HIV Infection in Children and Adolescents

Foreword
Contents
1: Introduction and Epidemiology
	1.1	 History
	1.2	 Epidemiology and Burden of Disease
	1.3	 Funding
	1.4	 Molecular Epidemiology
	1.5	 Continuum of Care
	1.6	 Conclusion
	References
2: Transmission and Immunopathogenesis
	2.1	 Transmission
	2.2	 The Virus
	2.3	 Life Cycle of the Human Immunodeficiency Virus
	2.4	 Immunopathogenesis
	2.5	 Eradication of the Virus
	References
3: Diagnosis of HIV Infection in Children and Adolescents
	3.1	 Introduction
	3.2	 HIV Tests
	3.3	 Diagnostic Complexities
	3.4	 Diagnostic Guidelines
	References
4: Clinical Manifestations
	4.1	 Introduction
	4.2	 The Natural History of Paediatric HIV Infection
	4.3	 Classification of HIV Infection
	4.4	 Signs and Symptoms of HIV Infection
		4.4.1	 Malnutrition and Growth Failure
		4.4.2	 Recurrent Infections
		4.4.3	 Respiratory Disease
		4.4.4	 Tuberculosis
		4.4.5	 Gastrointestinal Tract Disease
		4.4.6	 Neurological Disorders
		4.4.7	 Haematological Abnormalities and Malignancies
		4.4.8	 Cardiovascular Manifestations
			4.4.8.1	 Renal Disease
			4.4.8.2	 Opportunistic Infections
	References
5: Cutaneous Manifestations of HIV in Children
	5.1	 Introduction
	5.2	 Infections
		5.2.1	 Viral Infections
			5.2.1.1	 Herpes Simplex Virus
				Clinical Presentation
				Complications
				Management
			5.2.1.2	 Varicella Zoster
				Complications
				Management
			5.2.1.3	 Herpes Zoster
				Clinical Presentation
				Management
			5.2.1.4	 Molluscum Contagiosum
				Clinical Presentation
				Complications
				Management
			5.2.1.5	 Verrucae
				Plane Warts (Verruca Plana)
				Verruca Vulgaris
				Condyloma Accuminata (Anogenital Warts)
					Management
		5.2.2	 Bacterial Infections
		5.2.3	 Fungal Infections
			5.2.3.1	 Superficial Fungal Infection
				Tinea Infection
					Tinea Capitis
				Clinical Presentation
				Management
					Non-Drug Therapy
					Drug Therapy
					Tinea Corporis, Cruris and Faciei
				Clinical Presentation
				Management
					Tinea pedis
				Clinical Presentation
				Management
					Onychomycosis
				Clinical Presentation
				Diagnosis
				Differential Diagnosis
				Management
				Oral Candidiasis
				Management
	5.3	 Inflammatory Conditions
		5.3.1	 Seborrhoeic Dermatitis
		5.3.2	 Papular Pruritic Eruption of HIV (PPE)
	5.4	 Infestation
		5.4.1	 Scabies
	5.5	 Drug Reaction
		5.5.1	 Steven Johnson Syndrome
	5.6	 Immune Reconstitution Inflammatory Syndrome (IRIS)
	5.7	 Conclusion
	References
6: Respiratory Diseases Amongst HIV Infected Children
	6.1	 Epidemiology
	6.2	 Classification of HIV Related Respiratory Infections and Disease
	6.3	 Clinical Presentation
	6.4	 Upper Airway Diseases
	6.5	 Lower Airways Diseases
		6.5.1	 Etiology of Acute Opportunistic Infections Related to Pneumonia
			6.5.1.1	 Bacterial Infections
			6.5.1.2	 Viral Infections
			6.5.1.3	 Fungal Pneumonia
			6.5.1.4	 Polymicrobial Infection
	6.6	 Aetiology of Chronic Lung Disease
		6.6.1	 Lymphoid Interstitial Pneumonitis (LIP)
		6.6.2	 Kaposi Sarcoma
		6.6.3	 Lymphoma
	6.7	 Risk Factors for Acquiring Respiratory Diseases
	6.8	 Sampling and Laboratory Testing
	6.9	 Treatment of HIV Infected Children with Pneumonia
		6.9.1	 Supportive Care
		6.9.2	 Antimicrobial Therapy
		6.9.3	 Corticosteroids
		6.9.4	 Advance Supportive Management
