Pediatric HIV Infection Differential Diagnoses

Sections

DDx

Diagnostic Considerations

Older children and young teenagers can have human immunodeficiency virus (HIV) infection or AIDS without a history of immunodeficiency or severe illness. Fever of unknown origin, recurrent infection, growth failure, or developmental regression without an obvious etiology should increase the index of suspicion for HIV infection.

The failure to complete neonatal testing is another pitfall. The process to verity that an at-risk neonate does not have HIV infection is complex. Too often, follow-up tests are not performed if initial results are negative.

Prenatal HIV tests are often performed, but the results may not be followed up, especially in low-risk women.

Nonopportunistic infections

Like most children, children with HIV are susceptible to common pathogens. Diseases caused by such pathogens should be high in the list of differential diagnoses for these children. Of course, the particular child's medical history guides the differential diagnosis. For example, chronic lung disease requires special consideration of atypical respiratory pathogens, such as Pseudomonas or Xanthomonas species.

One of the challenges with children who are infected with HIV is that they are more likely than others to have recurrent infections, which cause them to undergo repeat treatment with many broad-spectrum antibiotics. This antibiotic exposure increases the risk of their developing resistant pathogens. Therefore, infection with penicillin-resistant pneumococci is not uncommon in children with recurrent ear infections.

Common recurrent infections are otitis, sinusitis, and pneumonia. Recurrent otitis is observed in 55% and 35% of HIV-infected children with AIDS and those without AIDS, respectively.

Children with recurrent bacterial infections and CD4⁺ counts of less than 200 X 10⁹/L may benefit from monthly IVIG.

Moderate and severe neutropenia increases the risk for bacterial infection by 2.3- and 7.9-fold, respectively. Other risk factors for bacterial infection include neutropenia within the last 3 months and central venous line access.

Differential Diagnoses

Workup

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Genome layout of human immunodeficiency virus (HIV)–1 and HIV-2.

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Table 1. CDC Immunologic Categories for HIV-Infection in Children Based on Absolute CD4 ⁺ Counts

Category
Category	< 1 y	1-5 y	6-12 y
1 - No suppression	≥1500 (>25)	≥1000 (>25)	≥500 (>25)
2 - Moderate suppression	750-1499 (15-24)	500-999 (15-24)	200-499 (15-24)
3 - Severe suppression	< 750 (< 15)	< 500 (< 15)	< 200 (< 15)

Table 2. Antibiotics for Primary and Secondary Prophylaxis of Opportunistic Infections

Infection	Indication	First-Line Regimen	Alternative Regimen
TB	PPD test result >5 mm	Isoniazid and pyridoxine qd for 9 mo	Rifampin for 4 mo
TB	Exposure	Isoniazid and pyridoxine 3 times/wk for 9 mo, rifampin and pyrazinamide qd for 2 mo	Consult an infectious diseases specialist if the pathogen is multidrug resistant
PCP	CD4⁺ finding*	Trimethoprim-sulfamethoxazole qd	Trimethoprim-sulfamethoxazole 3 times/wk
	Fever of unknown origin for 2 wk, history of infection	Dapsone, pyrimethamine, and leucovorin	Dapsone or aerosolized pentamidine in children >5 y
	---	Atovaquone	Atovaquone
Toxoplasmosis	CD4⁺ count < 100 cells/mL	Trimethoprim-sulfamethoxazole qd	Dapsone, pyrimethamine, and leucovorin
	Positive immunoglobulin G finding	None	Atovaquone
	Previous infection	Sulfadiazine, pyrimethamine, and leucovorin	Clindamycin, pyrimethamine, and leucovorin
MAC infection	CD4⁺ finding^**	Azithromycin qwk	Rifabutin qd or clarithromycin bid
MAC infection	Previous infection	Clarithromycin or azithromycin qd and ethambutol	Clarithromycin or azithromycin qd and ethambutol
Abbreviations: bid = twice daily; PPD = purified protein derivative; qd = every day; qwk = every week. ^* See Table 4 **See Table 5

Table 3. Drugs and Doses for Prophylaxis of Opportunistic Infections

Drug	Dose
Azithromycin	20 mg/kg/dose (1.2 g maximum) PO qwk or 5 mg/kg/dose (250 mg maximum) PO qd
Clarithromycin	7.5 mg/kg/dose (500 mg maximum) PO bid
Clindamycin	20-30 mg/kg/d PO qid
Dapsone	1-2 mg/kg/d (100 mg maximum) PO qd
Ethambutol	15 mg/kg/dose (900 mg maximum) PO qd
Isoniazid	10-15 mg/kg/dose (300 mg maximum) PO/IM qd
Leucovorin	5 mg PO 3 times/wk
Pentamidine	4 mg/kg/dose monthly
Pyrimethamine	15 mg/m²/dose (25 mg maximum) PO qd
Rifabutin	5 mg/kg/dose (300 mg maximum) PO qd
Rifampin	10-20 mg/kg (600 mg maximum) PO/IV qd
Sulfadiazine	85-120 mg/kg/d PO bid
Trimethoprim-sulfamethoxazole	150/750 mg/m²/d PO bid
Abbreviations: bid = twice daily; PO = by mouth; qd = every day; qwk = every week.

Table 4. CD4 ⁺ -Based Indications for Starting PCP Prophylaxis

Age or Status	CD4⁺ Count, cells/mL	CD4⁺ Percentage
6 wk to 1 y	Any	Any
1-2 y	< 750	< 15
2-5 y	< 500	< 15
>5 y	< 200	< 15
Previous PCP infection	Any	Any

Table 5. CD4 ⁺ -Based Indications for MAC Prophylaxis

Age or Status	CD4⁺ Count, Cells/mL
< 1y	< 750
1-2 y	< 500
2-6 y	< 75
> 6 y	< 50
Previous infection	Any

Table 6. Risk Factors for Vertical Transmission

Period	Factors That Increase Risk	Factors That Decrease Risk
Prenatal	Acute HIV infection Viral load >10,000 Cigarette smoking Illicit IV drug use	Viral load < 1000 Zidovudine treatment Neutralizing antibodies
Perinatal	Rupture of membranes for >4 h Chorioamnionitis Emergency cesarean delivery Surgical delivery Episiotomy Use of scalp electrodes	Elective cesarean delivery with zidovudine treatment
Neonatal	Prematurity Low birth weight First-born twin	Full-term Second-born twin
Postdelivery	Breastfeeding	ART

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Author

Delia M Rivera, MD Assistant Professor, Department of Pediatrics, Division of Infectious Disease and Immunology, University of Miami Leonard M Miller School of Medicine

Delia M Rivera, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Coauthor(s)

Richard E Frye, MD, PhD Professor of Child Health, University of Arizona College of Medicine at Phoenix; Chief of Neurodevelopmental Disorders, Director of Autism and Down Syndrome and Fragile X Programs, Barrow Neurological Institute at Phoenix Children's Hospital

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Mark Abdelmalek, MD Chief, Division of Laser and Dermatologic Surgery, Assistant Professor, Department of Dermatology, Drexel University College of Medicine

Mark Abdelmalek, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Medical Association, American Society for Dermatologic Surgery, Pennsylvania Academy of Dermatology, and Pennsylvania Medical Society