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HIV/AIDS in Children. Ifedayo Adetifa FWACP Paediatrician MRC Laboratories. Introduction. The first cases of AIDS in adults and children were first reported in the US in 1981 and 1982 respectively
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HIV/AIDS in Children Ifedayo Adetifa FWACP Paediatrician MRC Laboratories
Introduction • The first cases of AIDS in adults and children were first reported in the US in 1981 and 1982 respectively • In Africa,Paediatric HIV cases were first identified in Rwanda and the DRC in 1983-1984, in 1985 in Uganda. • The causative organism –Human Immunodeficiency Virus (HIV) was identified in 1984 • Since then, then AIDS and the preceding latent HIV infection have spread widely and assumed pandemic proportions • In the Gambia, first case was reported in 1986
Epidemiology/Pathogenesis/Natural History • Worldwide, UNAIDS estimates HIV prevalence rates 40.3million living with HIV/AIDS worldwide • Deaths 3.1million in 2005 • Sub-saharan Africa has 10% of the world’s population but has two-thirds of the world’s HIV infected population an 90% of al paediatric infections • In the Gambia, the epidemic was initially dominated by HIV-2 but is now driven by HIV-1 since the mid 1990s seroprevalence rate 2-3%, typically rates are <5% in the West African subcontinent while double digit seroprevalence rates up to 20-50% are found in Eastern and Southern Africa
HIV/AIDS is now a major cause of infant and childhood mortality in Africa accounting for 7.7% of deaths in the U5s • It has increased infant mortality and U5 mortality by 19% and 36% respectively • Impact of HIV/AIDS on children • Increased number of deaths, 570,000 in 2005 • HIV related maternal ill health has a negative effect on infant survival. Infant and early childhood mortality in HIV exposed children is 2-5 times higher than in unexposed children
There are 15 million AIDS orphans globally, about 12millio of theses live in sSA. Several African countries have orphan rates due to AIDS as a percentage of all orphans in excess of 50% • Children suffer extreme mental, psychological and social distress in addition to material hardship because of the deepening poverty that inevitably results from sick and dying parents and care givers. So they drop out of school are exploited economically and are at risk of physical and sexual abuse
Modes of HIV transmission • Mother-to-Child-transmission(MTCT)/Parent to Child transmission- 95% of HIV infected infants in Africa acquire HIV during pregnancy/at the time of delivery/postnatally through breastfeeding. • In-utero transmission is 5-6% • Intrapartum/peripartum is 12-14% • Breastfeeding- 12-14% This risk is increased in women who acquired the infection delivery and is 29% vs 14% • Transmission of infected blood or blood products/unsterile injection procedures(WHO estimates this accounts for 2.5% of infections in adults and children) /scarifications from traditional healers and other communal traditional rituals and therapeutic procedures that involve bleeding • Sexual transmission-Common in adolescents, sexually abused children
Pathogenesis-Basic Virology • Infection with the Human Immunodeficiency Virus (HIV) leads to profound immune dysfunction ultimately resulting in the multisystemic clinical manifestations of Acquired Immune Deficiency Syndrome (AIDS) • HIV is a member of the lentiviridae subfamily of retroviruses. These viruses typically cause indolent infections with long periods of clinical latency and weak humoral responses complicated by persistent viraemia • There are 2 strains of HIV; • HIV-1-responsible for nearly all cases worldwide and almost all of paediatric infections. • There are 3 groups of HIV-1 virus, M(Major), N(New or non M non O) and O(outlier).
