eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

HIV Infection

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
Coauthor(s): Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
Contributor Information and Disclosures

Updated: Jan 20, 2010

Introduction

Background

Over the past 25 years, since the first cases of what is now recognized as human immunodeficiency virus (HIV) infection were identified in 1981, the number of children infected with HIV has increased dramatically in developing countries because the number of HIV-infected women of childbearing age has risen. However, great advances have been made in the United States and in other industrialized nations to control transmission of the virus from mother to infant.

In the United States, universal prenatal HIV testing has been recommended to obstetricians since 1995. However, this testing was not mandatory in all states. In September 2006, the Centers for Disease Control and Prevention (CDC) released its Revised Recommendations for HIV Testing of Adults Adolescents, and Pregnant Women in Health-Care Settings. These new recommendations, which replaced its 1993 Recommendations for HIV Testing Services for Inpatients and Outpatients in Acute Care Hospital Settings, advise routine HIV screening for adults, adolescents, and pregnant women in healthcare settings in the United States. They also recommend reducing barriers to HIV testing.

Before prenatal testing was common, diagnosing HIV infections in a woman after diagnosing it in her child was not unusual, and the diagnosis of acquired immunodeficiency syndrome (AIDS) in a previously healthy child was not rare.

Before 1985, one way in which children were infected was the transfusion of blood-products. Improved screening tests have eliminated such transmission. A common way adolescents become infected is by engaging in high-risk behaviors such as unprotected intercourse, male homosexual intercourse, and intravenous (IV) drug abuse

In pediatric patients, HIV infection progresses as it does in adults, although recent surveillance data from CDC suggests that patients who are aged 13-24 years when AIDS is diagnosed survive longer than older individuals do. Vertically transmitted HIV can cause rapidly progressive, chronically progressive, or adultlike disease in which a significant clinical latency period occurs before symptoms appear.

Pathophysiology

After HIV enters a host, trimeric gp120 glycoproteins that protrude from its lipoprotein bilayer envelope bind to CD4 cell-surface receptors and CCR5 or CXCR4 chemokine co-receptors. CD4 receptors are located on CD4⁺ T lymphocytes, monocytes, and macrophages. Juxtapositioned co-receptors are also needed for viral infection. The V3 region of the gp120 glycoprotein determines cellular tropism, and tropism is involved in syncytial formation. M-tropic (nonsyncytial) strains prefer the CCR5 co-receptor and are the primary causes of infection. Deficiency of CCR5 chemokine co-receptors is present in as many as 10% of Europeans and 20% of Ashkenazi Jews, and it appears to confer some protection against infection. After gp120 binds to the receptors, an associated gp41 transmembrane glycoprotein is inserted into the cell membrane and initiates cell-membrane fusion.

Upon entering the cell, the protease enzyme produces the reverse transcriptase and ribonuclease (RNAse) H enzymes responsible for synthesizing the single-stranded DNA (ssDNA) molecules and primers necessary to produce the complementary DNA strand. Because reverse transcriptase lacks proofreading machinery, considerable base-to-base variability results. The high mutation rate, combined with the high reproductive rate, results in substantial evolution and subsequent resistance to treatment.

Acute infection rapidly increases the viral load and causes a mild-to-moderate viremia. Although viral loads tend to diminish rapidly after acute infection in adults, they slowly decrease in vertically infected children and may not reach baseline levels until the children aged 4-5 years. Although infants possess numerous antigen-presenting and effector cells compared with adults, their cytokine production, proliferation, and cytotoxicity are reduced.

Envelope-specific cytotoxic T lymphocytes are less common in children who vertically acquire the disease than in children who acquire HIV by means of blood transfusion. Among those with vertically acquired disease, lymphocytes are least common in those with rapidly progressing disease. Precursors of cytotoxic T-lymphocyte that are specific to HIV type 1 (HIV-1) do not develop in significant number until the child is aged 1 year. In adults, antibodies to gp120 develop several months after the initial viremia occurs. The development of broadly neutralizing antibodies is associated with slowed disease progression in adults, children, and infants.

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

Frequency

United States

In 2002, an estimated 144-246 infants acquired HIV infection by means of vertical (mother-to-infant) transmission.¹ Estimates from 1991 placed the peak of perinatally-transmitted HIV at 1651.

