A majority of infants are usually asymptomatic until approximately 3 years of age, which is considered to be the median age for the appearance of symptoms [15]. Clinical criteria for children < 13 years of age with HIV infection somewhat differs from adult criteria and divides children into categories [6] [15]:

Category N: Asymptomatic
Children without any signs or symptoms considered to be the result of HIV infection or those who have only one of the conditions listed in category A.

Category A (mildly symptomatic) - Infants or children that present wth 2 or more of the following: dermatitis, hepatomegaly, splenomegaly, lymphadenopathy ( > 2 sites involved or bilateral involvement of one site), parotitis, recurrent or persistent upper respiratory tract infection, sinusitis, or otitis media.

Category B (moderately symptomatic) - The list of conditions included as defining criteria, in addition to category A symptoms, include:

• Oral candidiasis that persists for more than two months in a child of more than six months of age.
• Single episode of bacterial meningitis, pneumonia or sepsis.
• Recurrent or chronic diarrhea.
• Herpes simplex virus (HSV) infection (recurrent stomatitis, bronchitis, pneumonitis or esophagitis), toxoplasmosis or cytomegalovirus (CMV) infection before 1 month of age.
• Disseminated varicella infection.
• Hepatitis
• Nephropathy
• Persistent fever lasting more than one month
• Neutropenia (< 1,000/µL), thrombocytopenia (< 100,000/µL) or anemia (< 8 g/dL).
• Cardiomyopathy
• Leiomyosarcoma
• Lymphoid interstitial pneumonitis

Category C (severely symptomatic) - considered as the most severe stage of HIV infection and the prelude to AIDS, various life-threatening conditions fall under this category:

• Wasting syndrome - persistent weight loss of > 10%, downward crossing of two or more percentile lines on the weight-for-age chart in a child older than 1 year, accompanied by either chronic diarrhea or fever for 30 or more days.
• Recurrent septicemia, pneumonia, meningitis, osteomyelitis, arthritis, or other internal organ infections.
• Disseminated or extrapulmonary mycobacterium infection, either tuberculosis or non-tuberculous mycobacteria (NTM).
• Fungal infections - Pneumocystis jirovecii pneumonia (PCP), candidiasis (esophageal or pulmonary), cryptococcosis, histoplasmosis (extrapulmonary), cerebral toxoplasmosis and disseminated coccidiomycosis.
• Malignant diseases - Various forms of lymphoma (Burkitt's, immunoblastic, large-cell) and Kaposi's sarcoma.
• Severe CMV or HSV infection.
• Encephalopathic findings such as failure to thrive and impaired brain growth, as well as the presence of motor deficits (paresis, ataxia, gait disturbance or abnormal reflexes).
• Progressive multifocal leukoencephalopathy (PML).

• Splenomegaly

  […] infections, developmental delay X-linked lymphoproliferative syndrome X-linked SH2D1A (type 1) XIAP (type 2) Asymptomatic until onset of Epstein-Barr virus infection, then fulminant or fatal infectious mononucleosis with liver failure, B-cell lymphomas, splenomegaly [msdmanuals.com]

  Category A (mildly symptomatic) - Infants or children that present wth 2 or more of the following: dermatitis, hepatomegaly, splenomegaly, lymphadenopathy ( > 2 sites involved or bilateral involvement of one site), parotitis, recurrent or persistent upper [symptoma.com]

  Patients may develop lymphadenopathy and splenomegaly. If untreated, most children may die by the age of 2. [idoj.in]

• Fever

  At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. [ped-rheum.biomedcentral.com]

  However, in addition to AIDS as defined by the CDC, it is clear that there are several related syndromes which include individuals with chronic lymphadenopathy, fever, and weight loss (lymphadenopathy syndrome); other malignancies; and healthy homosexuals [pediatrics.aappublications.org]

  Urticaria-like (nonpruritic) rash is characteristic of Cryopyrin associated periodic fever syndrome (CAPS). Children with CAPS are usually symptomatic since early infancy with fever and rash. [idoj.in]

  Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea. [ebi.ac.uk]

  […] of 100.5°F (38°C) or higher A cough with shortness of breath Stomach pain Other new symptoms Go to the emergency room or call your local emergency number (such as 911) if you have a stiff neck and headache with the fever. [medlineplus.gov]

• Anemia

  The neonate had mild anemia but no other signs of congenital CMV infection. AB - A pregnant woman with AIDS developed cytomegalovirus (CMV) retinitis and pneumonitis, requiring intravenous ganciclovir. [experts.umn.edu]

