Human Immunodeficiency Virus Infection
- HIV is the etiologic agent of AIDS. HIV suppresses CD4+ T cells leading to impaired cell-mediated immunity.
- HIV-1 is more common worldwide, whereas HIV-2 is mainly prevalent in West Africa.
- 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), 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 the infected individual will experience progressive immunologic deterioration and eventually become susceptible to opportunistic infections and cancers.
- As of 2015, there were an estimated 36.7 million people living with HIV worldwide, and as of 2013, 1.3 million in the United States. The highest prevalence of HIV is in Sub-Saharan Africa.
- In 2015, there were 39,513 new HIV diagnoses in the United States, 120 in those <13 years of age and 8,737 in those between the ages of 13- to 24 years Centers for Disease Control and Prevention (CDC).
- In 2015, approximately 90% of new diagnoses among 13 to 24-year-old men had male-to-male sex as the primary risk factor.
- African American individuals made up approximately 55% of new diagnoses in 2015 among those 13 to 24 years old.
- 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., needle stick): 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 an HIV-infected mother (not on treatment) giving birth to an infected infant 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 <2%.
- 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.
- Breastfeeding is not recommended in the United States.
- HIV is not believed to be transmitted by the following:
- 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
- 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 two to three drugs is recommended. One regimen consists of zidovudine for 6 weeks, plus nevirapine given in 3 doses (at birth, 48 hours after the first dose, and 96 hours after second dose). Some experts recommend a three-drug regimen with the addition of lamivudine to zidovudine and nevirapine. However, the optimal duration of nevirapine and lamivudine is not known with guidelines stating a range of 2 to 6 weeks.
- 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
- Daily tenofovir/emtricitabine approved by the U.S. Food and Drug Administration (FDA) for patients 18 years and older
- 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
Clinical signs, symptoms, and scenarios in which HIV testing should be performed:
- Infants with maternal HIV status that is unknown or positive
- 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 jiroveci 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
- 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
- Neoplastic disease
- Histiocytosis X
- Congenital/perinatal cytomegalovirus
- Congenital syphilis
- Acquired Epstein-Barr virus
- Congenital immunodeficiency syndromes
- Wiskott-Aldrich syndrome
- Chronic granulomatous disease
Diagnostic Tests and Interpretation
- Infants with perinatal HIV exposure
- Virologic testing using HIV RNA and 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 nonbreastfed infant is defined as two or more negative virologic tests with one obtained at >1 month and one at >4 months or two 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 HIV-infected infants 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/HIV-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% 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 are associated with poor short-term (2 to 5 years) 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.
Failure to screen for HIV infection during pregnancy results in inability to offer ART during pregnancy, which may lead to failure of preventing infant infection, as well as the inability to prescribe Pneumocystis jiroveci pneumonia prophylaxis to infected newborns.
- Active immunizations
- All infected children receive standard childhood immunizations, including the pneumococcal conjugate vaccine.
- Infected children 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: One of the major advances has been the ability to offer prophylaxis against the most common opportunistic infections.
- Prophylaxis against Pneumocystis pneumonia with TMP-SMX is indicated for all HIV-infected infants 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.
- 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 therapy (usually three or more drugs), termed highly active antiretroviral therapy (HAART). There are now five different drug classes and as multiple multiclass combination pills.
- 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.
- Family psychosocial support is critical.
- All infected patients 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), virologic suppression (quantitative plasma viral RNA), and medication safety.
Due to HAART, 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 of untreated HIV include:
- Pneumocystis jiroveci pneumonia
- Most common early fatal illness in HIV-infected children (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 M. 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 HIV-infected children 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
- American Academy of Pediatrics. Human immunodeficiency virus infection. In: Kimberlin DW, Brady MT, Jackson MA, et al, eds. Red Book: 2015 Report of the Committee on the Infectious Disease. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed April 15, 2018.
- Panel on Antiretroviral Therapy and Medical Management of Children Infected with HIV. Guidelines for the use of antiretroviral agents in pediatric HIV infection. http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Accessed April 15, 2018.
- Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed April 15, 2018.
- Rakhmanina N, Phelps BR. Pharmacotherapy of pediatric HIV infection. Pediatr Clin North Am. 2012;59(5):1093–1115. [PMID:23036246]
- U.S. Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States—2014. https://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf. Accessed April 15, 2018.
- 042 Human immunodeficiency virus [HIV] disease
- V08 Asymptomatic human immunodeficiency virus [HIV] infection status
- 795.71 Nonspecific serologic evidence of human immunodeficiency virus [HIV]
- 079.53 Human immunodeficiency virus, type 2 [HIV-2]
- 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
- 86406008 human immunodeficiency virus infection (disorder)
- 165816005 Human immunodeficiency virus positive (finding)
- 405631006 Pediatric human immunodeficiency virus infection (disorder)
- 79019005 human immunodeficiency virus II infection (disorder)
- 40780007 Human immunodeficiency virus I infection (disorder)
- Q: Should HIV-positive mothers breastfeed?
- A: The recommendation for HIV-positive mothers in resource-rich areas is to NOT breastfeed, as breastfeeding poses continued risk of exposure and infection with HIV to the infant. In areas where there are no affordable and safe substitutes of breastfeeding, exclusive breastfeeding is advised.
- Q: What are the recommendations for HIV screening in adolescents?
- A: The CDC recommend routine HIV testing for individuals aged 13 to 65 years. As part of anticipatory guidance, the American Academy of Pediatrics recommends offering HIV testing for adolescents aged 16 to 18 years of age at least once if prevalence of HIV in the area is >0.1%. Continued HIV screening is also recommended for youth with high-risk behavior and those undergoing STI evaluations.
David C. Griffith, MD
Allison L. Agwu, MD, ScM
© Wolters Kluwer Health Lippincott Williams & Wilkins
Human Immunodeficiency Virus Infection
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