The term “AIDS dysmorphic syndrome” or “HIV embryopathy” has been used by some researchers to describe specific facial malformations (i.e., craniofacial dysmorphism), an unusually small head, and growth deficiency in some infants infected with HIV.* Such craniofacial abnormalities have included a prominent, boxlike forehead, large, wide eyes; a flattened nasal bridge, and an unusually pronounced philtrum, which is the vertical groove in the center of the upper lip.
However, many investigators have since questioned the significance of these observations. Such researchers indicate that there is a lack of evidence for characteristic craniofacial malformations in infants who acquired HIV infection from their mother before, during, or shortly after birth (i.e., perinatally).
*HIV is the abbreviation for the human immunodeficiency virus, a retrovirus that infects certain white blood cells called helper T cells (CD4+ cells). HIV infection leads to progressive deterioration of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS).
Causes
Most new cases of HIV infection in young children (pediatric HIV infection) are caused by transmission from the mother during pregnancy, labor, and delivery, or breastfeeding (perinatal transmission). Estimates suggest that the transmission rate from untreated HIV-positive mothers in the United States is approximately 12 to 30 percent. (For further information, please see the “Standard Therapies” section of this report below.) Women with HIV infection are most often infected through heterosexual relations with an infected partner or injection drug use.
Symptoms
Some researchers have reported particular craniofacial abnormalities, described as “AIDS dysmorphic syndrome” or “HIV embryopathy”, in some infants who acquired HIV infection from their mother (perinatally). Such features have included a small head circumference (microcephaly); a prominent, boxlike forehead; a flattened nasal bridge and shortened nose; and/or an unusually pronounced vertical groove (philtrum) in the center of the upper lip. Various eye abnormalities have also been reported, such as unusually prominent and/or widely set eyes (ocular hypertelorism); slanting (obliquity) of the eyes; long eyelid folds (palpebral fissures); and/or an unusual bluish tint of the whites of the eyes (blue sclerae). Affected infants and children also typically had growth retardation, resulting in low weight and height as compared to others of the same age and sex. In some cases, growth failure began during fetal development (intrauterine growth retardation). Such features have varied in range and severity from case to case and have been noted before the development of symptoms associated with impaired functioning of the immune system (immunodeficiency).
However, as noted above, investigators have since cited a lack of evidence for characteristic craniofacial abnormalities in infants with perinatal HIV infection. Rather, according to such researchers, evidence suggests that there is no significant difference in the incidence of such features in affected children compared with those in the general population. In addition, although a significant number may have microcephaly and growth failure after birth, such abnormalities could be associated with chronic illnesses and progressive neurologic dysfunction (see below) due to HIV infection. Investigators also note that the observed features in infants with perinatal HIV infection must be differentiated from findings that may be due to exposure to alcohol, certain drugs, or other factors during pregnancy.
Symptoms of immunodeficiency due to perinatal HIV infection may become apparent during the first or second year of life or later during childhood. Common manifestations may include lung inflammation (lymphocytic interstitial pneumonitis); recurring bacterial infections; chronic fungal infection of the mouth (oral candidiasis); abnormal enlargement of the liver and spleen (hepatosplenomegaly); generalized swelling of lymph nodes (lymphadenopathy); swelling of certain salivary glands; rashes; persistent fever; chronic diarrhea; and severe weight loss (wasting). In addition, affected infants and children may develop chronic or recurrent infections with certain viruses, fungi, or other unusual opportunistic microorganisms. The term “opportunistic infections” refers to infections caused by microorganisms that usually do not cause disease in healthy individuals or to widespread (systemic) infection by microorganisms that typically cause only localized, mild infection. For example, affected infants and children may be prone to developing severe lung inflammation (pneumonia) due to infection with a microorganism known as Pneumocystis carinii, which may result in potentially life-threatening complications. Although uncommon, there may also be an increased risk of developing particular malignancies, such as certain cancers of the lymphatic system (e.g., non-Hodgkins B-cell lymphomas, brain lymphomas).
As noted above, many affected infants and children may also develop progressive neurologic dysfunction, which may include delays in or loss of previously acquired developmental milestones; intellectual deterioration; microcephaly; and motor dysfunction. Various additional findings may also be present, including inflammation of the liver (hepatitis) and impaired functioning of the kidneys (renal failure) and the heart (heart failure).