  Various hormonal and metabolic disorders can also result in immune deficiency including anemia, hypothyroidism and hyperglycemia. Smoking, alcoholism and drug abuse also depress immune response. [en.wikipedia.org]

  Disorder Inheritance Genes Affected Clinical Findings Common variable immunodeficiency Variable BAFFR, CTLA4, ICOS, NKFKB2, PIK3CD, STAT3, TACI Recurrent sinopulmonary infections, autoimmune disorders (eg, immune thrombocytopenia, autoimmune hemolytic anemia [msdmanuals.com]

  They both can present with a combination of symptoms including fevers, rashes, weight loss, joint pain, anemia, leukopenia, proteinuria, vasculitis, etc. [ped-rheum.biomedcentral.com]

  Provides clues as to the underlying disease, e.g., microcytes may indicate iron deficiency, spherocytes may indicate congenital or acquired immune anemia, and target cells may indicate liver disease or hemoglobinopathy. [glosbe.com]

• Recurrent Infection

  Recurrent infection and malnutrition are major problems in the clinical management of child AIDS patients. [ncbi.nlm.nih.gov]

  Key points • Congenital HIV infection is maternal-to-child transmission of HIV-1. • Prevalence is 1% to 2% in the United States with initiation of antiretroviral treatment of mothers during pregnancy. • The disease can be mild to severe, including recurrent [medlink.com]

  SCID patients are usually diagnosed in the first year of life with symptoms such as recurrent infections and failure to thrive. [immunology.org]

• Candidiasis

  Meets the case definition for HIV infection; AND Diagnosed with one or more of the following indicator diseases for adult and pediatric cases: - Bacterial pneumonia, recurrent [1] - Candidiasis of bronchi, trachea or lungs - Candidiasis of esophagus [ [bccdc.ca]

  Fungal infections - Pneumocystis jirovecii pneumonia (PCP), candidiasis (esophageal or pulmonary), cryptococcosis, histoplasmosis (extrapulmonary), cerebral toxoplasmosis and disseminated coccidiomycosis. [symptoma.com]

  Esophageal candidiasis was diagnosed in 2 patients by the presence of pseudohyphae and budding yeast forms [Figure 1]d. [ijpmonline.org]

  Stage 3: Loss of weight (>10% of body weight); chronic diarrhoea(> 1 month); prolonged fever; oral candidiasis; oral hairy leukoplakia; pulmonary tuberculosis; severe bacterial infections and vulvovaginal candidiasis. [slideshare.net]

• Weight Loss

  However, in addition to AIDS as defined by the CDC, it is clear that there are several related syndromes which include individuals with chronic lymphadenopathy, fever, and weight loss (lymphadenopathy syndrome); other malignancies; and healthy homosexuals [pediatrics.aappublications.org]

  Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea. [ebi.ac.uk]

  Symptoms vary child-to-child depending on age, but may include: lymph nodes that remain enlarged for more than three months lack of energy weight loss frequent and long-lasting fevers and sweats persistent or frequent yeast infections (oral or vaginal [childrenshospital.org]

  They both can present with a combination of symptoms including fevers, rashes, weight loss, joint pain, anemia, leukopenia, proteinuria, vasculitis, etc. [ped-rheum.biomedcentral.com]

• Cough

  CASE HISTORY • Part 1 A 23-year-old woman presents with recurrent episodes of sinusitis, a well-documented pneumococcal pneumonia at age 17, and a chronic productive cough for over a year; the latter has not responded to several courses of antibiotics [hemonc.mhmedical.com]

  She was then brought into her pediatrician's office complaining of a nonproductive cough for three months. She described shortness of breath, left pleuritic chest pain, fevers to 101°F, chills, and night sweats for one week. [ped-rheum.biomedcentral.com]

  […] disorders may include: Frequent or ongoing illness Increased risk of certain cancers or tumors Increased risk of infection Call your provider right away if you are on chemotherapy or corticosteroids and you develop: A fever of 100.5°F (38°C) or higher A cough [medlineplus.gov]

  Adult Health--Immune (HIV/AIDs questions) A client with acquired immunodeficiency syndrome (AIDS) is admitted to the hospital for chills, fever, nonproductive cough, and pleuritic chest pain. [flashcardbook.com]

  HIV cannot be transmitted by: Casual contact Food, air, water Vectors-Coughing, sneezing, spitting. Shaking hands, touching, dry kissing or hugging. Swimming pools, toilets, etc. 40. [slideshare.net]

