Textbook of Pediatric HIV Care

Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Dedication......Page 7
Contents......Page 9
Contributors......Page 13
Abbreviations......Page 19
Foreword......Page 25
Preface......Page 27
Introduction......Page 29
PART I: Scientific basis of pediatric HIV care......Page 31
Barriers......Page 33
Dendritic cells......Page 35
MHC molecules......Page 36
Antigen presentation......Page 37
Chemokines......Page 38
1.3 Development and maturation of the immune system......Page 40
Neutrophils......Page 41
T cell help for antibody production......Page 42
DTH......Page 43
B cells......Page 44
REFERENCES......Page 45
SUGGESTED READING......Page 47
2.2 Classification and origin of HIV......Page 48
2.3 HIV virion structure......Page 49
2.4.1 Viral entry into the host cell......Page 51
2.4.2 Reverse transcription......Page 53
2.4.4 Integration......Page 55
Regulation of transcription from the HIV LTR by cellular factors......Page 56
Regulation of transcription by Tat......Page 57
Post-transcriptional regulation of gene expression by Rev......Page 59
2.5 Translation of structural (late) viral messages and post-translational modification of the late viral proteins......Page 60
2.5.1 Virion assembly, budding, and maturation......Page 61
2.5.2 HIV accessory proteins......Page 62
REFERENCES......Page 63
3.1.1 Primary infection......Page 68
3.1.2 Chronic/progressive infection/non-progressive infection......Page 69
3.2.2 Defects in helper T-lymphocyte cell function......Page 70
3.2.5 Defects in antigen-presenting cell function......Page 72
3.2.7 Defects in B lymphocyte function......Page 73
3.2.10 Technique for CD4+ T lymphocyte number and percentage determinations......Page 74
3.2.12 Evaluating prognosis and response to therapy using CD4+ T lymphocyte values......Page 75
3.3 Immune restoration after highly active antiretroviral therapy......Page 77
3.4 Prophylactic HIV-1 vaccination......Page 79
REFERENCES......Page 80
4.1.1 Serology......Page 87
HIV DNA polymerase chain reaction......Page 88
4.2.1 HIV RNA quantitation......Page 89
4.2.3 Predictive value of quantitative plasma viral RNA......Page 90
4.2.4 Additional quantitative assays......Page 91
REFERENCES......Page 92
5.2 Natural history in adults......Page 96
5.3. Relationship between plasma viral concentration, CD4+ cell level and disease progression in adults......Page 97
5.4 Factors associated with progression in adults......Page 98
5.5 Classification of pediatric HIV-1 infection......Page 99
5.6 Natural history of HIV-1 in children......Page 101
5.7 Natural history of HIV-1 infection in children in Africa......Page 102
5.9 Natural history of horizontally acquired HIV infection in pediatrics......Page 103
5.10 Relationship between plasma viral concentration, CD4+ cell level, and disease progression in children......Page 104
5.11 Factors associated with disease HIV-infected children......Page 105
REFERENCES......Page 106
6.2.1 HIV infection and AIDS reporting......Page 112
Sexual transmission......Page 114
HIV/AIDS among women of childbearing age in the USA......Page 115
Trends in mother-to-child transmission of HIV......Page 117
Receipt of prenatal care......Page 118
Offering and acceptance of HIV counseling and testing......Page 119
Cesarean section for the prevention of MTCT of HIV......Page 120
6.2.4 Morbidity and mortality......Page 121
6.3 HIV/AIDS among children globally......Page 124
REFERENCES......Page 125
PART II: General issues in the care of pediatric HIV patients......Page 131
7.1.1 Detection of antibodies to HIV-1......Page 133
7.2.1 Viral p24 antigen detection......Page 134
7.3 Diagnosing HIV 1infection in infants and children......Page 135
7.4 Diagnosis of non-subtype B HIV-1 infection......Page 136
REFERENCES......Page 137
8.3 Risk factors for, and interventions to prevent, mother-to-child transmission of HIV......Page 139