Diagnosis
Perinatal HIV infection is considered in infants of mothers known to be HIV-positive and/or in infants and children who have certain characteristic symptoms of HIV infection or immune system abnormalities. Infants who are born to mothers with HIV have antibodies against the virus in the bloodstream at birth (passively acquired maternal antibodies). In infants and children who are not infected with HIV, these passive antibodies eventually disappear, usually between six to 12 months, however, in some cases, they may be detectable for up to 18 months. Therefore, testing that detects the presence of HIV antibodies in the blood (serum antibody tests, e.g., enzyme immunoassay and confirmatory Western blot) in a child 18 months or older usually indicates infection; however, such testing is not conclusive in children younger than 18 months. In these children, HIV infection may be confirmed through the repeated use of various specialized viral detection laboratory tests (e.g., HIV viral cultures, a DNA-amplification and copying method known as polymerase chain reaction [PCR]). Additional laboratory tests may also be conducted to assess immune functioning to assist in diagnosis and to monitor disease progression and its treatment. Testing may include monitoring of helper T cell numbers (CD4+ cells), the ratio of helper T cells to certain other white blood cells (CD8+ cells), complete blood counts, and blood platelet levels.
Benign lymphadenopathy biopsies of HIV patients have shown one of the following morphological patterns:
- Florid follicular hyperplasia
- Mixed follicular hyperplasia and follicular involution
- Follicular involution
- Lymphocyte depletion
These histological features relate to the clinical stage of the disease with CD4 counts.[rx]
History and Physical
A large number of patients may only have an asymptomatic infection after exposure. The usual time from exposure to onset of symptoms is 2 to 4 weeks, although, in some cases, it can be as long as 10 months. A constellation of symptoms, known as an acute retroviral syndrome, may appear acutely. Although none of these symptoms are specific to HIV, their presence of increased severity and duration is an indication of poor prognosis. These symptoms, in the order of decreasing frequency, are listed below:
- Fatigue
- Muscle pain
- Skin rash
- Headache
- Sore throat
- Swollen lymph nodes
- Joint pain
- Night sweats
- Diarrhea[rx]
Chronic HIV infection can be characterized either without AIDS or with AIDS and can progress to advanced HIV infection:
- Chronic HIV infection without AIDS:
- Thrush
- Vaginal candidiasis
- Oral hairy leukoplakia
- Herpes zoster
- Peripheral neuropathy
- Bacillary angiomatosis
- Cervical dysplasia
- Cervical carcinoma in situ
- Constitutional symptoms
- Idiopathic thrombocytopenic purpura
- Chronic HIV infection with AIDS: AIDS is defined as a CD4 cell count <200 cells/microL or the presence of any AIDS-defining condition regardless of the CD4 cell count. AIDS-defining conditions relate to those opportunistic illnesses and malignancies that occur more frequently or more severely as a result of immunosuppression. These are listed below:
- Multiple or recurrent bacterial infections
- Recurrent pneumonia
- Candidiasis
- Cervical cancer, invasive
- Coccidioidomycosis
- Cryptococcosis, extrapulmonary
- Cryptosporidiosis, chronic intestinal
- Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month
- Cytomegalovirus retinitis (with loss of vision)
- HIV related encephalopathy
- Herpes simplex: chronic ulcers
- Histoplasmosis, disseminated or extrapulmonary
- Isosporiasis, chronic intestinal
- Kaposi sarcoma
- Lymphoma (Burkitt, immunoblastic or primary brain)
- Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
- Mycobacterium tuberculosis of any site
- Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
- Pneumocystis jirovecii
- Progressive multifocal leukoencephalopathy
- Advanced HIV infection is defined as a CD4 cell count <50 cells/microL
Lab Test
HIV infection can remain undetected for years. However, they are several tests to diagnose it:[rx][rx]
- Fourth-generation assay: Detect specific antibodies and P24 HIV antigens
- Rapid test: Use blood or saliva to detect an HIV infection within hours
- Polymerase-chain-reaction: Can be a diagnostic or a confirmative test for HIV infection and can provide information about the viral load
When there is a possibility of acute or early HIV infection, the most sensitive screening immunoassay available (ideally, a combination antigen/antibody immunoassay) in addition to an HIV virologic (viral load) test is performed. RT-PCR-based viral load test is favored. A positive HIV virologic test generally indicates HIV infection.
