This page intentionally left blank Textbook of Pediatric HIV Care This comprehensive textbook provides the definitive account of effective care for pediatric HIV patients Drawing on the massive and burgeoning published literature from a wide range of sources, this volume summarizes a wealth of information concerning the etiology of the disease and the best clinical care for this vulnerable group It distils the very latest knowledge of virology, immunology, and pathogenesis and uses this to illuminate and explain management recommendations Recently, many new agents for the treatment and prophylaxis of HIV infection and the opportunistic infections that accompany HIV infection have been developed, accompanied by many new ways of monitoring HIV infection in children These new therapies and approaches to management are complicated, but the long-term health of HIV-infected children depends on their meticulously correct application This textbook explains, helps and guides the clinician through all these complexities to facilitate the best possible care for children with HIV infection Dr Steven L Zeichner received his undergraduate and graduate degrees at the University of Chicago He trained in pediatrics and infectious diseases at the Children’s Hospital of Philadelphia He studies the basic biology of HIV and Kaposis, sarcoma-associated herpesvirus, and directs clinical trials of new therapies for HIV-infected children He is based in Bethesda, Maryland, USA Dr Jennifer S Read trained in pediatrics and pediatric infectious diseases (University of Michigan, Johns Hopkins University), tropical medicine (London School of Hygiene and Tropical Medicine), and epidemiology (Harvard University, National Institutes of Health) Her primary research interest is prevention of mother-to-child transmission of HIV, both in the USA and globally Among other awards, Dr Read received the Pediatric Infectious Diseases Society’s Young Investigator Award in 2001 She is based in Bethesda, Maryland, USA Textbook of Pediatric HIV Care Edited by Steven L Zeichner Bethesda, Maryland, USA Jennifer S Read Bethesda, Maryland, USA Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge , UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521821537 © Cambridge University Press 2004 This book is in copyright Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press First published in print format 2005 - - ---- eBook (EBL) --- eBook (EBL) - - ---- hardback --- hardback Cambridge University Press has no responsibility for the persistence or accuracy of s for external or third-party internet websites referred to in this book, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate Every effort has been made in preparing this book to provide accurate and up-to-date information that is in accord with accepted standards and practice at the time of publication Nevertheless, the authors, editors and publisher can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation The authors, editors and publisher therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use For Rachel, Sarah, and Elizabeth For Alex, Samantha, and Geoffrey Contents List of contributors List of abbreviations Foreword Preface page xi xvii xxiii xxv Introduction Part I Scientific basis of pediatric HIV care Normal development and physiology of the immune system Sherilyn Smith and Ann J Melvin HIV basic virology for clinicians 20 Steven L Zeichner The immunology of pediatric HIV disease 40 Elizabeth J McFarland The clinical virology of pediatric HIV disease 59 Paul Palumbo The natural history of pediatric HIV disease 68 Grace M Aldrovandi The epidemiology of pediatric HIV disease 84 Mary Lou Lindegren, Teresa Hammett, and Marc Bulterys Part II General issues in the care of pediatric HIV patients Diagnosis of HIV-1 infection in children 105 Paul Krogstad vii Prevention of mother-to-child transmission of HIV 111 Jennifer S Read Routine pediatric care 384 Kenneth L Dominguez 134 Elaine Abrams and Lisa-Gaye Robinson 10 Immunizations 24 HIV postexposure prophylaxis for pediatric patients 145 Part IV Clinical manifestations of HIV infection in children Rachel Y Moon 25 Cutaneous diseases 11 Prevention of opportunistic infections and other infectious complications of HIV in children 153 168 188 205 