Mrs. M.R, a 65-year-old South Indian woman, visiting family in Australia, was admitted in January 2015 for the management of new congestive cardiac failure (CCF).
She had been recently discharged from a different hospital with symptoms consistent with community-acquired pneumonia and managed with intravenous ceftriaxone and azithromycin followed by amoxicillin/clavulanate and roxithromycin. Investigations at this time included a chest X-ray demonstrating right lung lower zone consolidation, and blood and sputum cultures were negative for routine pathogens; sputum acid-fast bacilli (AFB) smears were negative. She subsequently developed worsening bilateral peripheral limb oedema, increasing exertional dyspnoea and paroxysmal nocturnal dyspnoea, and was admitted to our hospital for further management. Clinical examination was consistent with congestive cardiac failure with evidence of atrial fibrillation. Additionally the patient was found to have cervical and parotid lymphadenopathy measuring approximately 1–2 cm in size.
Her past medical history included ischaemic heart disease, atrial fibrillation, hypertension, osteoarthritis, asthma, herpes zoster (6 months prior to admission), laparotomy in 1968 for an unclear indication, and total hysterectomy in 1991. Further history revealed a 6-month history of 5 kg weight loss with no anorexia, and she denied fevers and night sweats. There was no other travel history besides to Australia. She had been married since the age of 19 and denied other sexual partners. There was no history of tattoos or injecting drug use. She had no animal contact or gardening activities.
Initial laboratory investigations revealed pancytopenia with a normocytic anaemia: haemoglobin 80 g/L (115–165 g/L), mean cell volume 84 fL (80–96 fL), white cell count 3.0 × 109/L (4–11 × 109/L), with normal neutrophils 2.5 × 109/L (2–7.5 × 109/L) and lymphopenia 0.2 × 109/L (1–4 × 109/L), and platelets 55 × 109/L (150–400 × 109/L). Her chest X-ray was consistent with fluid overload with bilateral pleural effusions and there was evidence of right lung lower zone consolidation.
Given the pancytopenia, lymphadenopathy and weight loss, Mrs. M.R proceeded to have computerised tomography (CT) of the neck, chest, abdomen and pelvis. This revealed widespread mediastinal, hilar and peritoneal lymphadenopathy as well as multiple peripherally enhancing cystic lesions within the right parotid gland, raising the possibility of tuberculous adenitis. A positron emission tomography scan demonstrated metabolically active retroperitoneal, mesenteric and inguinal lymph nodes. Transthoracic echocardiography revealed normal left ventricular size and function, impaired right ventricular systolic function as well as diastolic dysfunction, and severe pulmonary hypertension (pulmonary artery systolic pressure 57 mmHg + right atrial pressure). CT pulmonary angiogram did not reveal evidence of pulmonary embolus, and screening tests for connective tissue disorders as a cause for secondary pulmonary hypertension were unremarkable. In view of her country of origin and respiratory symptoms, sputum AFB smears were repeated and were negative. Quantiferon-Gold testing was indeterminate.
Given her unexplained lymphadenopathy and weight loss, Mrs. M.R went on to have human immunodeficiency virus testing. The HIV-1/2 enzyme immunosorbent assay (EIA) (Roche) at our hospital was unexpectedly strongly positive on two occasions and the sample was sent to the Victorian Infectious Diseases Reference Laboratory for confirmation. The HIV-1/2 EIA using different platforms (Genscreen and Liaison XL) was also positive but the HIV-1 p24 antigen was negative. The HIV-1 western blot was negative. This prompted testing for HIV-2, performed at the National Reference Laboratory, using an in-house HIV-2 western blot (Fig. 1) and the BioRad Multispot EIA assay, which is able to differentiate between HIV-1 and HIV-2 antibodies. Both tests confirmed HIV-2 infection. HIV-2 viral load (VL) was performed using a research-based assay and was detected at 3260 copies/mL. Resistance testing demonstrated susceptibility to all protease inhibitors and nucleoside reverse transcriptase inhibitors; resistance to non-nucleoside reverse transcriptase inhibitors was consistent with HIV-2. Her CD4 T cell count was 118 cells/µL (17%) (650–2000 cells/µL; 35–59%). Further questioning revealed the patient received a blood transfusion in 1991 during her hysterectomy in India; no other risk factors for HIV infection were determined, and her husband tested negative for HIV-1 and HIV-2.
Given this new diagnosis of HIV-2 infection, a number of potential differential diagnoses were considered for Mrs. M.R’s pancytopenia, widespread lymphadenopathy, weight loss and ongoing respiratory issues. Multiple lymph node aspirates and core biopsies, bone marrow aspirate and trephine, and bronchoscopy were performed and did not reveal a microbiological or haematological diagnosis; investigations for mycobacterial, fungal and opportunistic infections were negative on all specimens.
She was commenced on anti-retroviral therapy with fixed-dose combination emtricitabine 200 mg + tenofovir 300 mg daily and ritonavir (200 mg)-boosted lopinavir 800 mg daily, a regimen widely available in India. She was also commenced on trimethoprim-sulfamethoxazole for Pneumocystis jiroveci prophylaxis. Within 2 months her VL was undetectable and her CD4 cell count was improving, after an initial decline. Her pancytopenia improved and her lymphadenopathy regressed over the next 2 months and these were subsequently attributed to HIV-2 infection.
Mrs. M.R continued on anti-retroviral treatment and remained well until she returned to India.
