DESCRIPTION

• Human immunodeficiency virus (HIV) is the etiologic agent of acquired immunodeficiency syndrome (AIDS). HIV suppresses CD4+ T cells leading to impaired cell-mediated immunity.
  • An acute phase with flulike symptoms develops 2 to 4 weeks after acquiring infection, followed by a long asymptomatic period (5 to 15 years in adults, shorter in children).
  • This phase is followed, if untreated, by development of nonspecific signs and symptoms (weight loss, adenopathy, hepatosplenomegaly, failure to thrive) and clinical immunodeficiency.
• AIDS is the advanced stage of untreated HIV when an individual with HIV will experience progressive immunologic deterioration and eventually become susceptible to opportunistic infections and cancers.

EPIDEMIOLOGY

• HIV-1 is more common worldwide, whereas HIV-2 is mainly prevalent in West Africa.
• Prevalence: As of 2021, there were an estimated 38.4 million people living with HIV worldwide, and as of 2019, 1.2 million in the United States. The highest prevalence of HIV is in sub-Saharan Africa.
• Incidence: In 2019, there were approximately 36,000 new HIV diagnoses in the United States, 61 in those <13 years of age, and 7,600 in those between the ages of 13 and 24 years.
• In 2019, approximately 83% of new diagnoses among 13- to 24-year-olds had male-to-male sex as the primary risk factor.

RISK FACTORS

• Sexual contact
  • Unprotected orogenital, vaginal, or anal sex: Anal receptive sex is highest risk.
• Exposure to infected blood or body fluids
  • Needle sharing (injection drug use)
  • Occupational exposure (i.e., needlestick): Risk of transmission from an HIV-contaminated needle is 1:300.
  • Blood transfusion: All donated blood in the United States is screened for HIV.
  • Mucous membrane exposure to infected blood or fluids
• Perinatal infection can occur either in utero or during labor and delivery.
  • Risk of a mother with HIV (not on treatment) giving birth to an infant with infection is ~20% (in the absence of breastfeeding), with increased rate of transmission for women with low CD4 counts or higher viral titers. Vaginal delivery, especially with rupture of membranes >8 hours, appears to increase the risk of infant infection.
  • Risk of perinatal transmission if mother is effectively treated (undetectable viral load) is <1%.
  • Presence of untreated sexually transmitted infections (STIs), chorioamnionitis, and prematurity all increase the risk of mother-to-child transmission of HIV.
• Breast milk
  • Overall risk of breastfeeding is ~15%.
  • In countries where breastfeeding is the norm, up to 30% of perinatally acquired HIV infections occur through breastfeeding.
  • U.S. guidelines recommend against breastfeeding given ongoing risk of HIV exposure. However, individuals who chose to breastfeed should be supported in risk-reduction measures to minimize transmission (i.e., maintaining undetectable viral load, extended infant prophylaxis, exclusive breastfeeding).
• HIV is not believed to be transmitted by the following:
  • Bites
  • Sharing utensils, bathrooms, bathtubs
  • Exposure to urine, feces, vomitus (except where these fluids may be grossly contaminated with blood, and even then, transmission is rare, if it happens at all)
  • Casual contact at home, school, or day care center

GENERAL PREVENTION

• Prevention of mother to child transmission: All pregnant women should be offered HIV testing at the first prenatal visit. In areas of high incidence, repeat testing should be done at 36 weeks of gestation. Women not tested before or during labor should undergo expedited HIV testing.
  • Antenatal three-drug antiretroviral therapy (ART) for all HIV-positive pregnant women
  • Delivery via elective cesarean section for selected cases
  • Postnatal ART prophylaxis for infants:
    • 4-week course of zidovudine for low-risk mothers (on ART with suppressed viral load)
    • For high-risk mothers (not on ART or on ART but with elevated viral load) combination ART with three drugs is recommended: zidovudine and lamivudine along with either nevirapine or raltegravir for 6 weeks
    • Some experts recommend a two-drug prophylaxis with zidovudine plus nevirapine regimen depending on the risk.
• Postexposure prophylaxis
  • ART initiated after possible HIV exposure: unprotected sex or sexual assault, needle sharing, occupational exposure
  • Consists of three-drug ART for 28 days
  • Must be initiated within 72 hours of exposure
• Preexposure prophylaxis (PrEP)
  • Approved for HIV prevention by the U.S. Food and Drug Administration (FDA) for adolescents and adults
  • Daily emtricitabine/tenofovir disoproxil approved for most healthy individuals; emtricitabine/tenofovir alafenamide approved for men and transgender women at sexual risk for HIV; long-acting injectable cabotegravir was approved for PrEP in 2021.
  • Recommended for high-risk individuals: men who have sex with men or heterosexual men/women with HIV-positive partners, multiple sexual partners, recent STI and injection drug users who share injection equipment.
• General measures: condom use, avoidance of needle sharing, no breastfeeding (or breastfeeding with risk reduction measures)