	6.10	 Complications of HIV Related Lung Disease
		6.10.1	 Chronic Obstructive Airway Disease: Bronchiectasis and Constrictive Bronchiolitis Obliterans
		6.10.2	 Immune Reconstitution Inflammatory Syndrome (IRIS)
		6.10.3	 Malignant Transformation of Lymphoid Interstitial Pneumonitis
	6.11	 Preventative Measures
		6.11.1	 Effective ART
		6.11.2	 Vaccination
		6.11.3	 TB Prophylaxis (TPT)
		6.11.4	 Co-trimoxazole Prophylaxis (CPT)
	6.12	 Prognosis
	6.13	 Follow Up
	References
7: Gastrointestinal Tract
	7.1	 Introduction
	7.2	 Oral Pathology: Periodontal Disease, Ulcers, Pain and Xerostomia
	7.3	 Dysphagia (Difficult Swallowing) and Odynophagia (Painful Swallowing)
	7.4	 Vomiting
	7.5	 Abdominal Pain
	7.6	 Acute Diarrhoea
	7.7	 Persistent or Chronic Diarrhoea
	7.8	 Liver Disease
	7.9	 Malnutrition
	References
8: HIV Related CNS Disorders in Children
	8.1	 Introduction
	8.2	 Epidemiology
	8.3	 Neuropathology of CNS HIV Infection
	8.4	 Neuropsychological Profile of HIV Infected Children
	8.5	 HIV Encephalopathy
		8.5.1	 HIV Encephalopathy Presents with Three Recognized Clinical Developmental Stages
	8.6	 Motor Impairment
	8.7	 Cognitive Impairment
	8.8	 Behaviour and Attention Dysfunction
	8.9	 Language and Communication Disorders
	8.10	 Language Processing Disorders
	8.11	 Articulation Disorders
	8.12	 Symptomatic Epilepsy
	8.13	 CNS Infections
	8.14	 Neuroimaging in HIV CNS Disease
	8.15	 Assessment and Intervention Strategies
		8.15.1	 Medical Management
	References
9: Cardiovascular Manifestation of Paediatric HIV Infection
	9.1	 Paediatric HIV Infection and Myocardial Function
	9.2	 Cardiac Failure in Children with HIV
		9.2.1	 Causes of Cardiomyopathy
		9.2.2	 Clinical Findings
		9.2.3	 Management of Cardiac Failure and Cardiomyopathy
	9.3	 Pericarditis and Pericardial Effusions
	9.4	 Cor Pulmonale and Pulmonary Hypertension
	9.5	 Coronary Artery Disease in HIV Infected Children
	9.6	 HIV Infection and Prolonged Corrected QT Interval
	References
10: Haematological Manifestations of HIV Infection
	10.1	 Introduction
	10.2	 Pathophysiology
		10.2.1	 Effect of Medication on Haemopoiesis
	10.3	 Haematological Changes in Different Phases of Infection
		10.3.1	 In Primary Infection
		10.3.2	 Established Infection
		10.3.3	 Features in AIDS
	10.4	 Anaemia
	10.5	 Abnormalities of Myelopoeisis
	10.6	 Thrombocytopenia
	10.7	 Abnormalities of Coagulation
	10.8	 Effects of Tumours on Haemopoeisis
	10.9	 Peripheral Blood and Bone Marrow Abnormalities
	10.10	 Transfusions in HIV Positive Patients
	10.11	 Conclusion
	References
11: Malignancies
	11.1	 Background
		11.1.1	 AIDS Defining (ADC) and Non-AIDS Defining Cancers (NADC)
	11.2	 Pathogenesis
		11.2.1	 Background Lymphoproliferation
		11.2.2	 Role of Co-infection
		11.2.3	 The Cytokine Syndrome Associated with HHV8/KSHV Inflammatory Cytokine Syndrome (KICS)
	11.3	 Cancers
		11.3.1	 AIDS Defining Cancers (ADC)
			11.3.1.1	 Kaposi Sarcoma (KS)
			11.3.1.2	 Non-Hodgkin Lymphoma (NHL)
				Burkitt’s Lymphoma (BL), Burkitt-Like Lymphoma and High Grade B Cell Lymphomas
				Plasmablastic Lymphoma
				Primary CNS Lymphoma (PCNSL)
			11.3.1.3	 Other B Cell Lymphomas: Primary Effusion lymphoma (PEL)
			11.3.1.4	 Other ADC
		11.3.2	 Non-AIDS Defining Cancers (ADC)
			11.3.2.1	 Hodgkin Disease (HD)
