Complications And Adverse Drug Reaction Occurrence in Human Immunodeficiency Virus and Extra-Pulmonary Tuberculosis Co-Infected Individuals: An Educational Case Report

Abstract

Human immunodeficiency virus (HIV) positive individuals are highly susceptible to extrapulmonary tuberculosis (EPTB) and other opportunistic infections due to immune suppression. The co-administration of antiretroviral therapy (ART) and anti-tuberculosis therapy (ATT) often causes overlapping adverse effects, creating significant treatment challenges. This case report illustrates the clinical complexity in managing a patient with HIV and EPTB who developed oral candida infection, acute gastritis, and anemia shortly after starting ATT. Supportive care, including antifungal therapy, symptomatic treatment, and iron supplementation, was crucial in addressing these complications while continuing ART and ATT. The case highlights the importance of close monitoring and prompt intervention to prevent treatment interruptions and achieve favorable clinical outcomes in HIV and tuberculosis (TB) co-infected patients.

Keywords

Introduction

According to the World Health Organisation, EPTB refers to tuberculosis affecting sites outside the lungs, which is 30 times more frequent and severe in patients experiencing dual burden with HIV [1,3]. As Cluster of differentiation 4 (CD4) cell counts decline, the likelihood of EPTB increases, often presenting as lymphadenitis, disseminated tuberculosis, or other severe forms associated with advanced immunosuppression [2]. This immune compromise alters the typical presentation of TB, leading to atypical and often more complex manifestations like lymph node TB which is significantly prevalent [3][4]. The concurrent use of ART and first-line ATT may heighten the incidence, intensity, and complexity of adverse drug reactions.  Research suggests that up to 25.8% of patients co-infected with HIV and TB may experience significant adverse events during ATT, particularly within the initial week of treatment [5]. Due to their immunosuppressed state, HIV-positive patients are also at high risk for opportunistic infections. Oral candida, for instance, is reported in approximately 80–90% of individuals with HIV [6]. Anaemia is also a reported complication, with its 16-47% among those on ART [7].  This case report details the clinical course of a 29-year-old male with HIV on stable ART who developed cervical lymphadenopathy attributed to EPTB. Following the initiation of ATT, he presented with gastrointestinal disturbances, oral candida, and marked anaemia. This case underscores the complexity of managing overlapping toxicities between ART and ATT, the challenges of immune reconstitution, and the heightened vulnerability to opportunistic infections.

Case Presentation:

A 29-year-old male is presented to the emergency department with the chief complaints of severe neck pain for 1 week, loose stools (six episodes), and vomiting (five episodes). The patient also complains of severe stomach pain. The patient revealed past medical history with acquired immunodeficiency syndrome (AIDS) for the past eight months. He was under the medication of tenofovir disoproxil fumarate 300mg along with lamivudine 300mg and dolutegravir 50mg in tablet form (TLD regimen) once daily. He ensured adherence to the medication for the last eight months. No side effects are mentioned.  The patient had a personal history of alcohol consumption for six years. The patient also claimed cessation of alcohol 2 months ago. One week before admission, the patient developed fever, hypotension, and painful swelling on the left side of his neck. The patient was diagnosed with cervical lymphadenopathy based on the fine needle aspiration cytology (FNAC) results at an outside facility. The patient was further prescribed d a tablet form of rifampicin 150mg + isoniazid 75mg + pyrazinamide 400mg + ethambutol 275mg once daily. The patient also consumes tablet form of pyridoxine 50mg and dolutegravir 50mg. On physical examination, mouth ulcers were noted. Upper endoscopic results mentioned no abnormal findings in the oesophagus and stomach. Culture test results supported the growth of Candida albicans. Peripheral smear report confirmed moderate degree microcytic hypochromic anaemia. Recent gastric symptoms led to suspicion of ATT-induced acute gastroenteritis. Laboratory evaluation revealed anaemia (haemoglobin 7.5g/dl), leukocytosis (white blood cell count 14,300/mm³), and moderate immunosuppression (CD4 count 498 cells/mm³). The final clinical diagnosis included HIV on ART, EPTB on ATT, oral candida, acute gastritis, and anaemia.

Treatment given:

• Intravenous (IV) administration of emeset (8mg three times daily)
• Empiric antibiotic coverage with ceftriaxone (1g IV twice daily) and azithromycin (500mg orally once daily) was provided.
• pantoprazole IV 40mg twice daily.
• Tab. Fluconazole (100mg orally once daily)
• Tab. Chlorpheniramine maleate (4mg at bedtime) and oral rehydration solution addressed other symptoms.