HISTORY

Clinical signs, symptoms, and scenarios in which HIV testing should be performed:

• Infants with maternal HIV status that is unknown or positive
• Children of newly diagnosed women for whom HIV acquisition could have been during prior pregnancy
• All adolescents (particularly those endorsing sexual activity) at least annually
• Patients who use drugs (injectable or noninjectable)
• History of STIs, especially syphilis
• Patients presenting with opportunistic infections (i.e., Pneumocystis pneumonia, recurrent or resistant thrush, especially after 12 months of age)
• Infants with congenital syphilis, acquired microcephaly, progressive encephalopathy, loss of developmental milestones, failure to thrive, delayed puberty
• Patients with recurrent/chronic diarrhea, recurrent/chronic parotid gland enlargement, generalized lymphadenopathy

PHYSICAL EXAM

• Perinatally acquired HIV
  • May be normal in the 1st months of life
  • 90% have exam findings by 2 years of age.
  • Most common findings are generalized adenopathy, hepatosplenomegaly, failure to thrive, recurrent/resistant thrush (especially after 1 year of age).
  • Recurrent or chronic parotitis
• Nonperinatally acquired HIV
  • Generally nonspecific: lymphadenopathy, weight loss, evidence of opportunistic infection

DIFFERENTIAL DIAGNOSIS

• Neoplastic disease
  • Lymphoma
  • Leukemia
  • Histiocytosis X
• Infectious
  • Congenital/perinatal cytomegalovirus
  • Toxoplasmosis
  • Congenital syphilis
  • Acquired Epstein-Barr virus
• Congenital immunodeficiency syndromes
  • Wiskott-Aldrich syndrome
  • Chronic granulomatous disease

DIAGNOSTIC TESTS & INTERPRETATION

• Infants with perinatal HIV-exposure
  • Virologic testing using HIV RNA or DNA polymerase chain reaction (PCR) tests are recommended at birth, 14 to 21 days, 1 to 2 months (preferably 2 to 4 weeks after cessation of antiretroviral prophylaxis), and 4 to 6 months.
    • Negative testing in a non-breastfed infant is defined as 2 or more negative virologic tests, with 1 obtained at >1 month and 1 at >4 months, or 2 negative antibody tests obtained >6 months of age.
    • Both HIV RNA and DNA PCR have sensitivities and specificities >95% after 2 weeks of age.
    • By 1 month of age, 95% of infants with HIV will have positive HIV DNA PCR.
    • Residual maternal antibodies may be detected up to 24 months.
• For those >2 years of age
  • HIV-1/HIV-2 antigen/antibody combination qualitative immunoassay simultaneously detects presence of HIV p24 antigen and HIV 1/2 antibodies
    • p24 antigen component allows for detection 2 to 3 weeks after infection and can help identify patients with acute HIV infection.
• CD4 counts
  • Obtained at diagnosis and routinely
  • Results need to be evaluated based on age-adjusted normal values. Absolute CD4 counts are elevated in childhood, with normal median values >3,000/mm³ in the 1st year of life, which then gradually decline with age, reaching values comparable with adult levels (800 to 1,000/mm³) by age 7 years.
  • For children <5 years of age, CD4 percentage should be used instead of absolute CD4 count.
• Quantitative viral RNA PCR assays
  • Termed “viral loads,” results are reported in a range from undetectable, usually <20 copies/mL (cpm), to upper values of >10 million cpm.
  • Viral loads that remain >100,000 cpm are associated with poor short-term (2- to 5-year) outcomes.
  • Also used as a marker of efficacy of treatment; goal is to suppress viral replication to the undetectable range for as long as possible.
  • Test is done at time of diagnosis to establish baseline and routinely to assess treatment adherence/efficacy.
• Other frequent lab abnormalities include thrombocytopenia, anemia, and elevated liver enzymes.