			11.3.2.2	 Leiomyosarcoma
			11.3.2.3	 Intracranial Myopericytoma
		11.3.3	 Incident Cancers (Paediatric Malignancies: Non-AIDS Defining Cancers (NADC))
		11.3.4	 Dual Cancers
	11.4	 Emerging Patterns and Impact of ART
		11.4.1	 Trends Worldwide
		11.4.2	 Local Trends: Late Presenters and Missed Early Diagnosis
		11.4.3	 Cancer in Patients with Restored and or Preserved Immunity
	11.5	 The Future
	References
12: HIV-Related Kidney Diseases
	12.1	 Introduction
	12.2	 Pathogenesis of HIV-Associated Nephropathy
	12.3	 Pathogenesis of HIV Immune Complex Kidney Disease (HIVICK)
	12.4	 Clinical Presentation
	12.5	 Diagnosis of HIV-Associated Nephropathy
	12.6	 Clinical Presentation of Other HIV-Related Kidney Diseases in Children with HIV-Infection
		12.6.1	 Urinary Tract Infection
		12.6.2	 Acute Interstitial Nephritis
		12.6.3	 Vasculitides
		12.6.4	 Thrombotic Microangiopathy (TMA)
		12.6.5	 Electrolyte and Acid-Base Disorders
	12.7	 Treatment of HIV-Associated Nephropathy (HIVAN)
	12.8	 Dialysis in Children with End Stage Kidney Disease Secondary to HIV-Related Kidney Disease
	12.9	 Transplantation in HIV-Infected Children
	References
13: Rheumatological Manifestations of HIV Infection
	13.1	 Introduction
	13.2	 Spectrum of Rheumatological Manifestations
		13.2.1	 Arthralgia
		13.2.2	 Arthritis
			13.2.2.1	 Pathogenesis
			13.2.2.2	 Clinical Presentation
			13.2.2.3	 Management
		13.2.3	 HIV Associated Muscle Disease
			13.2.3.1	 Pathogenesis
			13.2.3.2	 Clinical Presentation
			13.2.3.3	 Treatment
		13.2.4	 HIV Associated Vasculitis
			13.2.4.1	 Pathogenesis
			13.2.4.2	 Clinical Presentation
			13.2.4.3	 Investigations
			13.2.4.4	 Treatment
		13.2.5	 Systemic Lupus Erythematosus
		13.2.6	 Rheumatological Manifestations Associated with Antiretroviral Therapy
		13.2.7	 Serological Abnormalities
	13.3	 Summary
	References
14: Opportunistic Infections
	14.1	 Introduction
	14.2	 Bacterial Infections
		14.2.1	 Pneumonia
	14.3	 Fungal Infections
		14.3.1	 Pneumocystis jirovecii Pneumonia
		14.3.2	 Candida
		14.3.3	 Cryptococcosis
			14.3.3.1	 Clinical Characteristics
			14.3.3.2	 Diagnostic Tests
			14.3.3.3	 Treatment
			14.3.3.4	 Secondary Prophylaxis (Maintenance)
			14.3.3.5	 Screening for at-Risk HIV Positive Patients
	14.4	 Viruses
		14.4.1	 Herpes Simplex Virus (HSV)
		14.4.2	 Cytomegalovirus (CMV)
			14.4.2.1	 Seroepidemiology
			14.4.2.2	 Pathophysiology
			14.4.2.3	 Impact of HIV on Congenital CMV
			14.4.2.4	 The Impact of CMV on HIV Progression
			14.4.2.5	 Clinical Disease in Children with HIV Infection
			14.4.2.6	 Diagnostic Tests
			14.4.2.7	 Treatment
		14.4.3	 Varicella Zoster Virus (VZV)
			14.4.3.1	 Diagnosis and Treatment
		14.4.4	 Hepatitis B
			14.4.4.1	 Epidemiology
			14.4.4.2	 Aetiology and Pathogenesis
			14.4.4.3	 Clinical Characteristics
			14.4.4.4	 Diagnosis
				Serological Diagnosis
				Molecular Methods
			14.4.4.5	 Screening
			14.4.4.6	 Treatment
				Treatment Options for Children [27]
			14.4.4.7	 Prophylaxis
			14.4.4.8	 Prophylaxis in Infants Born to HBsAg Positive Mothers
		14.4.5	 HPV
			14.4.5.1	 Clinical Manifestations
			14.4.5.2	 Main Types Associated with Significant Disease
			14.4.5.3	 Epidemiology
			14.4.5.4	 Risk Factors for Developing Cervical Cancer
			14.4.5.5	 Screening Recommendations
			14.4.5.6	 Diagnosis