Detectable viremia does not develop until approximately 10 to 15 days after infection, and even the most sensitive immunoassays do not give a positive result until five days after that. Therefore, initial negative immunoassay and virologic tests can be misleading, and if the clinical suspicion of recent HIV exposure is high, repeat testing is done one to two weeks later.
Treatment
Disease management and treatment may require the coordinated efforts of a team of medical professionals, including obstetricians, pediatricians, specialists in HIV infection, and additional health care professionals.
If pregnant women are infected with HIV, certain preventive measures may help to decrease the rate of transmission to their children. Such measures may include administration of the antiretroviral drug zidovudine (ZDV) by mouth (orally) during the second and third trimesters of pregnancy; intravenously during labor and delivery; and orally to the newborn during the first six weeks of life. Research has shown that, for selected HIV-infected pregnant women, this regimen may decrease the rate of perinatal HIV transmission by more than two-thirds. (ZDV is a nucleoside reverse transcriptase inhibitor.)
HIV-infected women may have already been taking or may be offered standard antiretroviral combination therapy that is currently recommended for non-pregnant adults (two nucleoside reverse transcriptase inhibitors and a protease inhibitor). Such therapy may be offered both to improve the mother’s health and to potentially further reduce the risk of HIV transmission. Decisions concerning the use and choice of such medications during pregnancy should consider the potential benefits and risks to the mother and her child. However, as noted above, evidence indicates that therapy with the antiretroviral agent ZDV should be included to help prevent perinatal HIV transmission.
Some research also shows that elective delivery by cesarean section may reduce the risk of HIV transmission to the newborn. However, the potential risks and benefits of the cesarean section must be considered based on the specifics of each case. In addition, in the United States, HIV-infected mothers are advised not to breastfeed, since clean water and infant formulas are readily available.
As noted above, the treatment of HIV-infected infants and children may require the coordinated efforts of a multidisciplinary team of medical professionals, including specialists in pediatric HIV infection. Recommended disease management may include combination therapy with various antiretroviral agents, such as two nucleoside reverse transcriptase inhibitors (e.g., ZDV with didanosine or lamivudine), possibly in combination with a third medication belonging to the class of drugs known as protease inhibitors. The specific combination therapies recommended may depend upon the child’s age, symptoms, amount of virus in the blood (viral load), ability or inability to tolerate certain medications, possible drug interactions, and/or other factors. Children should be regularly monitored for evidence of disease progression, to assess the effectiveness of therapy, and to make any necessary therapy adjustments.
Disease management may also include the administration of certain antibiotics to help prevent and/or aggressively treat particular infections (e.g., Pneumocystis carinii). In addition, certain corticosteroids may be prescribed. Intravenous immune globulin may also be recommended to help boost the ability of the immune system to fight certain infections. In addition, regular tuberculosis screening is advised.
Most routine childhood vaccinations may be provided to most children with HIV infection. However, generally, live bacterial or viral vaccinations are not used (although there may be some exceptions, such as the measles-mumps-rubella vaccine). In addition, when affected children are exposed to vaccine-preventable infectious diseases, immune globulin may sometimes be indicated.
Pediatricians may also provide parents of HIV-infected children with certain guidelines to help reduce the risk of potential infections. These may include avoiding raw or undercooked meat; understanding the importance of thorough handwashing; avoiding swimming in or drinking lake or river water; avoiding contact with farm animals, and understanding the potential risks of playing with pets.
Additional therapies are under evaluation for the treatment of HIV infection in children. Another treatment for affected infants and children is symptomatic and supportive.
or
Single Tablet Regimens
- Efavirenz/emtricitabine/tenofovir disoproxil is a tablet comprising 600-mg efavirenz, 200-mg emtricitabine, and 245-mg tenofovir disoproxil. It should be taken as a single pill once a day. It can cause sleep disturbances, tiredness, dizziness, rash, nausea, vomiting, diarrhea, abnormal dreams, impaired concentration, headache, anxiety, depression, raised creatine kinase levels, skin darkening, low blood phosphate levels, and weakness, stomach pains, bloating, and flatulence.
