Fever of Unknown Origin (FUO) in HIV Infection in the Era of Antiretroviral Treatment (ART) in India: Development of a Simple Diagnostic Algorithm

Objective: Fever of unknown origin (FUO) is a challenging problem among people living with HIV (PLHIV).With increasing access to Anti-retroviral treatment (ART), the spectrum of causes of FUO has evolved in the developed world. This study evaluated the etiology of FUO among PLHIV in the era of ART in India.
Methodology: This prospective study was conducted at a tertiary-care institution in New Delhi, India. Sixty four PLHIV with a diagnosis of FUO were assessed by detailed clinical evaluation and immunological assessment. Specific investigations to identify the etiology of fever: microbiological and radiological investigations, bone marrow and histopathological examination of biopsies were performed. A simple diagnostic algorithm for FUO was developed based on the findings.
Results: Sixty five episodes of FUO were studied. Seventy percent of subjects were men, 76% were <40 years of age, and 39% were receiving ART. The mean CD4 count was 156.57±178.43 cells/mm3 (5 to 1144 cells /mm3) and 23% patients had CD4 counts <50 cells/mm3. The mean duration of fever was 11.26±8.54 weeks. Infections were the most common cause for FUO, with Tuberculosis the most common (61.54%), particularly disseminated tuberculosis (41.54%). Cryptococcal meningitis (7.69%), bacterial pneumonia (4.62%), pyogenic abscesses (4.62%), Pneumocystis jirovecii pneumonia (PCP) (3.08%), visceral leishmaniasis (3.08%) were other infections observed. Non-infectious etiologies including lymphoma (4.62%) and progressive multifocal leucoencephalopathy (PMLE) (3.08%) were also seen. The etiology remained undiagnosed in 6.15% episodes. Importantly, two or more concurrent etiologies of fever were seen in 60% of patients.
Conclusion: Infections especially Tuberculosis remain the most common cause of FUO in PLHIV even in the era of ART in developing countries like India. Multiple concurrent infections and a rising trend to non-infectious causes are being observed. A simple diagnostic algorithm will help diagnose majority of FUO even at the peripheral centers.