• Diarrhea

  RESULTS: 6 of the 9 children had diarrhea and failure to thrive all within the first 9 mo. of life. [nature.com]

  (diarrhea that may come and go) oral thrush (a fungal infection in the mouth that is characterized by white patches on the cheeks and tongue) constant or recurring ear infections swelling of the lung tissue hepatitis chicken pox that may include the [childrenshospital.org]

  […] leukemia Immune-complex diseases, like viral hepatitis Multiple myeloma (cancer of the plasma cells) While each immunodeficiency condition can have varying symptoms, some of the more common symptoms include: Pink eye (conjunctivitis) Sinus infections Colds Diarrhea [umiamihealth.org]

  Hypoplasia of lymphoid tissue Absent or low B cells Normal T-cell count Low immunoglobulins of all classes Selective IgA deficiency Unknown The most common primary immunodeficiency Often asymptomatic May manifest with respiratory infections, and/or chronic diarrhea [amboss.com]

  Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea. [ebi.ac.uk]

• Failure to Thrive

  RESULTS: 6 of the 9 children had diarrhea and failure to thrive all within the first 9 mo. of life. [nature.com]

  These digestive problems can lead to failure to gain weight and grow at the expected rate (failure to thrive) and malnutrition. Most affected children are better able to tolerate sucrose and maltose as they get older. [ghr.nlm.nih.gov]

  […] to thrive Low IgG, IgA, and IgE Normal or increased IgM Lymph node biopsy: absent germinal centers Ataxia telangiectasia Autosomal recessive inheritance Defective ATM gene → failure to repair dsDNA breaks → cell cycle arrest Onset: early childhood Classic [amboss.com]

  Other frequent conditions are chronic diarrhea (often, but not always due to infection), failure to grow and develop normally (also called failure to thrive), and recurrence of persistent thrush, a fungal infection in the mouth. [childrenscolorado.org]

  Failure to thrive and delayed or incomplete recovery from illness. 7. [slideshare.net]

• Chronic Diarrhea

  Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea. [ebi.ac.uk]

  chronic candidiasis (thrush), viral and protozoal infections Failure to thrive Chronic diarrhea Lymph nodes and tonsils may be absent Diagnosis Quantitative PCR: ↓ T-cell receptor excision circles (TRECs) Flow cytometry: absent T cells CXR: absent thymic [amboss.com]

  diarrhea or fever for 30 or more days. [symptoma.com]

  Other frequent conditions are chronic diarrhea (often, but not always due to infection), failure to grow and develop normally (also called failure to thrive), and recurrence of persistent thrush, a fungal infection in the mouth. [childrenscolorado.org]

• Oral Ulcers

  Resistant thrush, oral ulcers and conjunctivitis. Diarrhoea and malabsorption. Failure to thrive and delayed or incomplete recovery from illness. 7. [slideshare.net]

  ulcerations Absolute neutropenia, relative monocytosis Bone marrow aspirate: normal or decreased cellularity; arrest of myeloid lineage Complement disorders Immunodeficiency Etiology Clinical features Diagnostic findings C1 esterase inhibitor deficiency [amboss.com]

  […] any pus exudate and oral ulcers [Figure 5]. [idoj.in]

• Aphthous Stomatitis

  Patients also have recurrent viral, bacterial infections, fungal (disseminated coccidioidomycosis and histoplasmosis), mycobacterial infections, aphthous stomatitis, and autoimmune manifestations.[25],[26] Figure 3: (a-f): Hyperkeratotic lesions involving [idoj.in]

• Hepatosplenomegaly

  Almost all young children with AIDS have hepatosplenomegaly, interstitial pneumonitis, and poor growth. The average age of 36 US child AIDS victims studied in detail was 5 months at presentation with findings suggestive of severe immunodeficiency. [ncbi.nlm.nih.gov]

  (although still rare) phagocytic cell defects are Phagocytic Cell Defects Disorder Inheritance Genes Affected Clinical Findings Chédiak-Higashi syndrome Autosomal recessive LYST (CHS1) Oculocutaneous albinism, recurrent infections, fever, jaundice, hepatosplenomegaly [msdmanuals.com]

  The clinical manifestations were failure to thrive; 9 children, persistent gastroenteritis; 8, recurrent fever; 5, bacterial infections; 5, hepatosplenomegaly; 5, candidiasis; 1, scabies; 1, skin rash; 2, tuberculous (TB) meningitis; 1 and paraplegia; [ijpmonline.org]