			14.4.5.7	 Prophylaxis
		14.4.6	 Rotavirus
	14.5	 Parasitic Infections
		14.5.1	 Giardiasis
		14.5.2	 Syphilis
			14.5.2.1	 Diagnosis, Screening and Treatment
		14.5.3	 Malaria
			14.5.3.1	 The Effect of HIV on Malaria
			14.5.3.2	 Diagnosis
			14.5.3.3	 Treatment
	References
15: Tuberculosis and HIV in Children
	15.1	 Introduction
	15.2	 TB Disease and HIV
	15.3	 The Impact of Improved Vertical HIV Transmission Prevention
	15.4	 The HIV-Exposed Uninfected Child
	15.5	 Impact of ART on TB Disease
		15.5.1	 BCG
		15.5.2	 TB Infection in the HIV+ or HIV Exposed Uninfected Child
		15.5.3	 TB Diagnosis
		15.5.4	 Levels of Certainty for Pulmonary TB Diagnosis
		15.5.5	 Childhood Anti-TB Therapy and ART
		15.5.6	 Drug Resistant TB and HIV
		15.5.7	 The Immune Reconstitution Inflammatory Syndrome
		15.5.8	 TB Meningitis
	15.6	 Conclusion
	References
16: Care and Management of a Neonate Born to an HIV Positive Mother
	16.1	 Introduction
	16.2	 Routes of Transmission and Prevention
	16.3	 Steps to Be Taken When a Baby Is Born to an HIV Positive Mother
		16.3.1	 Examination of the Newborn Baby
			16.3.1.1	 Effects on Growth
			16.3.1.2	 Assess for Hematologic and Metabolic Complications
			16.3.1.3	 Assess for Birth Defects
		16.3.2	 Evaluate for Infections
			16.3.2.1	 Sexually Transmitted Infections (STI)
			16.3.2.2	 Tuberculosis
			16.3.2.3	 Mastitis
			16.3.2.4	 Group B Streptococcal Sepsis
			16.3.2.5	 Hepatitis B
		16.3.3	 PCR Testing
	16.4	 Monitoring of a Neonate Who Is HIV Exposed but Uninfected (HEU)
	16.5	 Feeding Choices
	16.6	 Management of a Neonate Born to an HIV Positive Mother Includes (National South African Consolidated PMTCT Guidelines. Adapted from the WHO Recommendations)
	16.7	 Management of a Neonate Who Is HIV Infected
	16.8	 Additional Care (South African Guidelines)
	16.9	 Conclusion
	References
17: Adolescents with HIV Infection
	17.1	 Definitions
	17.2	 Development
	17.3	 Adolescents and HIV
	17.4	 Adolescent Friendly Services
	17.5	 HIV Testing and Prevention
		17.5.1	 Condoms
		17.5.2	 VMMC
		17.5.3	 Viral Load Suppression
		17.5.4	 Diagnosing and Treating STIs
		17.5.5	 Post Exposure Prophylaxis (PEP)
		17.5.6	 Pre-Exposure Prophylaxis (PrEP)
	17.6	 HIV-Infected Adolescents and ART
	17.7	 Psychosocial Support
		17.7.1	 Adherence
		17.7.2	 Disclosure
		17.7.3	 Mental Health
	17.8	 Sexual and Reproductive Health
		17.8.1	 Pregnancy and Adolescents
	17.9	 Differentiated Care for HIV-Positive Adolescents
	17.10	 Transition
	References
18: General Management
	18.1	 Management of an HIV-Exposed Child
		18.1.1	 Infant Prophylaxis
		18.1.2	 Diagnosis
		18.1.3	 Nutrition
			18.1.3.1	 Breastfeeding
			18.1.3.2	 Milk Formula Feeds
			18.1.3.3	 Opportunistic Infection Prophylaxis
		18.1.4	 Immunization
	18.2	 Management of an HIV-Infected Child/Adolescent
		18.2.1	 Nutrition
		18.2.2	 Opportunistic Infection Prophylaxis
			18.2.2.1	 Co-Trimoxazole Prophylaxis (CTX)
			18.2.2.2	 INH Prophylaxis
			18.2.2.3	 Fluconazole Prophylaxis
		18.2.3	 Immunization
		18.2.4	 Routine/General Care
	References
19: Antiretroviral Treatment
	19.1	 Introduction
	19.2	 Mechanism of Action
	19.3	 Antiretroviral Drugs
	19.4	 Principles of ART Combination
	19.5	 Public Health Vs Individual Patient Management
	19.6	 Dosing
	19.7	 Monitoring