- Rilpivirine/emtricitabine/tenofovir disoproxil is a tablet comprising 25-mg rilpivirine, 200-mg emtricitabine, and 245-mg tenofovir disoproxil. It should be taken as a single pill once a day. Side effects include nausea, vomiting, diarrhea, dizziness, insomnia, headache, fatigue, weakness, rash, stomach pains, flatulence, changes in kidney function, raised creatine kinase levels, low blood phosphate levels, skin darkening, mood changes, and depression.
- Rilpivirine/tenofovir alafenamide/emtricitabine is a tablet comprising 25-mg rilpivirine, 25-mg tenofovir alafenamide, and 200-mg emtricitabine. It should be taken as a single pill once a day. It can cause reduced white, and red blood cells and platelet count, raised lipids, tiredness, headache, dizziness, insomnia, depression, nausea, abdominal pain, vomiting, flatulence, liver enzymes, dry mouth, and raised amylase levels, and bilirubin.
- Elvitegravir /cobicistat/emtricitabine/tenofovir alafenamide is a tablet containing 150-mg elvitegravir, 150-mg cobicistat, 200-mg emtricitabine, and 10-mg tenofovir alafenamide. It should be taken as a single tablet once a day. Side effects of this regimen include nausea, abnormal dreams, diarrhea, vomiting, stomach pain, headache, dizziness, rash, and tiredness.
- Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil is a drug comprising 150-mg elvitegravir, 150-mg cobicistat, 200-mg emtricitabine, 245-mg tenofovir disoproxil. It should be taken as a single tablet once a day. It can cause nausea, headache, fatigue, diarrhea, dreams, dizziness, insomnia, rash, flatulence, and sleepiness.
- Dolutegravir/abacavir/lamivudine is an antiretroviral comprising 50-mg dolutegravir, 600-mg abacavir, and 300-mg lamivudine. It should be taken as a single tablet once a day. Side effects include insomnia, headache, diarrhea, stomach pain, drowsiness, dizziness, hair loss, nausea, fatigue, rash, itching, vomiting, depression, flatulence, muscle pain and discomfort, irritated or a runny nose, indigestion, and loss of appetite.
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
- Abacavir (300 mg), a tablet, should be taken twice a day or 600 mg once a day. Its side effects include nausea, fever, headache, vomiting, diarrhea, abdominal pain, tiredness, and loss of appetite.
- Emtricitabine (200 mg), a capsule, should be taken once a day. It can cause nausea, raised creatine kinase levels, diarrhea, headache, and skin darkening.
- Lamivudine 150 and 300 mg, a tablet of 150 mg should be taken twice a day or 300 mg once a day. The regimen can cause nausea, vomiting, diarrhea, abdominal pain, hair loss, fever, insomnia (difficulty sleeping), rash, tiredness, and joint pain.
- Zidovudine comes in 100- and 250-mg capsules. A capsule (250 mg) should be taken twice a day. Common side effects are nausea, fatigue, headache, weakness, muscle pain, vomiting, loss of appetite, and fever.
- Tenofovir disoproxil (245 mg) should be taken once a day. It can cause nausea, vomiting, diarrhea, low blood phosphate levels, flatulence, dizziness, weakness, rash, headache, stomach pains, and fatigue.
NRTI Fixed-Dose Combinations
- Abacavir/lamivudine: Tablet comprising 600-mg abacavir and 300mg lamivudine. It should be taken one tablet once a day. Its commonest side effects include nausea, vomiting, diarrhea, loss of appetite, hair loss, cough, fever, headache, stomach pains, tiredness, runny nose, insomnia (difficulty sleeping), muscle pain, rash, joint pain, and hypersensitivity reaction.
- Abacavir/lamivudine/zidovudine: Tablet comprising 300-mg abacavir, 150-mg lamivudine, and 300-mg zidovudine. One tablet twice a day should be taken. It can cause nausea, vomiting, diarrhea, fever, loss of appetite, hair loss, cough, headache, stomach pains, tiredness, runny nose, insomnia (difficulty sleeping), joint pain, rash, dizziness, muscle pain, and hypersensitivity reaction.
