The following cases illustrate the complexities involved in recognizing and correctly diagnosing primary HIV infection (PHI). Extensive lab work, but also thorough history taking, is required. Patient 1 was not recognized as suffering from PHI until after she was discharged from the hospital. Patient 2 was recognized with PHI, and his symptoms spontaneously resolved. Patient 3 required extensive hospitalization because of pulmonary complications. Viral loads declined sharply without medication for both patients 1 and 2, upon resolution of symptoms. However, patient 3 maintained a high viral load and was started on triple-drug antiretroviral therapy. None of the patients were started on antiretroviral therapy during the acute retroviral syndrome phase of PHI, which is currently recommended in US treatment guidelines.
A 43-year-old woman presented to the emergency room with confusion, stiff neck, fever, headache, and sore throat that had lasted for over 2 weeks. According to the family, a physician who saw the patient 2 weeks prior to hospital admission prescribed her first cephalexin and later amoxicillin/clavulanic acid. At the emergency room, she had a temperature of 38°C, tender submandibular lymphadenopathy, disorientation, and drowsiness, with intact strength and reflexes. She had no prior relevant medical or surgical history, no medications, and no "sick contacts." A lumbar puncture showed total protein 209 mg/dL, glucose 42 mg/dL, and white blood cells 48 cells/mm3 (99% lymphocytes). A CT of the head showed no acute changes and the chest x-ray was clear. Initially, she was empirically treated with ceftriaxone and acyclovir for presumptive diagnosis of bacterial meningitis and herpes simplex encephalitis. She markedly improved by day 5 when acyclovir was stopped.
She was discharged on day 9 with diagnosis of possible "partially treated bacterial meningitis." Since one health care provider sustained a needle stick while the patient was at the emergency room, a patient blood sample was examined for HIV by ELISA. The HIV serology was positive. CD4 cell counts and viral load were not obtained. The patient was seen at a clinic 3 months after being discharged from the hospital. At that time, the HIV ELISA and Western Blot were positive. The CD4 cell count was 466 cells/mm3 (35.3%) and the viral load 9749 copies/mL. A more thorough history revealed that she was engaged in a heterosexual relationship with a new partner "who was sick" 3 months prior to the onset of her symptoms.
A 31-year-old bisexual man presented to the emergency department complaining of progressive headaches, confusion, myalgia, vivid nightmares, and diarrhea. For many years he had traveled extensively throughout sub-Saharan Africa and had recently spent 2 years in Madagascar. He had returned to the United States 1 month before admission. Once home, he developed diffuse myalgia and malaise. Stool analysis showed hookworm and Entamoeba histolytica, and he was treated with mebendazole and metronidazole 1 week before admission. During that week, he developed flu-like symptoms of fever, chills, cough, and persistent diarrhea. Three days before admission, he developed a stiff neck, headaches, confusion, and vivid nightmares.
Within the past 6 months, he had been sexually active with 4 partners, all in Africa. He reported 1 episode of gonococcal urethritis within the past 2 months. He did not use condoms consistently. His last HIV serologic test, 3 months earlier, had been negative. On physical examination, the patient had a temperature of 38°C, blood pressure, 105/76 mm Hg; pulse rate, 75 beats per minute; and respirations, 16 breaths per minute. His neck was supple, without lymphadenopathy. Funduscopic examination was normal, but he had a visual field defect in the left eye. The only other notable finding was a faint maculopapular rash over his trunk and extremities. His complete blood count (CBC) results were normal. CD4 T-cell count was 410 cells/mm3 and CD8 T-cell count was 940 cells/mm3. Serologic tests for syphilis, Epstein-Barr virus, and HIV antibody were negative except for a p24 antigen level of 5100 pg/mL. His HIV RNA level was 3.6 million copies/mL.
On the fifth hospital day, the patient's fever, rash, headaches, visual field defect, and other symptoms resolved spontaneously without treatment. All cultures remained negative. He was discharged to the HIV outpatient clinic for follow-up and eventual treatment. His plasma p24 antigen became undetectable. His HIV RNA levels declined to 3000 copies/mL, and his CD4 T-cell count rose to 650 cells/mm3. Repeat HIV serologic testing showed a positive HIV enzyme immunoassay and a positive Western blot with bands at gp120, gp160, and p24. One year later the patient remained asymptomatic.
A 23-year-old woman was admitted to the hospital for evaluation of pneumonia. Three weeks earlier, she had suddenly developed a sore throat, sinus congestion, and temperatures to 40°C. She was treated empirically for sinusitis with clarithromycin and amoxicillin. Over the next 2 weeks, she developed persistent fevers as well as nausea, vomiting, diarrhea, lymphadenopathy, and shortness of breath without cough or chest pain. Chest radiography revealed bilateral interstitial infiltrates. Her medical history was remarkable for infectious mononucleosis 5 years earlier and recurrent sore throats. She had had cystitis once within the past 2 years. Her only medication was birth control pills. She denied ever having a sexually transmitted disease. She had been sexually active with 6 partners during her life, including 2 in the month before becoming ill.
On physical examination, her temperature was 39.2°C, blood pressure, 112/78 mm Hg; pulse, 110 beats per minute; and respirations, 28 breaths per minute. Notable physical findings included enlarged tonsils and a white exudate on the right tonsil. She did not have thrush or hairy leukoplakia. Her only lymph node abnormality was a tender 2-cm node in the left occipital chain. She had basilar rales and rhonchi (abnormal sounds accompanying breathing). A slightly tender liver with a span of 12 cm was palpable at the right costal margin. The splenic tip could not be felt. The rest of the examination findings were unremarkable. Her CBC was normal except for a platelet count of 50,000/mm3 and a CD4 T-cell count of 250 cells/mm3 (CD8 T-cell count was 580 cells/mm3). HIV serologic testing by enzyme immunoassay was negative, but a p24 antigen level was greater than 5000 pg/mL. Her HIV RNA level was 3.5 million copies/mL. A later Western blot was indeterminate, with bands at p24 and p55.
During a 3-week hospital stay, the patient underwent numerous tests and procedures. Bronchoscopy and open-lung biopsy revealed interstitial pneumonitis with lymphocytes and plasma cells. Pathologic sections showed evidence of cytomegalovirus inclusions, although viral cultures remained negative. All cultures from blood and from respiratory and pulmonary specimens remained negative. When the patient did not respond to intravenous erythromycin and cefixime, she was treated with intravenous ganciclovir for 3 weeks. Her temperature gradually declined, and her pulmonary symptoms resolved. By the time she was discharged, repeat HIV serologic testing showed positive ELISA and Western blot with bands at p17, p24, p31, p66, gp120, and gp160. Her plasma p24 antigen level had declined to 60 pg/mL. The HIV RNA level remained elevated at 474,281 copies/mL.
She was followed up in the HIV outpatient clinic. On the basis of her persistently elevated HIV viral level, she was started on 600 mg of oral zidovudine daily, 150 mg of lamivudine twice a day, and 600 mg of ritonavir twice a day. After 2 months on this triple regimen, she remained asymptomatic, and her HIV RNA level had become undetectable.
*Special thanks to Roberto Arduino, M.D., and Aga Kuliev, M.D., for providing this case report.
**Adapted from: Quinn T. C. Acute primary HIV infection. JAMA. 1997;278:58-62.
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