Efficacy of perinatal transmission prophylaxis with antiretroviral drugs......Page 140
Cervicovaginal fluid......Page 146
Breast milk......Page 147
Intrapartum......Page 148
Micronutrient deficiencies......Page 149
Maternal breast pathology and oral candidiasis in children......Page 150
8.4 Strategies for the prevention of mother-to-child transmission of HIV......Page 151
8.4.3 Cesarean section before labor and ruptured membranes......Page 152
8.4.4 Antiretroviral transmission prophylaxis and antiretroviral treatment of HIV-infected pregnant women......Page 153
REFERENCES......Page 157
9.2.1 Perinatal HIV transmission prophylaxis......Page 162
9.3 Care of the HIV-infected pediatric patient......Page 164
9.3.2 Initial evaluation of the HIV-infected pediatric patient......Page 165
HIV disease progression monitoring......Page 167
Treatment of HIV infection......Page 168
Family assessment, support, and education......Page 169
REFERENCES......Page 170
10.3.1 BCG......Page 173
10.3.2 DTaP/DTP......Page 174
10.3.8 MMR......Page 175
10.3.12 Rabies vaccine......Page 176
10.5.2 Hepatitis B......Page 177
REFERENCES......Page 179
11.1 Introduction......Page 181
11.2 Pneumocystis carinii pneumonia......Page 182
11.4 Cryptosporidium and microsporidiosis......Page 187
11.6 Disseminated Mycobacterium avium complex......Page 188
11.7 Bacterial pneumonia, bacteremia, and other invasive bacterial infections......Page 189
11.10 Cryptococcosis, histoplasmosis, and coccidiodomycosis......Page 190
11.13 Varicella-zoster virus......Page 191
11.16 Hepatitis B virus and hepatitis C virus......Page 192
REFERENCES......Page 193
12.2.1 History......Page 196
12.2.2 Physical examination......Page 197
12.2.5 HIV testing in the emergency department......Page 198
12.2.7 Life-threatening presentations......Page 199
12.3.2 Evaluation and treatment of the well-appearing febrile child......Page 200
12.3.3 Evaluation and treatment of the ill-appearing febrile child......Page 202
12.4.1 Causes......Page 203
12.4.3 Pneumocystis carinii pneumonia......Page 204
12.4.6 Therapy......Page 205
12.5.1 Diarrhea......Page 206
Evaluation......Page 207
Therapy......Page 208
Differential diagnosis......Page 209
Therapy......Page 210
Evaluation and treatment......Page 211
12.7 Summary......Page 213
REFERENCES......Page 214
13.1 HIV as a chronic illness......Page 216
13.2.2 The Stages of Change to Model......Page 217
13.3.1 Caregiver self-report......Page 218
13.3.3 Pill counts......Page 219
13.3.7 Appointment keeping......Page 220
13.4 Improving adherence......Page 221
REFERENCES......Page 222
14.2 Epidemiology......Page 225
14.3 Adolescent development......Page 226
14.5 Prevention......Page 227
14.6 Care of the HIV-infected adolescent......Page 229
REFERENCES......Page 231
15.2.1 Delayed puberty......Page 233
15.2.3 Amenorrhea......Page 235
15.2.4 Oligomenorrhea and hyperandrogenism......Page 237
15.2.5 Dysfunctional uterine bleeding......Page 240
Dysmenorrhea......Page 241
Contraception......Page 243
Condoms......Page 244
Oral contraceptives......Page 245
Emergency contraception......Page 248
15.4 Pregnancy......Page 249
15.5.1 Introduction......Page 250
15.5.2 Sexually transmitted diseases and HIV: the role of immunity......Page 251
15.5.4 Bacterial vaginosis......Page 252
15.5.5 Vulvovaginal candidiasis......Page 253
15.5.6 Trichomoniasis......Page 255
Cervicitis......Page 256
Pelvic inflammatory disease......Page 258
HIV, HPV, and cervical dysplasia......Page 259
Uncomplicated human papillomavirus infections......Page 260
Management of cervical lesions......Page 261
15.5.9 Herpes simplex virus......Page 262
15.5.10 Secondary prevention of sexually transmitted diseases......Page 263
REFERENCES......Page 264
16.1 Definitions: malnutrition and growth failure......Page 272
16.2.2 HIV infection......Page 273