  After discharge in April 1981, the infant appeared well, although hepatosplenomegaly was noted at age 4 months. At 7 months, he was hospitalized for treatment of severe otitis media. [cdc.gov]

  […] infants and children encompasses a broad classification of diseases and signs that may appear and classifies patients into categories: Category N: asymptomatic patients or with only one condition listed under Category A; Category A (examples include hepatosplenomegaly [symptoma.com]

• Hepatomegaly

  She has palpable, slightly enlarged, non-tender cervical lymph nodes and a palpable spleen without hepatomegaly. [hemonc.mhmedical.com]

  Category A (mildly symptomatic) - Infants or children that present wth 2 or more of the following: dermatitis, hepatomegaly, splenomegaly, lymphadenopathy ( > 2 sites involved or bilateral involvement of one site), parotitis, recurrent or persistent upper [symptoma.com]

• Arthritis

  Arthritis Rheum. 1991, 34: 372-3. 10.1002/art.1780340318. 8. [ped-rheum.biomedcentral.com]

  Immunosuppression is one form of secondary immunodeficiency performed to prevent the body from rejecting an organ transplant, treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases, such as rheumatoid arthritis [bio.libretexts.org]

  […] school-age children with congenital human immunodeficiency virus infection: a pilot study. 61 Havens JF...Ehrhardt AA 7520454 1994 19 A comparison of immunoglobulin G-containing high-molecular-weight complexes isolated from children with juvenile rheumatoid arthritis [malacards.org]

  Arthritis Res Ther 2012;14:228. 16. Minegishi Y, Karasuyama H. Hyperimmunoglobulin E syndrome and tyrosine kinase 2 deficiency. Curr Opin Allergy Clin Immunol 2007;7:506-9. 17. [idoj.in]

  In addition to chronic and/or recurrent infections many autoimmune diseases including arthritis, autoimmune hemolytic anemia, scleroderma and type 1 diabetes are also seen in X-linked agammaglobulinemia (XLA). [en.wikipedia.org]

• Dermatitis

  […] cell histiocytosis in some patients Hyper-IgE syndrome Autosomal dominant or recessive STAT3 (dominant) TYK2, DOCK8 (recessive) Sinopulmonary infections; staphylococcal abscesses of skin, lungs, joints, and viscera; pulmonary pneumatoceles; pruritic dermatitis [msdmanuals.com]

  Category A (mildly symptomatic) - Infants or children that present wth 2 or more of the following: dermatitis, hepatomegaly, splenomegaly, lymphadenopathy ( > 2 sites involved or bilateral involvement of one site), parotitis, recurrent or persistent upper [symptoma.com]

  […] human immunodeficiency virus infection and toxoplasmosis. 61 O'Donohoe JM...Holliman RE 1891297 1991 22 Selenium deficiency and cardiomyopathy in acquired immunodeficiency syndrome. 61 Kavanaugh-McHugh AL...Rowe S 1865554 1991 23 Cytomegalovirus diaper dermatitis [malacards.org]

  Most common presentation is eczematoid dermatitis and other less common manifestations include icthysiform or psoriasiform dermatitis, urticaria, and alopecia. [idoj.in]

• Eruptions

  This inflammation subsides temporarily till the time of eruption of permanent teeth and then this process continues leading to complete loss of all teeth. [idoj.in]

• Ataxia

  Specific conditions that must be excluded in children are primary immunodeficiency diseases (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia-telangiectasia, neutrophil function abnormality) and secondary immuno-deficiency associated with immunosuppressive [ncbi.nlm.nih.gov]

  Ataxia Telangiectasia (AT) Autosomal recessive progressive neurodegenerative childhood disorder associated with: Lack of coordination (cerebella ataxia) and dilation of facial blood vessels (telangiectasis) and slurred speech. [slideshare.net]

  […] telangiectasia See ataxia telangiectasia for details. [amboss.com]

  Combined Humoral and Cellular Immunity Deficiencies Disorder Inheritance Gene Affected Clinical Findings Ataxia-telangiectasia Autosomal recessive ATM Ataxia, telangiectasias, recurrent sinopulmonary infections, endocrine abnormalities (eg, gonadal dysgenesis [msdmanuals.com]

  Partial T-cell function occurs in conditions such as acquired immune deficiency syndrome (AIDS) and genetic conditions such as DiGeorge Syndrome, Ataxia Telangiectasia and Wiskott Aldrich syndrome. [columbiadoctors.org]

