Since the first cases of human immunodeficiency virus (HIV) infection were identified, the number of children infected with HIV has risen dramatically in developing countries, the result of an increased number of HIV-infected women of childbearing age in these areas. HIV is a retrovirus and can be transmitted vertically, sexually, or via contaminated blood products or IV drug abuse. Vertical HIV infection occurs before birth, during delivery, or after birth.

The genome layouts of HIV-1 and HIV type 2 (HIV-2) are shown in the image below.

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

Essential update: Study suggests benefits to starting HAART earlier in HIV-infected children

In a study of HIV-1-infected, highly active antiretroviral therapy (HAART)-naive children, Yin et al found that beginning HAART at younger ages and healthier CD4 levels results in better immune recovery. ^{[1, 2]} In all, 72% of children who were immunosuppressed at baseline recovered to normal within 4 years after initiating HAART therapy. Compared with children with severe immunosuppression, more children with mild immunosuppression (+36%) or advanced immunosuppression (+20.8%) recovered a normal CD4 percentage.

For every 5-year increase in baseline age, the proportion of children who achieved a normal CD4 percentage fell by 19%. ^[2] Combining age effects and baseline CD4 percentage resulted in more than 90% recovery when HAART was initiated in children with mild immunosuppression at any age or advanced immunosuppression at an age younger than 3 years. Most of the immunologic benefits of HAART remained significant at 4 years.

Signs and symptoms

History

Signs and symptoms of pediatric HIV infection include the following:

• Unusually frequent and severe occurrences of common childhood bacterial infections, such as otitis media, sinusitis, and pneumonia
• Recurrent fungal infections, such as candidiasis (thrush), that do not respond to standard antifungal agents: Suggests lymphocytic dysfunction
• Recurrent or unusually severe viral infections, such as recurrent or disseminated herpes simplex or zoster infection or cytomegalovirus (CMV) retinitis; seen with moderate to severe cellular immune deficiency
• Growth failure
• Failure to thrive
• Wasting
• Failure to attain typical milestones: Suggests a developmental delay; such delays, particularly impairment in the development of expressive language, may indicate HIV encephalopathy
• Behavioral abnormalities (in older children), such as loss of concentration and memory, may also indicate HIV encephalopathy

Physical examination

Signs and symptoms of pediatric HIV infection found during physical examination include the following:

• Candidiasis: Most common oral and mucocutaneous presentation of HIV infection
• Thrush in the oral cavity and posterior pharynx: Observed in approximately 30% of HIV-infected children
• Linear gingival erythema and median rhomboid glossitis
• Oral hairy leukoplakia
• Parotid enlargement and recurrent aphthous ulcers
• Herpetic infection with herpes simplex virus (HSV): May manifest as herpes labialis, gingivostomatitis, esophagitis, or chronic erosive, vesicular, and vegetating skin lesions; the involved areas of the lips, mouth, tongue, and esophagus are ulcerated
• HIV dermatitis: An erythematous, papular rash; observed in about 25% of children with HIV infection
• Dermatophytosis: Manifesting as an aggressive tinea capitis, corporis, versicolor, or onychomycosis
• Pneumocystis jiroveci (formerly P carinii) pneumonia (PCP): Most commonly manifests as cough, dyspnea, tachypnea, and fever
• Lipodystrophy: Presentations include peripheral lipoatrophy, truncal lipohypertrophy, and combined versions of these presentations; a more severe presentation occurs at puberty
• Digital clubbing: As a result of chronic lung disease
• Pitting or nonpitting edema in the extremities
• Generalized cervical, axillary, or inguinal lymphadenopathy

Diagnosis

Detection of antibody to HIV is the usual first step in diagnosing HIV infection. The 2010 Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children ^[3] recommendations for diagnosing infants include the following:

• Because of the persistence of the maternal HIV antibody, infants younger than 18 months require virologic assays that directly detect HIV in order to diagnose HIV infection
• Preferred virologic assays include HIV bDNA polymerase chain reaction (PCR) and HIV RNA assays. The HIV PCR DNA qualitative test is usually less expensive.
• Further virologic testing in infants with known perinatal HIV exposure is recommended at 2 weeks, 4 weeks, and 4 months

An antibody test to document seroreversion to HIV antibody–negative status in uninfected infants is no longer recommended.

In older children and adults, an enzyme-linked immunosorbent assay (ELISA) to detect HIV antibody, followed by a confirmatory Western blot (which has increased specificity), should be used to diagnose HIV infection.

Rapid HIV tests, which provide results in minutes, simplify and expand the availability of HIV testing. Their sensitivity is as high as 100%, but they must be followed with confirmatory Western blotting or immunofluorescence antibody testing, as with conventional HIV antibody tests.

Management

Appropriate ART and therapy for specific infections and malignancies are critical in treating patients who are HIV positive. Classes of antiretroviral agents include the following:

• Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)
• Protease inhibitors (PIs)
• Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
• Fusion inhibitors
• CCR5 coreceptor antagonists (entry inhibitors)
• HIV integrase strand transfer inhibitors

Combination ART with at least 3 drugs from at least 2 classes of drugs is recommended for initial treatment of infected infants, children, and adolescents because it provides the best opportunity to preserve immune function and delay disease progression. Drug combinations for initial therapy in ART-naive children include a backbone of 2 NRTIs plus 1 NNRTI or 1 PI.

Pediatric HIV experts agree that infected infants who have clinical symptoms of HIV disease or evidence of immune compromise should be treated. ^[3] Patients aged 1 year or older with acquired immunodeficiency syndrome (AIDS) or significant symptoms should be aggressively treated regardless of CD4⁺ percentage and count or plasma HIV RNA level.

In addition to antiretroviral drugs (ARDs), other types of medication are required as appropriate for specific infections or malignancies. For example, P jiroveci pneumonia prophylaxis is recommended in patients who are HIV positive and younger than 1 year and in older children based on CD4⁺ counts.