16.3.1 Anthropometric measurements......Page 275
16.3.3 Laboratory studies......Page 276
16.3.4 Assessment of body composition and fat distribution......Page 278
16.4 Causes of malnutrition and associated therapies......Page 281
16.4.1 Decreased oral intake......Page 282
16.4.2 Increased nutrient losses......Page 286
16.4.3 Increased nutrient requirements......Page 287
16.4.4 Metabolic and endocrine dysregulation......Page 288
Potential treatments......Page 289
16.5.3 Mitochondrial toxicity......Page 290
16.6 Resource-poor settings......Page 291
REFERENCES......Page 292
17 Neurobehavioral function and assessment of children and adolescents with HIV-1 infection......Page 297
17.1.1 Patterns of HIV-related CNS disease in children......Page 298
Attention......Page 299
Memory......Page 301
Selection of domains for assessment......Page 302
Neurobehavioral assessment......Page 303
Special test administration procedures......Page 304
Differential diagnosis......Page 305
REFERENCES......Page 307
PART III: Antiretroviral therapy......Page 313
18.2 The biology of HIV and antiretroviral therapy......Page 315
Antiviral activity......Page 316
Overview......Page 317
Clinical overview......Page 318
Clinical trials......Page 319
Pharmacokinetics......Page 320
Clinical trials......Page 321
Pharmacokinetics......Page 322
Antiviral effects......Page 323
Pharmacokinetics......Page 324
Clinical Overview......Page 325
Clinical trials......Page 326
Clinical overview......Page 327
Pharmacokinetics......Page 328
18.3.5 Combination antiretroviral regimens......Page 329
REFERENCES......Page 330
19.1.2 Distribution......Page 333
19.1.3 Metabolism......Page 334
19.1.4 Excretion......Page 336
REFERENCES......Page 345
20.2.1 Background......Page 347
20.2.2 Fat redistribution syndrome......Page 348
20.2.3 Abnormalities in lipid and glucose metabolism......Page 350
20.2.5 Proposed mechanisms of NRTI-associated effects......Page 351
Single cut CT or MRI......Page 352
20.2.7 Management......Page 353
20.3.2 Asymptomatic (compensated) hyperlactatemia......Page 354
20.3.4 Decompensated lactic acidosis......Page 355
20.3.5 Delayed manifestations of mitochondrial toxicity......Page 356
REFERENCES......Page 357
21.3 Identification and characterization of HIV drug-resistance mutations......Page 362
Nucleoside associated mutations (NAMs)......Page 365
Q151M complex......Page 367
21.4.3 Protease inhibitors......Page 368
21.4.7 Resensitization and hypersusceptibility......Page 370
21.5.2 Phenotyping......Page 371
21.6 Evidence base for the use of drug-resistance assays in clinical management of HIV infection......Page 374
21.7.3 Resistance testing–practical considerations......Page 375
21.7.5 Cross-resistance to antiviral agents for infections due to other viruses......Page 376
REFERENCES......Page 377
22.2 When should antiretroviral therapy be started?......Page 383
22.2.1 Adults and post-pubertal adolescents......Page 384
22.2.2 Infants, children, and pre-pubertal adolescents......Page 385
HIV-infected infants under 12 months of age......Page 387
22.2.3 Differences between US and European PENTA guidelines for children......Page 388
22.3 What is the recommended initial antiretroviral regimen?......Page 389
Choice of dual NRTI backbone......Page 393
Alternative regimens for initial therapy......Page 394
Insufficient data to recommend for initial therapy......Page 395
22.5 Virologic considerations for changing therapy......Page 396
22.6 Immunologic considerations for changing therapy......Page 397
22.7 Clinical considerations for changing therapy......Page 398
22.8.2 When a change is due to virologic, immunologic, or clinical disease progression......Page 399
22.9 Conclusions......Page 400
REFERENCES......Page 401
23.1 Drugs as TDM candidates......Page 405
23.4 Clinical trials of TDM......Page 406