On day 2, intravenous iron sucrose (200mg in 100ml normal saline) was started, administered as five doses on alternate days (days 2, 4, 6, 8, and 10). By day 4, tablet form of cotrimoxazole (trimethoprim 80mg+ Sulphamethoxazole 400mg) twice daily was introduced for prophylaxis of opportunistic infections, along with supplementation of pyridoxine (40mg daily), Capsule. vitamin C (three times daily), and intravenous asthymine forte (100ml over two hours) continued through day 11. Ceftriaxone and Tab. fluconazole were discontinued on day 8, while the remaining therapy was maintained until day 11. By day 5 of hospitalisation, the symptoms of burning mouth and gastritis had markedly subsided. By day 10, the patient’s haemoglobin level had increased to 10.5 g/dL. Overall, the patient exhibited significant clinical improvement during hospitalisation and was discharged on day 11.

DISCUSSION:

Most individual studies suggest that HIV infection increases the risk of EPTB compared to pulmonary tuberculosis (PTB) [1]. Unlike other opportunistic infections such as cryptococcal meningitis or toxoplasmosis—which usually occur at very low CD4 counts (<300 cells/µL)—TB is unique in that it can manifest across a wide range of CD4 counts. In the present study, 78% of patients were initiated on ART. Treatment success rates among coinfected patients not receiving ART were significantly lower compared to those already on ART [4]. The higher prevalence of EPTB among HIV-positive individuals may be attributed to immune suppression, which predisposes patients to disseminated TB. Serious adverse drug events (SADEs) occurred exclusively in patients with TB–HIV coinfection, with none reported in the TB-only group. Previous studies have identified vomiting, diarrhoea, and anaemia as common adverse drug events (ADEs) among coinfected patients. The long duration of therapy, polypharmacy, and altered pharmacokinetics and pharmacodynamics in HIV-positive individuals are recognised as contributing factors. Notably, most ADEs occur during the first week of therapy, as reported in a Chinese study where 54.7% of patients on directly observed therapy (DOT) for first-line anti-TB drugs experienced adverse drug reactions (ADRs) [5]. Opportunistic fungal infections such as oral thrush (oropharyngeal candida infection) are also common in HIV patients due to impaired immunity. Candida species normally reside in the oral cavity without causing symptoms, but in immunocompromised hosts, the infection can progress rapidly. The standard treatment is oral fluconazole 100 mg once daily, except during pregnancy. Anaemia in HIV–TB coinfected patients can result from the combined impact of HIV infection, ART and anti-TB medications, inflammatory mediators, and opportunistic infections [7]. Management includes intravenous iron sucrose 200 mg for anaemia, injection emeset 8 mg for vomiting, and injection pantoprazole 40 mg intravenously for gastritis [11]. For lymph node TB, the recommended regimen is the standard six-month first-line ATT [8]. In terms of ART, dolutegravir (DTG) remains the preferred option in first- and second-line therapy due to its safety profile [9]. Current guidelines recommend dolutegravir 50 mg twice daily only when rifampicin is included in the regimen [10]. Overall, HIV coinfection not only increases the risk of EPTB but also exacerbates TB progression, raises the likelihood of ADEs, and necessitates careful management of comorbid opportunistic infections and hematological complications. The strength of this case lies in its detailed clinical documentation, including microbiological confirmation of oral candida infection and peripheral smear findings for anaemia, which enhances diagnostic accuracy. It highlights the real-world complexity of managing HIV/TB co-infection complicated by opportunistic infections and drug-induced adverse events, providing educational value for clinicians facing similar scenarios. The case also demonstrates effective strategies to maintain both ART and ATT without interruption, thereby emphasising treatment continuity. However, as a single-patient report, its findings are not generalizable, and the absence of long-term follow-up limits understanding of sustained outcomes. Additionally, while anemia was confirmed, comprehensive investigations such as iron studies, vitamin B12, and folate levels were not performed to fully elucidate its aetiology, which restricts the depth of causal analysis.

CONCLUSION:

This case highlights how difficult it can be to manage adverse medication reactions when polypharmacy is present, especially in patients who are co-infected with HIV and EPTB.  Although finding the exact cause is frequently challenging, prompt identification and treatment are crucial to reduce morbidity.  To lessen the burden of therapy and improve quality of life, this study emphasises the necessity of close observation, interdisciplinary teamwork, and patient-centred approaches by presenting a real-world situation in which problems and medication reactions coexisted.

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