A 9-month-old female presented to Hospital Central de Maputo with 3 days of cough which progressed to respiratory distress, poor oral intake, fever, lethargy, and white oral plaques. She was hypoxic with oxygen saturations of 85% on room air with tachypnea and subcostal retractions. Her admission laboratory included a full blood count with leukocytes of 18.7 x 103 cells/uL, hemoglobin of 7.3 g/dL, and platelets of 73 x 103/uL, and a biochemistry panel with normal creatinine, transaminases, and basic electrolytes. She was diagnosed with severe pneumonia, oral candidiasis, moderate anemia, and severe acute malnutrition (weight for height Z score = 0.1 percentile), admitted, and started on oxygen supplementation, intravenous antibiotics and antifungal therapy, and therapeutic milk.
The mother was HIV-positive and had been on antiretroviral treatment (ART) for 7 years, but due to nausea and vomiting during the first trimester of pregnancy she stopped taking her regimen of tenofovir/lamivudine/dolutegravir and did not resume treatment after birth. She reported an uncomplicated pregnancy and vaginal delivery at 41 weeks of gestation, with APGAR scores of 8 and 9 at 1 and 5 min, respectively. The infant received post-natal prophylaxis with 6 weeks of zidovudine and 12 weeks of nevirapine treatment for prevention of mother to child transmission of HIV (PMTCT). She had a negative DNA polymerase chain reaction (PCR) test at 1 month of age and was initiated on cotrimoxazole prophylaxis. She was breastfeeding and in HIV-exposed infant follow-up care until the age of 6 months, after which time she was lost to follow-up. There were no prior hospitalizations and no known tuberculosis (TB) contacts.
Given the history and clinical presentation at admission, a point-of-care HIV nucleic acid test was ordered and returned positive. With this finding, and a chest radiograph that had bilateral interstitial opacities, treatment for Pneumocystis jirovecii and cytomegalovirus were added. Her baseline HIV RNA PCR viral load was >1,000,000 copies/mL, and she had severe immune suppression with a CD4 cell count of 280 cell/mm3 and 23%. COVID-19 PCR was negative as were TB diagnostic tests including Xpert MTB/Rif  (on nasopharyngeal aspirate and stool specimens) and urine lipoarabinomannan (LAM).
On developmental history, the mother reported that she was initially meeting most age-specific developmental milestones until 6 months of age. She tracked objects across visual field at 2 months, had full head control at 3 months, sat with assistance at 5 months, and sat independently at 6 months. After 6 months of age, the patient started to regress with loss of development milestones, and prior to admission she could no longer sit independently and lost head control. The mother also reported progressive weakness, apathy, and decreased interactivity, but denied any focal neurologic deficits or history of seizures.
On her intake neurologic examination, she was responsive but lethargic. There was significant bilateral upper extremity hypertonicity, bilateral hyperreflexia of the biceps tendons, and mild axial hypotonia. Lower extremity tone and reflexes were normal. She had right eye divergent strabismus, but no other notable cranial nerve abnormalities. The anterior fontanelle was normotensive, and there was no nuchal rigidity. Head circumference was at the 8th percentile for age (42 cm), with a decrease in growth velocity based on previous measurements documented on the infant's health card. The remainder of the neurologic examination was within normal limits without any asymmetry noted. There was no history of seizures.
Supplementary examinations including neuroimaging (computerized tomography or magnetic resonance imaging) and toxoplasmosis and cytomegalovirus serologies were not available. However, based on the developmental regression and abnormal neurologic examination with pathological upper extremity reflexes and hypertonia, a clinical diagnosis of HIVE was made. She was discharged after 11 days of hospitalization with resolution of her respiratory illness and improvement in her nutritional status, but without any changes in her neurologic examination. ART was initiated on the day prior to discharge with a regimen of abacavir, lamivudine, and lopinavir/ritonavir (LPV/r).
After discharge, she was referred for physical and occupational therapy, outpatient nutritional rehabilitation, and maintained monthly outpatient follow-up for her HIV, with good reported ART adherence. She had one readmission at 11 months of age for acute gastroenteritis with dehydration for 7 days. After 12 months of age and 3 months on ART, her viral load had decreased to 729 copies/mL, her weight had increased from 5.1 to 7.0 kg, with normal acute nutritional status classified by weight for length Z score, and her head circumference for age was now in the 12th percentile. Developmentally, she had improved head control, was sitting independently in tripod position, displayed more social interaction, and showed age-appropriate separation anxiety. She was able to roll-over, was babbling, and had raking grasp, but was still not crawling, standing, or walking with support. On neurologic examination, she had improved axial hypotonia, with resolution of upper extremity hypertonia. Strabismus was unchanged.
At 15 months of age and 6 months on ART, she continued to gain weight and show neurodevelopmental improvement. She was now able to sit independently, stand and take a few steps with support, transfer objects between hands, and had two words that she routinely used. On examination, her axial muscular tone, appendicular muscular tone and reflexes were symmetric and intact, and her strabismus was less pronounced.