It also has many subtypes-A, B, C, D, E. Africa has mainly subtypes A&D (East&Central); C(Southern Africa), A Recombinants (West Africa) • Subtype C is more virulent, causes faster disease progression and higher MTCT rates • HIV-2 causes a minority of infection where it is endemic-West Africa(Gambia/Senegal/Guinea Bissau), Mozambique, Angola, India. • Is less transmissible compared to HIV-1, • Rarely a cause of mother to child transmission and • Is associated with a lower viral load and slower rate of immunologic and clinical decline
HIV Structure -Is a RNA virus -Has an outer double lipid layer derived from host cell Membrane -Within this layer are surface glycoprot (gp120) and trans- membrane protein (gp40) which mediate entry of the virus -The core is made up of several proteins the main one is the p24 -The virion contains Enzymes, Reverse Transcriptase,Protease and Integrase. These are targets of therapy
Lifecycle-Steps-Binding,fusion,entry,transcription, integration, replication, budding and maturation
HIV-1 infects monocytes/macrophages, lymphocytes, dendritic cells and CNS microglia cells. They all carry a membrane glycoprotein called the CD4 protein which is the specific primary receptor target for HIV. • CD4 is primarily found on T-lymphocytes • The hallmark of HIV infection is destruction/depletion and dysfunction of CD4 T lymphocytes also called Helper T-cells • CD4 T-cell absolute count/percentage identifies a specific level of immune suppression
Natural History • Clinical Course of illness • Different from that of adults because in children, HIV infection is acquired in the setting of an evolving/immature immune system • As a result, disease progression to AIDS is much more rapid and the duration of each stage is shorter • Perinatally acquired HIV has a poorer diagnosis in resource poor settings because there is increased prevalence of • intercurrent infections, • malnutrition, • lack of access to primary health care, • delayed diagnosis and lack of access to expert HIV care and treatment • Majority of infants develop HIV related symptoms by 6 months following perinatal transmission
Categories of disease progression in perinatally infected infants • Category 1: Rapid progressors, 25-30%, in-utero infections, death by 1 year • Category 2: Symptoms and progression to AIDS by the age of 2 and death by age 3-5 years, 50-60% • Category 3: Long-term survivors, 5-25%, live beyond 8 years • Factors Prognostic of Disease Progression • Maternal VL at delivery • Infection acquired before 4 months of life • Viral set-point/peak viraemia in infant • Severe immunosuppression-low absolute counts/percentage • WHO Stage 4 disease • Very rapid CD4 decline
Clinical Presentation: When to Suspect HIV in Children • The clinical expression of HIV infection in children is highly variable • Some HIV-positive children develop severe HIV-related signs and symptoms in the first year of life; these are associated with a high mortality • Other HIV-positive children may remain asymptomatic or mildly symptomatic for more than a year and may survive for several years
Uncommon Signs in HIV-negative Children • Recurrent infection: three or more severe episodes of a bacterial and/or viral infection in the past 12 months • Oral thrush: punctate or diffuse erythema and white-beige pseudomembranous plaques on the oral mucosa • Chronic parotitis: the presence of unilateral or bilateral parotid swelling (just in front of the ear) for >14 days, with or without associated pain or fever • Generalized lymphadenopathy: the presence of enlarged lymph nodes in two or more extra-inguinal regions without any apparent underlying cause
Uncommon Signs in HIV-negative Children, continued • Hepatosplenomegaly in the absence of concurrent viral infections such as cytomegalovirus (CMV) • Persistent and/or recurrent fever: fever (>38oC) lasting 7 days, or occurring more than once over a period of 7 days • Neurological dysfunction: progressive neurological impairment, microcephaly, delay in achieving developmental milestones, hypertonia, or mental confusion • Herpes zoster (shingles): painful rash with blisters confined to one dermatome on one side • HIV dermatitis - erythematous papular rash
Common Signs in HIV-infected Children (Also common in ill, non-HIV infected children) • Chronic otitis media: ear discharge lasting 14 days or longer • Persistent diarrhea: diarrhea lasting 14 days or longer • Failure to thrive: weight loss or a gradual but steady deterioration in weight gain from the expected growth, as indicated in the child’s growth card • Suspect HIV particularly in breastfed infants <6 months old who fail to thrive
Signs Very Specific to HIV-infected Children Strongly suspect HIV infection if any of the following are present: • pneumocystis pneumonia (PCP) • esophageal candidiasis lymphoid interstitial pneumonia (LIP) • shingles across several dermatomes • Kaposi’s sarcoma These conditions are very specific to HIV-infected children. However, the diagnosis is often very difficult where diagnostic facilities are limited.