The HIV seroprevalence rate in pregnant women is as high as 0.3%. The seroprevalence of women infected with HIV is highest in the Northeast, followed by the South. Perinatal HIV transmission rates are 25% but as low as 2% in untreated women with viral loads of less than 100 copies/mL.

Although prophylactic interventions have reduced vertical transmissions, cases of perinatal HIV transmission continue to occur.² This is largely because of missed opportunities for prevention, particularly among women who lack prenatal care or who are not being offered voluntary HIV counseling and testing during pregnancy. In many as 40% of the mothers of infants with perinatally acquired HIV infection, the HIV infection was not known before delivery.

In the United States, HIV infection is the 14th leading cause of death in young children. In 2004, 61 children with AIDS younger than 13 years died.³ Minority populations are overrepresented in this epidemic, and HIV infection is the 7th cause of death in the black population. In the United States, most children with AIDS live in metropolitan areas.

HIV-1 is the most common cause of HIV infection in the Americas, in Europe, in Asia, and in Africa. HIV-1 subtypes differ by geographic region. HIV-1 subtype B is predominant in the United States, though non-B subtype HIV-1 infections are increasing.

International

Almost 40 million individuals are infected with HIV worldwide, and 90% of them are in developing countries. HIV has infected 4.4 million children and has resulted in the deaths of 3.2 million. Each day, 1800 children—the vast majority newborns—are infected with HIV. Approximately 7% of the population in sub-Saharan Africa is infected with HIV; these individuals represent 64% of the world's HIV-infected population. Furthermore, 76% of all women infected with HIV live in this region.

The HIV seroprevalence rate among pregnant women in South America is 0.3-5%; in sub-Saharan Africa, the range is 13-45%. In Europe, the HIV seroprevalence is greatest in western countries; France, Spain, and Italy have the highest incidences. Pregnant women in urban areas of these countries have a seroprevalence rate as high as 1%. Nonetheless, the epidemics in Eastern Europe and in Central Asia continue to grow; the number of people living with HIV in these regions reached an estimated 1.6 million in 2005—an increase of almost 20-fold in less than 10 years. The overwhelming majority of these people living with HIV are young; 75% of infections reported between 2000 and 2004 were in people younger than 30 years. In Western Europe, the corresponding percentage was 33%.

The magnitude of the AIDS epidemic in Asia is significant. Although national HIV infection levels are low in Asia compared with other continents (notably Africa), the populations of many Asian nations are so large that even low prevalences reflect large numbers of people are living with HIV. The seroprevalence rate in pregnant women is already 2%, and the vertical transmission rate is 24% without breastfeeding. Indian mothers infected with HIV routinely breastfeed and have transmission rates as high as 48%.

Perinatal transmission rates are relatively low in Europe and high in Africa, independent of treatment. Untreated women infect 13% and 40% of children in Europe and Africa, respectively. The rate of postnatal transmission in Africa and other developing countries is elevated because of the need to breastfeed.

HIV-1 is the most common cause of HIV infection in the Americas, Europe, Asia, and Africa. HIV type 2 (HIV-2) has caused epidemics in West Africa, though this virus is also found in European countries. HIV-1 subtypes differ by geographic region. Non-B subtypes are particularly prevalent in Africa and in Asia. The high transmission rate from Africa to Europe has increased the diversity of subtypes in Europe.

Mortality/Morbidity

The natural progression of vertically acquired HIV infection appears to have a trimodal distribution. Approximately 15% of children have rapidly progressive disease, and the remainder has either a chronic progressive course or an infection pattern typical of that observed in adults. Mean survival is about 10 years. In resource-poor nations, the progression to death accelerates. In some instances, close to 45-90% of HIV-infected children died by the age of 3 years. However, among children and adolescents, the start of combination therapy including protease inhibitors reduces the risk of death by an estimated 67%. Also, host genetics play an important role in HIV-1–related disease progression and neurologic impairment

The progression and prognosis of children with HIV infection is represented by using CDC classification system. This classification system is outlined in Prognosi s.

Race

Black and Hispanic children are disproportionately affected. As of 2002, HIV infection was the 7th and 10th leading cause of death in black children and in Hispanic teens, respectively.¹ Approximately 62% of children with AIDS are black.