244 17 Neurobehavioral function and assessment of children and adolescents with HIV-1 infection 460 468 Gul H Dadlani and Steven E Lipshultz 31 Pulmonary problems Caroline J Chantry and Jack Moye, Jr 455 Ellen R Wald and Barry Dashefsky 30 Cardiac problems Ligia Peralta and Sandra Cely 16 Growth, nutrition, and metabolism 445 Jane C Atkinson and Anne O’Connell 29 Otitis media and sinusitis 197 Bret J Rudy 15 Adolescent reproductive health and HIV 27 Ophthalmic problems 28 Oral health and dental problems John Farley 14 Adolescents and HIV 431 Howard F Fine, Susan S Lee and Michael R Robinson James M Callahan 13 Adherence to antiretroviral therapy in children and youth 26 Neurologic problems Lucy Civitello Russell B Van Dyke 12 Emergency evaluation and care 413 Andrew Blauvelt 479 Lauren V Wood 32 Hematologic problems 499 William C Owen and Eric J Werner 33 Gastrointestinal disorders 269 510 Harland S Winter and Jack Moye, Jr Pamela L Wolters and Pim Brouwers 34 Renal disease 521 Somsak Tanawattanacharoen and Jeffrey B Kopp Part III Antiretroviral therapy 35 Endocrine disorders 530 Daina Dreimane and Mitchell E Geffner 18 Antiretroviral therapy 287 36 Neoplastic disease in pediatric HIV infection Ross McKinney Jr 536 Richard F Little 19 Antiretroviral drug interactions 305 Thomas N Kakuda and Courtney V Fletcher 20 Metabolic complications of antiretroviral therapy in children 319 Carol J Worrell 21 HIV drug resistance 37 Serious infections caused by typical bacteria 334 Frank Maldarelli 22 Initiating and changing antiretroviral therapy Stephen C Piscitelli 377 551 Shirley Jankelevich 38 Tuberculosis 355 Lynne M Mofenson and Leslie K Serchuck 23 Therapeutic drug monitoring Part V Infectious problems in pediatric HIV disease 569 Rohan Hazra 39 Disseminated Mycobacterium avium complex infection Robert N Husson 580 Figure 25.3 White superficial onychomycosis Tinea infection involves the superficial nail plate in this type of fungal nail infection, and is a harbinger of severe underlying immunodeficiency Figure 25.4 KOH prep-dermatophyte Typical hyphae isolated from scales of a superficial dermatophyte infection Figure 25.5 Tzanck prep – herpes simplex infection Multinucleated giant cells scraped from the floor of an erosion caused by herpes simplex virus Similar cells are observed from lesions caused by varicella zoster virus Figure 25.6 Chronic herpes simplex virus infection Chronic ulcerative lesion in a child with AIDS Figure 25.7 Varicella (chicken pox) Varicella may be particularly severe and prolonged in children infected with HIV Figure 25.8 Chronic varicella zoster virus infection commonly occurs as scattered crusted erosions and ulcers in children with AIDS Figure 25.9 Kaposi’s sarcoma Although uncommon in US children with AIDS, Kaposi’s sarcoma can occur in children and lesions appear as violaceous patches, plaques, papules, or nodules Figure 25.10 Verruca vulgaris Warts in HIV-infected children are common and are often resistant to treatment Figure 25.11 Verruca plana (flat warts) Flat warts are relatively common on the face of HIV-infected children and appear as non-inflammatory, smooth, flat-topped papules Figure 25.12 Molluscum contagiosum Smooth dome-shaped papules with central umbilication are classic for molluscum, and are very common in children with HIV disease Figure 25.13 Molluscum prep White material can be expressed from the center of molluscum lesions, placed onto a slide with KOH, and examined for molluscum bodies, which are oval keratinocytes (left side of the picture) infected with molluscum contagiosum virus Figure 25.14 Impetigo Classic presentation of impetigo secondary to Staphylococcus aureus infection in a child with HIV disease Figure 25.15 Norwegian scabies Unlike typical scabies, children with Norwegian scabies have prominent scaly non-pruritic lesions, lesions on the scalp, and numerous mites within lesions Norwegian scabies is a sign of severe underlying immunodeficiency Figure 25.16 Scabies prep-mite Typical appearance of a scabies mite Figure 25.17 Scabies prep-larvae within eggs Typical appearance of scabies larvae within eggshells Figure 25.18 Demodicidosis Prominent scale on the face of a child with AIDS contained numerous Demodex mites and was successfully treated with topical