• Encephalopathy

  Demonstration of HIV—like particles in the characteristic giant cells in the brain has been instrumental in the recognition of HIV encephalopathy. Biopsy is helpful in the rapid diagnosis of opportunistic infections (OIs). [tandfonline.com]

  disseminated or extrapulmonary - Cryptococcosis, extrapulmonary - Cryptosporidiosis, chronic intestinal (> 1 month’s duration) - Cytomegalovirus disease (other than in liver, spleen or nodes) - Cytomegalovirus retinitis (with loss of vision) [1] - Encephalopathy [bccdc.ca]

  (I67.4) G93.3 바이러스성후의 피로 증후군(Postviral fatigue syndrome) 양성 근육통성 뇌척수염(Benign myalgic encephalomyelitis) G93.4 상세불명의 뇌병증(Encephalopathy, unspecified) 제외 : 알콜성 뇌병증(alcoholic encephalopathy)(G31.2) 독성 뇌병증(toxic encephalopathy)(G92) G93.5 뇌의 압박(Compression [dic.impact.pe.kr]

  Davis SL, Halstead CC, Levy N et al (1987) Acquired immune deficiency syndrome presenting as progressive infantile encephalopathy. J Pediatr 110: 884–888 PubMed Google Scholar 56. Price DB, Inglese CM, Jacob J et al (1988) Pediatric AIDS. [link.springer.com]

  HIV wasting syndrome; extrapulmonary tuberculosis; Pneumocystis carinii pneumoniae, Candidiasis of the oesophagus, trachea, bronchi or lungs; toxoplasmosis of the brain, cryptosporidiasis with mycobacteriosis; lymphoma; Kaposi’s sacoma (KS) and HIV encephalopathy [slideshare.net]

• Peripheral Neuropathy

  The peripheral system Neuropathies Neuronal neuropathies Neuronal neuropathies affect the axon or cell body of ventral-horn neurons or dorsal-root ganglion neurons. [britannica.com]

  Partial albinism Progressive peripheral neuropathy Peripheral smear: giant cytoplasmic granules in granulocytes and platelets Mild coagulation abnormalities Pancytopenia Myeloperoxidase deficiency Autosomal recessive inheritance Mutation in MPO gene → [amboss.com]

  Neurological manifestations include peripheral neuropathy and intellectual disability. Hair microscopy (just like GS) reveals pigment clumps but the clumps are relatively smaller compared to the hair shaft in GS. [idoj.in]

• Paresis

  Encephalopathic findings such as failure to thrive and impaired brain growth, as well as the presence of motor deficits (paresis, ataxia, gait disturbance or abnormal reflexes). Progressive multifocal leukoencephalopathy (PML). [symptoma.com]

  Bleeding into the pons causes paresis of all limbs and unconsciousness. Bleeding into the cerebellum produces typical signs of incoordination with headache and stiffness of the neck. [britannica.com]

• Abnormal Reflex

  Encephalopathic findings such as failure to thrive and impaired brain growth, as well as the presence of motor deficits (paresis, ataxia, gait disturbance or abnormal reflexes). Progressive multifocal leukoencephalopathy (PML). [symptoma.com]

If there is clinical suspicion of HIV in infants and children, based on signs and symptoms, then rapid confirmation of HIV as an underlying cause should be made. Detection of HIV antibodies through an enzyme-linked immunoassay (EIA) is the initial diagnostic test of choice, followed by detection of specific amino acid sequences through Western blot (WB) if the result comes back positive [4]. In most cases, only HIV-1 antibodies are tested because HIV-2 infection is rare in the developed world. But if clinical signs and symptoms are highly suggestive of HIV, and HIV-1 results are negative,then HIV-2 WB must be performed, especially in children whose mothers are from endemic regions [5]. Recently, a new generation of tests that include detection of the p24 antigen (which codes for the viral core) and IgG/IgM antibodies to p24 have been shown to be more sensitive than traditional testing. However, their use in general practice is yet to be solidified [4]. Once a confirmation of HIV infection is made, it is necessary to perform a quantitative detection of HIV genetic material (known as the viral load), a procedure performed by using PCR assays [4]. In general, detection of RNA in blood is performed, but in children, levels of HIV DNA are preferably measured (when possible) [4]. In addition to determining viral load, it is necessary to determine the CD4+ and total lymphocyte count, in order to categorize children according to immunologic findings [6]:

• In infants (< 1 year of age), no evidence of immune suppression is seen if ≥ 1500 lymphocytes/µL are present, with at least 34% being CD4+ T lymphocytes, while moderate suppression is diagnosed if between 750-1499 lymphocytes/µL, of which 26-33% are CD4+ T lymphocytes. Severe suppression is seen in in infants with < 750 lymphocytes/µL, with < 15% of CD4+ T cells.
• For children between years 1 and 5, ≥ 1000 lymphocytes/µL and ≥ 25 % of CD4+ T cells indicate no evidence of suppression, between 500-999 lymphocytes/µL and 15-24% of CD4+ T cells show evidence of moderate suppression, while severe suppression is diagnosed if < 500 lymphocytes/µL are detected with < 15% of CD4+ T cells.
• For children over 5 years, ≥ 500 lymphocytes/µL and 26% of CD4+ T cells, 200–499 lymphocytes/µL and 14–25% of CD4+ T cells and < 200 lymphocytes/µL with < 14% of CD4+ T cells determine little, moderate or severe suppression, respectively.

• Anergy

  Infectious diseases: HIV infection T-cell lymphopenia Decreased cellular immune response and anergy Defective antigen-specific antibody responses 출처 : Chinen, Javier, and William T. [incodom.kr]

  Anergy panel was non-reactive. Chest radiograph revealed extensive left lower lobe infiltrate. Chest CT Scan showed left lower lobe consolidation with no pleural effusion. [ped-rheum.biomedcentral.com]

• Lymphopenia

  […] syndromes: trisomy 21 Defective phagocytosis Defective chemotaxis Variable defects of antigen-specific immune responses Anti-inflammatory, immunomodulatory, and immunosuppressive drug therapy: corticosteroids, calcineurin inhibitors, cytotoxic agents Lymphopenia [incodom.kr]

  One of the early clues to an acquired immunodeficiency state is the development of absolute lymphopenia. At the same time, patients may manifest profound immune defects with normal or even elevated lymphocyte counts. [hemonc.mhmedical.com]

  RMRP Short-limbed dwarfism, common and opportunistic infections Combined immunodeficiency with inadequate but not absent T-cell function and normal or elevated immunoglobulins Autosomal recessive or X-linked NEMO Common and opportunistic infections, lymphopenia [msdmanuals.com]

  CMI defects: lymphopenia, CD4 - cell3. reduced Ab levels & low complement levels.4. functional asplenia.5. also, corticosteroids & immunosuppressivesincrease infection risks. 23. 6. [slideshare.net]

Although numerous challenges may be faced when initiating and maintaining treatment in young HIV-infected patients, including limitation of available drugs, toxicity of therapy, adherence to therapy and the development of resistance, it should be pointed out that therapy should be started as early as possible, with studies showing a 75% decreased mortality when treatment is started in early infancy [7]. The WHO has recently changed its guidelines and now recommend immediate initiation of therapy in children under 2 years of age regardless of the clinical stage or CD4+ cell count [16]. More importantly, disease progression is substantially reduced with early therapy, while a reduction in opportunistic infections, improved neurocognitive abilities and growth and a better quality of life,in general, have been observed [7]. This further strengthens the principle of immediate therapy to prevent MTCT. Of the many antiretroviral drugs, six are currently recommended for use in neonates - Lamivudine, emtricitabine and stavudine (RT inhibitors) nevirapine (NNRT inhibitors) and lopinavir-ritonavir, a protease inhibitor [8]. Most common side-effects of therapy are fat wasting, dyslipidemia, insulin resistance and suboptimal bone growth [16]. Management of non-AIDS-defining infections and diseases that lead to multiorgan failure must be considered, as studies have shown that they are a major cause of mortality in HIV infected children, rather than opportunistic infections and other AIDS-related conditions [17].

The progression of HIV disease in infants and children occurs at a much higher rate [7], but it is important to distinguish between the three modes of MTCT, as major differences in clinical progression and the pathogenesis of HIV infection exist [2]. The primary reason for a poorer prognosis of untreated neonates and infants compared to adults is the level of maturity of the immune system, which may be able to provide some form of protection when the infection is contracted during breastfeeding and adulthood, but intrapartum and in utero transmission carry a much worse prognosis, as the immune system is still not fully activated [2] [14].

Congenital AIDS is caused by HIV-1 and HIV-2 in a small subset of cases [5]. These are single-stranded enveloped RNA retroviruses that possess genes for three main enzymes that enable their life-long survival in CD4+ T-cells: reverse transcriptase (forms DNA from viral RNA), integrase (integrates viral genetic material into host DNA) and protease (cleaves necessary proteins and prepares the newly formed virion for release into the extracellular environment) [9]. Through a multi-step process that involves invasion of CD4+ T-cells and replication using the host machinery, the virus is able to persist. During pregnancy or delivery, MTCT may occur and result in congenital HIV infection which can progress to AIDS, if left untreated.