Sex

Women of childbearing age are one of the fastest growing groups with AIDS; 20% of AIDS cases in adults occur in this group.

Age

Vertical HIV infection occurs during 1 of the following 3 periods:

• Period 1, before birth: The fetus can be hematologically infected by means of transmission across the placenta or across the amniotic membranes, especially if the membranes are inflamed or infected.
• Period 2, delivery: Most vertical infections occur during delivery, and many factors affect the risk of infection during this period (see Deterrence/Prevention). In general, the longer and the greater amount of contact the neonate has with infected maternal blood and cervicovaginal secretions, the greater the risk of vertical transmission. Premature and low-birthweight neonates appear to have an increased risk of infection during delivery because of their reduced skin barrier and immunologic defenses.
• Period 3, after birth: Postnatal vertical transmission occurs with the ingestion of HIV in the breast milk.

The age of presentation can be highly variable in a high-risk child who was previously unidentified. Children can be asymptomatic for many years, and the appearance of an opportunistic infection in a 10-year-old child or in an adolescent in whom AIDS is subsequently diagnosed is not rare. Children who acquire HIV by means of nonvertical transmission may have an illness during the acute phase of the retroviral syndrome, or they may present many years later with opportunistic or recurrent infections.

Before 1985, contaminated blood products were the vehicles for transmission in many cases. Now, nonvertically transmitted HIV usually occurs by means of sexual contact and IV drug use.

The CDC estimates that 50% of all new HIV infections in the United States occur among individuals aged 13-24 years. This is an important statistic that influences the mortality rates in young adults. For example, HIV is the 5th leading cause of death among black women aged 20-24 years, and it is the principal cause of mortality in black women aged 25-34 years.

Clinical

History

• Human immunodeficiency virus (HIV) infection
  • Immunodeficiency should be suspected in individuals with recurrent bacterial infections (especially invasive infections, eg, bacteremia, meningitis, and pneumonia) and in those with unusual infections, such as those caused by the Mycobacterium avium-intracellulare complex (MAC).
  • Children with HIV infection often present with the common bacterial infections of childhood (eg, otitis media, sinusitis, pneumonia). These can be more frequent and more severe than similar infections in immunologically healthy children.
  • Recurrent fungal infections, such as candidiasis (thrush), that do not respond to standard antifungal agents suggest lymphocytic dysfunction.
  • Recurrent or unusually severe viral infections, such as recurrent or disseminated herpes simplex or zoster infection or cytomegalovirus (CMV) retinitis, are seen with moderate-to-severe cellular immune deficiency.
• Growth
  • Growth failure, failure to thrive, or wasting in the child may indicate HIV infection if other common metabolic and endocrine disorders do not appear to be the etiologies.
  • Growth failure, failure to thrive, or wasting in the patient with HIV infection may signify disease progression or underlying malnutrition.
• Development
  • Failure to attain typical milestones suggests a developmental delay. Such delays, particularly impairment in the development of expressive language, may indicate HIV encephalopathy.
  • The loss of previously attained milestones may signify a CNS insult due to progressive HIV encephalopathy or opportunistic infection.
  • In older children, behavioral abnormalities (eg, loss of concentration and memory) may indicate HIV encephalopathy.

Physical

Few physical findings are specific to HIV infection, and many physical findings are caused by opportunistic infections. Lymphadenopathy, hepatomegaly, and splenomegaly are fairly common in HIV infection. Other findings may include those discussed below.

