced stages of HIV and provide them with extra support. Second, they need to help patients stick to their medication schedules, perhaps through community support or better counseling, because missing doses opens the door to infection. Finally, they must address nutrition, ensuring that underweight patients receive the dietary support they need to strengthen their bodies. By focusing on these specific, actionable areas, health programs can reduce the burden of tuberculosis and keep more people living with HIV healthy and safe.