Current epidemiology studies estimate that 34 million people are living with HIV and that 10% comprise individuals younger than 15 years [10]. Of those 3.4 million children, 95% acquired the infection via MTCT, but a clear distinction between perinatal (or vertical) and behavioral (or horizontal) transmission is yet to be made [4] [11]. In the United States, approximately 4500 children < 15 years suffer from a perinatal HIV infection [4] [6]. Modes of vertical transmission include intrauterine, postnatally through breastfeeding or intrapartum, with estimated transmission rates of 5-10%, 5-15% and 10-20%, respectively [2]. In African countries, transmission rates are as high as 25%-45% in the absence of any forms of prevention [3], while other studies indicate that prolonged breastfeeding by HIV+ women who do not take therapy increases the transmission rate to 50% [4].

HIV viruses belong to a group of single-stranded RNA viruses that insert into the host DNA through a complex pathophysiologic mechanism. After transmission of the virus from an HIV+ individual, usually through sexual intercourse, the virus targets CD4+ T-helper cells, specifically the co-receptors CCR5 or CXCR4, initiating the first step in infection: fusion of the viral particle with the host cell [4]. This mechanism enables the virus to gain access to the intracellular environment where it can freely proceed to the next steps in its replication. Firstly, reverse transcriptase (RT) synthesizes DNA from viral RNA, which is then integrated into the cellular DNA through the activity of integrase. Finally, the host machinery transcribes viral DNA and produces viral RNA, as well as all the necessary viral particles (with the aid of a third viral enzyme, protease), eventually leading to release of virions into the extracellular environment [9]. In this way, HIV is integrated into the host DNA and is able to persist throughout life either in active or latent form [12], which is why life-long treatment is necessary [4]. MTCT of HIV infection may occur at three separate points [2]:

• In utero transmission - Despite the fact that the fetus is exposed to the maternal infection throughout the entire pregnancy, one of the possible reasons why only 5-10% of children are infected during this phase is because HIV replicates only in active CD4+ T-cells and they are practically non-existent in the fetus [2]. However, recent studies have shown that CD4+ T-cells harboring CCR5 coreceptors are found in the intestinal system of the fetus, which may be the primary mode of in utero MTCT [13]. Recent HIV-1 acquisition, high viral load and presence of Neisseria gonorrhoeae infection have shown to increase the risk of transmission during this period [2].
• Intrapartum transmission - Current theories hypothesize that transplacental transfer of the virus during delivery or exposure of the neonate to maternal secretions may be the cause of intrapartum infection, but viral shedding through the mucosal surfaces in this period are most likely the cause [8]. Scalp trauma of the neonate during delivery, vaginal candidiasis, prolonged rupture of membranes, chorioamnionitis,and a high maternal viral load predispose infants to a much higher risk for infection [2].
• Breastfeeding - Although the levels of HIV RNA are 100 times lower in breast milk than in the circulation, MTCT is possible through this mechanism, especially in the setting of mastitis and other inflammatory changes in the breast [2].

The single most important preventive strategy for congenital AIDS and mother-to-child transmission of HIV is early recognition and initiation of therapy [18] [19]. Zidovudine, an inhibitor of reverse transcriptase (RT), is recommended for administration in infants who were exposed to HIV within 6-12 hours of delivery, in doses of 4 mg/kg PO q12h for 6 weeks [4]. Nevirapine is given in addition to zidovudine when women did not use ART during their pregnancy and it is administered in three oral doses of 8-12 mg, depending on body weight at birth [4]. Other strategies include replacement feeding instead of breast milk for HIV+ positive mothers and elective cesarean section that will reduce the chance of contracting HIV during delivery [4]. Additionally, the recent identification of broadly neutralizing antibodies (bNAbs) as potential vaccine candidates is a major step toward HIV eradication, but further research is necessary [20].