• Anthropometric findings
  • Monitoring the patient's growth is one of the most important parts of the physical examination. Anthropometric measurements should be obtained at each visit.
  • Delayed growth in the head circumference is correlated with the development of underlying encephalopathy. However, normal head growth does not help in ruling out encephalopathy, and many patients with a normal head circumference may have radiographic or psychometric findings consistent with encephalopathy.
  • Fat redistribution syndrome in association with lipid abnormalities and insulin resistance is being described in HIV-infected children and adults. Presentations vary (eg, central adiposity vs peripheral fat wasting) and depend on factors such as race and age. Body habitus is altered because of lipoatrophy, lipohypertrophy, or both. Diverse diagnostic criteria have been used. Anthropometric measurements, such as skin-fold thickness and the waist-to-hip ratio, are useful to monitor the progression of changes. Technically sophisticated tools include bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DEXA), CT, and MRI.
• Head, eyes, ears, nose, and throat (HEENT) findings
  • Parotid enlargement is observed in 30% of children with category C disease and in 15% of children with disease in other categories.
  • Tonsillar hypertrophy may be observed.
  • Aphthous ulcers may be observed.
  • Thrush in the oral cavity and posterior pharynx is observed in approximately 30% of HIV-infect children. In children with AIDS, the prevalence of thrush is correlated with a low CD4⁺ count. Thrush in the posterior pharynx may signify candidal esophagitis, especially in patients with feeding difficulties or retrosternal pain.
  • CMV retinitis occurs in 3.4% of children with CD4⁺ counts of less than 50 X 10⁹/L.
• Cardiac findings
  • Cardiomyopathy may be present.
  • Congestive heart failure may be present.
• Pulmonary findings
  • Lung examination is important, and good documentation of findings is required at each visit.
  • Chronic lung disease may produce baseline findings of crackles and decreased regional breath sounds.
  • Changes in the lung findings are important to note because pneumonia is common in children with HIV infection. Pneumonia may not be obvious during the examination, and many children have few symptoms. For example, Mycoplasma infection may not cause a high temperature, and Pneumocystis jiroveci infection may cause only tachypnea, fever, and hypoxemia.
  • Changing findings at lung examination may also signify worsening of chronic lung disease, lymphoid interstitial pneumonitis, or tuberculosis (TB).
• Abdominal findings
  • Hepatomegaly is observed in 70% and 45% of children with and children without AIDS, respectively.
  • Splenomegaly is observed in about 35% of children with HIV infection.
• Lymphatic findings
  • Generalized cervical, axillary, or inguinal lymphadenopathy is common and may be the first sign of initial infection during the asymptomatic phase of the disease. Generalized lymphadenopathy may not be present with well-controlled disease or end-stage AIDS. New shotty nodes may indicate that the disease has again progressed and that treatment failure has occurred.
  • A single large node may indicate lymphoma, and it may need to be examined with biopsy.
• Neurologic findings
  • Motor delay, hypotonia, hypertonia, and/or pyramidal-tract signs may indicate progressive HIV encephalopathy or opportunistic infection of the CNS.
  • Spastic diplegia and oral motor dysfunction are early signs of encephalopathy.
  • Acquired microcephaly with accompanying cerebral atrophy is a poor prognostic sign.
  • Subacute combined degeneration of the spinal cord with higher cortical dysfunction occurs in vitamin B-12 deficiency.
  • Ischemic and hemorrhagic strokes can occur in children with AIDS, but they seem to be related to infection or other mechanisms other than hypercoagulable states, as in the adult HIV-infected population.
• Skin findings
  • HIV dermatitis causes an erythematous papular rash and is observed in about 25% of children with HIV infection.
  • Vesicular lesions in a unilateral dermatomal distribution or in the oral, genital, or anal area may represent reactivation of herpes zoster.
  • Erythematous candidal dermatitis that does not respond to standard therapy may be present.
  • Bleeding or bruising of the mucous membranes and skin may be observed in children with HIV and immune thrombocytopenic purpura, although this is uncommon.
• Extremity findings
  • Digital clubbing may be observed as a result of chronic lung disease.
  • Nonpitting edema may result from hypoalbuminemia caused by HIV nephropathy or malnutrition.
  • Pitting edema may develop as a result of congestive heart failure.

Causes

• Infection is due to HIV, a complex member of the Lentivirus genus of the Retroviridae family.
• HIV-1 is the most common cause of HIV infection in the Americas, in Europe, in Asia, and in Africa. HIV-2 has caused epidemics in West Africa, although this virus is also found in European countries. HIV-2 disease progresses more slowly than HIV-1 disease, and HIV-2 is less transmissible than HIV-1.
• HIV-1 subtypes differ by geographic region. HIV-1 subtype B is predominant in the United States. Non-B subtypes are particularly prevalent in Africa and Asia. The high transmission rate from Africa to Europe has increased the diversity of subtypes in Europe. Non-B subtype HIV-1 infections are increasing in the United States.

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