permethrin Figure 25.19 Demodex prep Scales of suspected lesions can be scraped and examined for Demodex mites, which have elongated bodies (compared to scabies mites) and easily recognized legs near the head of the mite Figure 25.20 Insect bites To avoid unnecessary treatment, it is important to distinguish insect bites from cutaneous bacterial or viral infection Lesions are often pruritic, grouped, and located on the distal extremities Figure 25.21 Drug eruption secondary to trimethoprim-sulfamethoxazole Drug eruptions are extremely common in HIV-infected children and often occur 7–14 days following the onset of initial treatment Figure 25.22 Trichomegaly of the eyelashes A peculiar condition observed in children with AIDS, as well as children with other severe underlying immunodeficiencies Figure 27.1 External photograph of molluscum contagiosum involving the eyelids A chronic keratoconjunctivitis can occur with lesions on the eyelid margin Figure 27.2 CMV retinitis A: Retinal photograph of a patient with CMV retinitis involving the optic disc (arrow) with counting fingers vision The patient was treated with intravenous ganciclovir and the vision improved to 20/40 with residual optic disc pallor B: Retinal photograph showing an area of CMV retinitis in the midperiphery This patient was asymptomatic and was diagnosed during a routine screening examination C: Retinal photograph showing CMV retinitis extending from the optic disc to the superior quadrants D: Retinal photograph of the patient shown in Figure 27.2C after treatment with intravenous ganciclovir Note the retinal hemorrhages and necrosis are replaced by an atrophic chorioretinal scar Figure 27.3 Local anti-viral therapy A: Vitrasert implant (Bausch and Lomb, Rochester NY) – delivers ganciclovir for the treatment of CMV retinitis for up to months B: The release of ganciclovir occurs at the base of the implant and clinical trials have shown the implant to be superior in efficacy to systemic therapy for the treatment of CMV retinitis C: External photograph showing the implant through a dilated pupil (arrow) The implant is sutured to the scleral and projects into the vitreous cavity releasing ganciclovir D: External photograph showing an intravitreal injection of ganciclovir into the eye in a patient with refractory CMV retinitis The injections are performed at least weekly under local anesthesia and are not suitable for children under the age of c 15 years without general anesthesia Figure 27.4 Immune recovery uveitis (IRU) A: Retinal photograph of a patient with IRU This patient had inactive CMV retinitis in the periphery, a mild vitritis, reduced visual acuity to 20/60 from cystoid macular edema and an epiretinal membrane; all features commonly seen with IRU B: A fluorescein angiogram retinal photograph of a patient with IRU and reduced visual acuity Leakage of fluorescein in the central macula is consistent with cystoid macular edema, a consistent finding in IRU patients with reduced vision C: A retinal photograph of a patient with IRU with inactive CMV retinitis (arrow) The remarkable finding in this patient was a moderate vitritis obscuring retinal details D: A retinal photograph of a patient with IRU that developed recurrent vitreous hemorrhages A small area of neovascularization is present at the edge of the healed CMV scar (arrow), a less common finding in patients with IRU Retinal details inferiorly obscured by overlying vitreous hemorrhage Figure 27.5 Toxoplasmosis chorioretinitis A: Retinal photograph of a patient with a presumptive diagnosis of CMV retinitis responding poorly to specific anti-CMV medications Patient was referred and workup revealed a positive toxoplasmosis titer B: Retinal photograph of patient discussed in Figure 27.5A With a presumptive diagnosis of toxoplasmosis chorioretinitis, following months of treatment with anti-toxoplasmosis medications, the lesion showed resolution with a chorioretinal scar remaining in the posterior pole Unfortunately, the lesion had extended into the central macula and the vision was reduced to counting fingers C: Retinal photograph of a patient who presented to the ER following a seizure Brain imaging showed a large solitary abscess Ophthalmologic consultation was requested for complaints of