Congenital acquired immune deficiency syndrome (AIDS) is a clinical entity characterized by mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), which causes life-long infection of CD4+T-helper cells [1]. It is estimated that approximately 3.4 million children are infected by HIV+ . In 95% of the cases, MTCT (also known as vertical transmission) is the cause, but the rate of transmission depends on the period when HIV is transferred to the child - intrauterine, intrapartum or through breastfeeding [2]. One of the factors that substantially increases the risk for congenital AIDS is non-adherence of women to antiretroviral therapy (ART), increasing the risk to 45-50% [3] [4]. Most cases occur due to HIV-1 infection, but in a small number of children, HIV-2 is responsible for congenital HIV+ infection, most commonly in West African countries - Nigeria, Sierra Leone, Gambia, Senegal and Guinea-Bissau [5]. HIV-2 is far less potent and infective, however, which is why reports show that perinatal transmission of HIV-2 is almost 6-fold lower compared to HIV-1 [5]. The pathogenesis model of congenital AIDS is complex and involves initial infection of the mother (through sexual intercourse, intravenous drug use or contaminated blood derivatives), viral replication and subsequent transfer of virions to the fetus [4]. Several theories exist why not all infants become infected with HIV, the most common theories being a relatively silent and immature immune system that renders HIV unable to replicate under such circumstances, but numerous conditions have been implied as possible determinants, including infections (gonorrhea, vaginal candidiasis and mastitis) prolonged rupture of membranes and other obstetric complications [4]. The clinical presentation of infants and children encompasses a broad classification of diseases and signs that may appear and classifies patients into categories: Category N: asymptomatic patients or with only one condition listed under Category A; Category A (examples include hepatosplenomegaly, parotitis, dermatitis and chronic respiratory infection); Category B (moderate signs including hepatitis, nephropathy, herpes simplex virus infections, neutropenia, etc.) and Category C, in which AIDS-defining illnesses such as Kaposi sarcoma, progressive multifocal leukoencephalopathy (PML), non-Hodgkin lymphoma and severe fungal and bacterial infections develop [6]. To make the diagnosis of congenital AIDS, it is imperative to perform a thorough physical examination and obtain a detailed patient history that includes the mother and associated risks for HIV. To confirm HIV infection, however, determination of HIV-antibodies in serum, followed by identification of specific amino-acid sequences through Western blot testing and determination of CD4+ T-cell count is necessary [1] [4] [6]. Initiation of treatment as soon as possible has recently been recommended (regardless of the CD4+ T-cell count and general condition of the child) and drugs such as zidovudine, nevirapine, lopinavir/ritonavir and stavudine have been shown to be safe for use in the neonatal population [7] [8]. MTCT of HIV and congenital AIDS may be prevented or even completely eliminated through wide-scale testing and early initiation of treatment in HIV-positive women, while avoidance of breast-feeding and introduction of cesarean sections during delivery are additional strategies to reduce the possibility of HIV transmission [4].

Congenital acquired immune deficiency syndrome (AIDS) is a condition that occurs after transmission of human immunodeficiency virus (HIV) from the mother to her child, which may occur during fetal life, labor or through breast feeding. HIV is a virus that infects CD4+ T-cells, one of the most important cells in the immune system and is able to replicate inside them using cellular organelles and its own specific enzymes. HIV is one of the most difficult viruses to treat because it is able to integrate its genetic material into our own, making viral eradication from the body practically impossible. Not all children are infected if their mothers are HIV-positive. Varying percentages have been observed depending on the mode of transmission, but the risk is highest if pregnant women are not on antiretroviral therapy (ART), leading to a 50% chance of transferring the infection to their child, primarily because much higher concentrations of the virus are present in untreated women. It is estimated that 34 million people are living with HIV and approximately 10% of total cases are children who developed an infection from their mother (also known as vertical transmission). Once HIV, which was previously contracted by the mother through sexual intercourse, intravenous drug use, or contact through contaminated blood or blood products (transfusions), reaches the fetus or neonate during birth, it is able to cause a more severe form of infection compared to adults, as the immune system of the child is still immature and has very few mechanisms of defense. For this reason, early initiation of treatment has been shown to be essential. Firstly, clinical signs and symptoms of HIV infection are well defined and should be recognized, followed by various tests such as detection of antibodies against HIV, detection of specific proteins that this virus carries (known as Western blot) and quantitative determination of viral genetic material in the blood (known as viral load). If there is suspicion of HIV infection in the newborn, treatment can be initiated within 6-12 hours after delivery for preventive purposes and drugs that target the enzymes necessary for viral reproduction can be used. Once HIV+ status in infants and children is confirmed, treatment is life-long. This may be challenging from several aspects - adherence to therapy, development of drug resistance and the appearance of adverse effects. For this reason, one of the most important goals in the medical world is the prevention of HIV transmission through early recognition and treatment of HIV-positive individuals.

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