- Emtricitabine/tenofovir disoproxil: Tablet comprising 200-mg emtricitabine and 245-mg tenofovir disoproxil. One tablet, once a day, should be taken. It can cause nausea, diarrhea, vomiting, flatulence, dizziness, headache, raised creatine kinase levels, rashes, low blood phosphate levels, weakness, rash, skin darkening, stomach pains, and difficulty sleeping.
- Lamivudine/zidovudine: Tablet comprising 150-mg lamivudine and 300-mg zidovudine. It should be taken one tablet twice a day. Its significant side effects include nausea, vomiting, diarrhea, headache, insomnia (difficulty sleeping), cough, runny nose, stomach pains, hair loss, fever, rash, tiredness, joint pain, dizziness, muscle pain, and loss of appetite.
Integrase Inhibitors
- Dolutegravir 50-mg tablet: Take 50 mg once a day or 50 mg twice a day if taken with efavirenz, nevirapine, or tipranavir. It can cause nausea, diarrhea, headache, rash, itching, vomiting, dizziness, abnormal dreams, fatigue, flatulence, stomach pain or discomfort, insomnia, and an increase in liver and muscle enzymes.
- Raltegravir 400- mg tablet: It should be taken 400 mg twice a day. Its side effects include a headache, insomnia and rarely severe rash, hypersensitivity reaction, and extreme thirst.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
- Etravirine 100- and 200-mg tablets: It should be taken as a 200-mg tablet twice daily. The side effects are rash and peripheral neuropathy. Nevirapine 200-mg tablet is taken once a day for two weeks, then 200mg twice a day. It can cause liver toxicity, rash, nausea, headache, allergic reaction, fatigue, stomach pain, and diarrhea.
- The rilpivirine 25-mg tablet is taken once a day. Its significant side effects are insomnia, headache, rash, stomach pains, raised liver enzymes, depression, dizziness, and vomiting.
CCR5 Inhibitor
- Maraviroc 150- and 300-mg tablets: THis tablet should be taken at a dose of 300 mg twice a day. It can cause diarrhea, fatigue, headache, and rare liver disease.
Protease Inhibitors
- Atazanavir 150-, 200- and 300-mg capsules: The 300-mg formula also comes with 100-mg ritonavir and should be taken once a day. It can cause nausea, diarrhea, rash, stomachache, headache, insomnia, hyperbilirubinemia, lipodystrophy, vomiting, liver toxicity, and diabetes.
- Darunavir 600- and 800-mg tablet: It should be taken as an 800-mg tablet with 100-mg ritonavir once a day. Its common side effects include diarrhea, nausea, rash, stomach pain, headache, lipodystrophy, diabetes, and liver toxicity.
- Lopinavir /ritonavir tablet is comprised of 20-mg lopinavir and 50-mg ritonavir that is taken as 2 tablets twice a day or 4 pills once a day. It may cause lipodystrophy, raised liver enzymes, nausea, abdominal pain, weakness, vomiting, heartburn, headache, diarrhea, increased lipids, liver toxicity, and diabetes.
- Atazanavir /cobicistat tablet is comprised of 300-mg atazanavir and 150-mg cobicistat. It should be taken once a day. It can cause jaundice, hyperglycemia, dry mouth, headache, dizziness, vomiting, diarrhea, sleep problems, hyperbilirubinemia, rash, fatigue, and lipodystrophy.
Complications
A complication of HIV disease is its progression to acquired immunodeficiency syndrome (AIDS). The physician should suspect it once opportunistic infections and/or low CD4 count are present in an individual who is HIV positive.
AIDS occurs when lymphocyte count falls below a level (less than 200 cells per microliters) and is characterized by one or more of the following:[rx][rx]
- Tuberculosis (TB)
- Cytomegalovirus
- Candidiasis
- Cryptococcal meningitis
- Cryptosporidiosis
- Toxoplasmosis
- Kaposi sarcoma
- Lymphoma
- Neurological complications (AIDS dementia complex)
- Kidney disease
References
Aicardi Syndrome