reduced acuity in one eye Examination showed an exudative subretinal lesion in the macula not typical of CMV retinitis Further workup revealed a positive toxoplasmosis titer and a brain biopsy confirmed toxoplasmosis D: Retinal photograph of patient discussed in Figure 27.5C Six months following treatment with anti-toxoplasmosis medications, the chorioretinitis resolved with traction of the macula inferiorly Figure 27.6 Progressive outer retinal necrosis (PORN) A External photograph of a patient with zoster ophthalmicus who developed scleral and corneal involvement during the healing phase of the skin disease B: Retinal photograph of the patient discussed in Figure 27.6A He complained of floaters in one eye months after the onset of the zoster ophthalmicus and examination showed a unilateral retinitis involving the deep retinal structures consistent with PORN Note the relative sparing of the retinal vessels and lack of hemorrhage, typical of this disease C: Retinal photograph of a patient with a history of varicella zoster in the T10 dermatome The patient subsequently developed an outer retinal necrosis in both eyes consistent with PORN D: Retinal photograph of the patient discussed in Figure 27.6C The retinitis progressed rapidly towards the macula and within months, this eye had no light perception despite aggressive use of a combination of anti-HSV, HZV, and CMV medications Figure 27.7 HIV microangiopathy A: Retinal photograph showing cotton wool spots and a retinal hemorrhage, common findings in patients with CD4+ lymphocyte counts < 100 cells/L B: Retinal photograph showing a branch retinal vein occlusion, an uncommon manifestation of HIV microangioapathy Figure 27.8 External photograph of a Kaposi’s sarcoma lesion in the medial orbit extending anteriorly These lesions can be treated with systemic chemotherapy or radiation Figure 27.9 Retinal photograph of ddI toxicity associated with didanosine (ddI) therapy The well-circumscribed depigmented lesions with some hyperpigmented borders are typically observed Figure 28.1 Erythematous candidiasis on the gingiva and buccal mucosa of a child with HIV infection Figure 28.2 A 10-year-old child displays oral features typical of HIV infection: oral candidiasis on the lateral border of the tongue and at the corners of mouth, and a large, recurrent herpetic lesion extraorally Figure 28.3 Caries of the primary dentition of an HIV-infected child Caries is evident on the anterior teeth, indicating a very high rate of caries development These lesions may have been prevented by proper feeding practices and good oral hygiene (A) (B) (C) Figure 31.12 Histopathology of pulmonary MALT (mucosa-associated lymphoid tissue) Panel A Low power view, hematoxylin and eosin stain B: bronchiole Panel B High power, hematoxylin and eosin stain GC: germinal center Panel C Immunohistochemical staining for the B cell marker Leu- 22 Histologic findings suggestive of a low-grade lymphoma of MALT: extensive infiltration by a dense lymphoid infiltrate (Panel A) composed of germinal centers (Panel B) with marked plasmacytosis and irregular lymphoid cells characteristic of monocytoid B-lymphocytes Co-expression of Leu-22 by most of the B cells (Panel C) Figure 36.1 Kaposi’s sarcoma involving the skin with associated edema Figure 36.2 Ulcerating nodular lesions in AIDS-Kaposi’s sarcoma Figure 36.3 Child from Uganda with lymphadenopathic form of Kaposi’s sarcoma with conjunctival involvement (Photo courtesy of Dr Sam Mbulaiteye, Viral Epidemiology Branch, National Cancer Institute, NIH) Figure 40.1 Upper gastrointestinal endoscopy showing confluent white-beige plaques on the esophageal mucosa due to Candida albicans ... the care of pediatric HIV patients Diagnosis of HIV- 1 infection in children 105 Paul Krogstad vii Prevention of mother-to-child transmission of HIV 111 Jennifer S Read Routine pediatric care. ..This page intentionally left blank Textbook of Pediatric HIV Care This comprehensive textbook provides the definitive account of effective care for pediatric HIV patients Drawing on the massive... McFarland The clinical virology of pediatric HIV disease 59 Paul Palumbo The natural history of pediatric HIV disease 68 Grace M Aldrovandi The epidemiology of pediatric HIV disease 84 Mary Lou Lindegren,