	19.8	 Management of Treatment Failure
	19.9	 HIV Drug Resistance
	References
20: Prevention of Mother to Child Transmission of HIV
	20.1	 Introduction
	20.2	 Pathophysiology
		20.2.1	 Mechanisms of Transmission
		20.2.2	 Timing of Transmission
		20.2.3	 Risk Factors Affecting MTCT Transmission
			20.2.3.1	 Host Factors
			20.2.3.2	 Genetic
			20.2.3.3	 Tissue and Mucosal Integrity
			20.2.3.4	 Obstetric Factors
	20.3	 Epidemiology
		20.3.1	 International Perspective
		20.3.2	 The South African Perspective
	20.4	 Maternal HIV Testing and Identification of Perinatal HIV Exposure
	20.5	 Antepartum Prevention
		20.5.1	 Antiretroviral Drugs
	20.6	 Monitoring
	20.7	 Intra-partum Prevention
		20.7.1	 Intra-partum Antiretroviral Treatment/Prophylaxis
		20.7.2	 Mode of Delivery
	20.8	 Postpartum Prevention
		20.8.1	 Maternal Follow Up
		20.8.2	 Neonatal Follow Up
		20.8.3	 Breastfeeding: Managing Breastfeeding Populations
	20.9	 Barriers to PMTCT
	References
21: The Microbiome in HIV-Infected Children
	21.1	 Introduction
	21.2	 The Maternal Vaginal Microbiome and HIV Transmission
	21.3	 The Microbiome of the Gastrointestinal Tract (GIT)
	21.4	 The Oropharyngeal Microbiome
	21.5	 The Respiratory Tract Microbiome
	21.6	 The Microbiome and HIV Status, Ageing and Comorbidities
	21.7	 Probiotic and Prebiotic Use in HIV-Infected Patients
	21.8	 The Effect of Anti-retroviral Agents (ARV’s) on the Microbiome
	21.9	 The Microbiome of HIV-Exposed Uninfected (HEU) Infants
	21.10	 Conclusion
	References
22: Palliative Care for Children Living with HIV Infection
	22.1	 Introduction
	22.2	 What Is Palliative Care?
	22.3	 What Is Paediatric Palliative Care?
	22.4	 Physical Aspects in Palliative Care
		22.4.1	 Pain
			22.4.1.1	 Assessment of Pain in Children
				FLACC Scale for Preverbal Children
			22.4.1.2	 Management of Pain
				Note on the Use of Morphine
		22.4.2	 Dyspnoea
	22.5	 Psychological and Social Aspects in Palliative Care
		22.5.1	 Problems Associated with a Chronic Illness
		22.5.2	 Problems Associated with HIV Infection Itself
		22.5.3	 Approach to Management
	22.6	 Spiritual and Cultural Aspects of Palliative Care
		22.6.1	 Assessment and Management of Spirituality
	22.7	 Terminal Care
		22.7.1	 Recognising the ‘End’ Is Coming
		22.7.2	 Hospice Care
		22.7.3	 Advance Care Planning
		22.7.4	 Making the Decision to Stop Antiretroviral Medication
		22.7.5	 Symptoms at the End of Life
			22.7.5.1	 Pain at the End of Life
			22.7.5.2	 The Death Rattle
				Management
			22.7.5.3	 Terminal Agitation
				Management
	22.8	 Conclusion
	References
23: Ethical, Legal, and Social Issues
	23.1	 Introduction
	23.2	 Ethical Norms and Values
		23.2.1	 The Four Principles Approach
		23.2.2	 Core Values in Healthcare Practice
		23.2.3	 Ubuntu and Traditional African Communalism
	23.3	 Human Rights Protections
		23.3.1	 International Human Rights Protections
		23.3.2	 Regional Human Rights Protections
		23.3.3	 South African Human Rights Protections
	23.4	 HIV Testing
		23.4.1	 Informed Consent
		23.4.2	 Pre-test and Post-test Counselling
		23.4.3	 Occupational Exposure to a Child’s Body Fluids
	23.5	 Disclosure
		23.5.1	 Confidentiality and Disclosure of a Child’s HIV Status
		23.5.2	 Disclosure of Status to Children
	23.6	 Mandatory Reporting of Abuse
	23.7	 Conclusion
	References