GENERAL MEASURES

• Active immunizations
  • All children with HIV receive standard childhood immunizations, including the pneumococcal conjugate vaccine.
  • Children with HIV should receive yearly influenza A/B immunizations and 23-valent pneumococcal vaccine at age 2 years.
  • Symptomatic children should not receive the varicella vaccine, and those with severely low CD4 counts should not receive measles-mumps-rubella vaccination.
• Prophylaxis:
  • Prophylaxis against Pneumocystis pneumonia with trimethoprim (TMP)-sulfamethoxazole (SMX) is indicated for all infants with HIV between 4 to 6 weeks and 12 months of age, for those 1 to 6 years of age with CD4 count <500 cells/mm³ or <15%, and for children >6 years of age with CD4 <200 cells/mm³ or <15%.
  • Prophylaxis against toxoplasmosis and mycobacterium avium complex is indicated in children with severe immune suppression.

MEDICATION

ART

• Specific combination ART prolongs life, delays progression of illness, promotes improved growth, and improves neurologic outcome.
• Standard of care now involves the administration of combination ART therapy (usually 3 drugs). There are now multiple multiclass combination single-tablet regimens.
• Given the complexities of therapy, ART should always be prescribed in consultation with a specialist in pediatric/adolescent HIV infection.
• Adherence to prescribed schedules is critical. When patients miss even 10–20% of doses, the durability of response is short.

FOLLOW-UP RECOMMENDATIONS

• Family psychosocial support is critical.
• All individuals with HIV should be comanaged with an HIV specialty care site.
• Patients should be seen every 1 to 3 months to monitor adherence, immune status (CD4 counts), and virologic suppression (quantitative plasma viral RNA), and medication safety.

PROGNOSIS

Due to ART, morbidity and mortality have both greatly decreased:

• Median survival is now into adulthood.
• Incidence of new opportunistic infections (AIDS-defining illnesses) has decreased greatly, as have hospital admissions.

COMPLICATIONS

Complications of untreated HIV include the following:

• Pneumocystis pneumonia
  • Most common early fatal illness in children with HIV (peak age 3 to 9 months) mortality is 30–50%. A high index of suspicion is necessary for prompt diagnosis (by lavage) and initiation of therapy.
• Lymphocytic interstitial pneumonitis
  • Chronic respiratory disorder that causes a distinctive diffuse reticulonodular pattern on chest radiographs, usually diagnosed between 2 and 4 years of age
• Recurrent invasive bacterial infections
  • Bacterial pneumonia, sinusitis, and otitis media are common.
• Progressive encephalopathy
  • Diagnosed between 9 and 18 months of age, the hallmark is progressive loss of milestones or neurologic dysfunction.
• Disseminated Mycobacterium avium intracellulare
  • Older children, usually >5 years of age, with severe immunodeficiency (CD4 ≤100 cells/mm³)
  • Symptoms include prolonged fevers, abdominal pain, anorexia, and diarrhea.
• Candida esophagitis:
  • Older children with severe immunodeficiency usually present with dysphagia or chest pain and oral thrush.
• Disseminated cytomegalovirus disease
  • Retinitis less common in children with HIV than in adults
  • Cytomegalovirus may also cause pulmonary disease, colitis, and hepatitis.
• HIV-related cancers
  • Non-Hodgkin lymphoma most common cancer, with primary site usually located in the CNS.
• Other organ dysfunction associated with HIV infection in children: cardiomyopathy, hepatitis, renal disease, thrombocytopenia, idiopathic thrombocytopenic purpura

ICD 10

• B20 Human immunodeficiency virus [HIV] disease
• Z21 Asymptomatic human immunodeficiency virus infection status
• R75 Inconclusive laboratory evidence of human immunodef virus
• B97.35 HIV 2 as the cause of diseases classified elsewhere