WHO Disease Staging System for HIV Infection and Disease in Children • A child is defined as someone under the age of 15. This staging system also requires the presence of HIV infection: HIV antibody for children aged 18 months or more; virological or p24 antigen positive test if aged under 18 months. Clinical Stage 1 • Asymptomatic • Persistent generalized lymphadenopathy Clinical Stage 2 • Hepatosplenomegaly • Papular pruritic eruptions • Seborrhoeic dermatitis • Extensive human papilloma virus infection • Extensive molluscum contagiosum • Fungal nail infections • Recurrent oral ulcerations
Lineal gingival erythema (LGE) • Angular cheilitis • Parotid enlargement • Herpes zoster • Recurrent or chronic RTIs (otitis media, otorrhoea, sinusitis) Clinical Stage 3 Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • Moderate unexplained malnutrition not adequately responding to standard therapy • Unexplained persistent diarrhoea (14 days or more ) • Unexplained persistent fever (intermittent or constant, for longer than one month) • Oral candidiasis (outside neonatal period ) • Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis/periodontitis • Pulmonary TB • Severe recurrent presumed bacterial pneumonia Conditions where confirmatory diagnostic testing is necessary • Chronic HIV-associated lung disease including brochiectasis • Lymphoid interstitial pneumonitis (LIP) • Unexplained anaemia (<80g/l), and or neutropenia (<1000/µl) and or • thrombocytopenia (<50 000/µl) for more than one month Clinical Stage 4 Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations • Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy • Pneumocystis pneumonia • Recurrent severe presumed bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) • Chronic herpes simplex infection; (orolabial or cutaneous of more than one month’s duration)
Extrapulmonary Tuberculosis • Kaposi’s sarcoma • Oesophageal candidiasis • Central nervous system toxoplasmosis (outside the neonatal period) • HIV encephalopathy • Conditions where confirmatory diagnostic testing is necessary • CMV infection (CMV retinitis or infection of organs other than liver, spleen or lymph nodes; onset at age one month or more) • Extrapulmonary cryptococcosis including meningitis • Any disseminated endemic mycosis (e.g. extrapulmonary histoplasmosis, coccidiomycosis, penicilliosis)
Cryptosporidiosis • Isosporiasis • Disseminated non-tuberculous mycobacteria infection • Candida of trachea, bronchi or lungs • Visceral herpes simplex infection • Acquired HIV associated rectal fistula • Cerebral or B cell non-Hodgkin lymphoma • Progressive multifocal leukoencephalopathy (PML) • HIV-associated cardiomyopathy or HIV-associated nephropathy The presumptive diagnosis above is designed for use where access to confirmatory diagnostic testing for HIV infection by means of virological testing (usually nucleic acid testing, NAT) or P24 antigen testing for infants and children aged under 18 months is not readily available.
10-Point Approach for the Management of Children Infected with HIV • Early diagnosis: the two common approaches include clinical methods and laboratory methods • PCP prophylaxis • Growth monitoring • Nutritional supplementation • Treatment of acute illnesses
10-Point Approach, continued • Treatment of opportunistic infections: bacterial, TB, oral and esophageal candida, and dermatophytes • The need and importance of psychosocial support and adolescent care including the issue of timely disclosure to HIV-infected adolescents • Immunizations • Anti-retroviral therapy that is becoming increasingly accessible • Care for HIV/AIDS-infected mothers
Medication Groups Mode of action: antiretroviral drugs (ARVs) act on the HIV by interfering with its reproductive cycle. The main stages of the cycle where these drugs act to inhibit replication of the virus are: • Inhibit reverse transcriptase enzyme to interrupt the production of proviral DNA. ARVs prevent formation of proviral DNA. NRTI and NNRTI act here. • Inhibit maturation of virion by interrupting the protein processing and virus assembly. During this stage protease enzymes are required and protease inhibitors act here.