23.6 Plasma levels and toxicity......Page 407
23.8 Problems, concerns, and unresolved issues......Page 408
23.9 Practical issues for the clinician......Page 409
REFERENCES......Page 410
24.1.3 Studies of the biologic plausibility of PEP......Page 412
24.1.4 Studies of nPEP in pediatric practice......Page 413
24.2.2 Exposures among children in healthcare settings......Page 415
Sexual abuse......Page 416
Discarded needles or syringes......Page 417
24.3 United States PHS occupational postexposure prophylaxis recommendations......Page 418
Evaluation of the source and exposed individuals for evidence of blood-borne infections, including HIV, HBV, and HCV......Page 419
24.3.2 HIV treatment principles used in developing oPEP recommendations......Page 423
Basic and expanded oPEP regimens......Page 424
Timing of initiation and duration of PEP after exposure......Page 425
HIV postexposure counseling and education......Page 426
24.4.2 Principles for pediatric PEP......Page 428
24.4.3 Age-specific considerations for PEP in children......Page 430
Children aged 2–13 years......Page 432
24.5 Summary......Page 433
REFERENCES......Page 434
PART IV: Clinical manifestations of HIV infection in children......Page 439
25.1 General principles......Page 441
Disseminated fungal infection with skin involvement......Page 442
Varicella-zoster virus......Page 447
Molluscum contagiosum virus......Page 449
Scabies......Page 451
Insect bite reactions......Page 454
25.3.2 Dermatitis......Page 456
REFERENCES......Page 458
26.2.1 Opportunistic infections of the CNS......Page 459
26.3.1 Epidemiology......Page 460
26.3.2 Clinical manifestations......Page 461
26.3.3 Neuroradiologic findings......Page 462
26.3.4 Cerebrospinal fluid Studies......Page 463
26.3.7 Neuropathogenesis......Page 464
26.4.1 Antiretroviral therapy......Page 465
26.4.2 Neuroprophylaxis......Page 466
26.5.2 Peripheral neuropathies......Page 467
REFERENCES......Page 468
27.5 Cornea/sclera......Page 473
27.6.1 Cytomegalovirus retinitis......Page 474
27.6.2 Immune recovery uveitis......Page 475
27.6.3 Toxoplasmosis......Page 476
27.6.4 Progressive outer retinal necrosis......Page 477
27.8 Neoplasms......Page 479
27.11 Drug ocular toxicity......Page 480
REFERENCES......Page 481
28.2.2 Herpes infections......Page 483
28.2.3 Other soft tissue infections......Page 484
28.4 Salivary gland pathology......Page 485
28.8 Prevention......Page 486
REFERENCES......Page 487
29.3 Pathogenesis and natural history OF AOM and sinusitis......Page 488
29.5.1 Otitis media......Page 489
29.6 Microbiologic considerations......Page 490
29.7 Treatment of middle ear and sinus infections......Page 491
29.7.1 Sinus infections......Page 493
29.8 Prevention of otitis media and sinusitis......Page 494
REFERENCES......Page 495
30.3 Types of cardiovascular disease......Page 496
30.4 Evaluation of the pediatric HIV patient for cardiovascular problems......Page 499
30.6 Abnormal left ventricular structure and function, cardiomyopathies, and myocarditis......Page 503
30.7 Pericardial effusions......Page 504
30.12 Summary......Page 505
REFERENCES......Page 506
31.1 Introduction......Page 507
31.2.1 Lymphoid interstitial pneumonitis......Page 508
Recurrent invasive bacterial infections......Page 510
Mycobacterial pneumonias......Page 511
31.2.3 Chronic cough......Page 514
31.2.4 Asthma/reactive airway disease......Page 515
31.3.1 Bronchiectasis......Page 517
31.3.2 Spontaneous pneumothorax......Page 518
31.3.5 Malignancy......Page 519
31.4 Approach to evaluation and management of pulmonary disease......Page 521
REFERENCES......Page 524
32.1 Anemia......Page 527
32.3 Thrombocytopenia......Page 530
32.4 Coagulation abnormalities......Page 533
REFERENCES......Page 535
33.2.1 The role of the GI tract in transmission......Page 538
33.2.2 The role of the GI tract in progression of disease......Page 539
33.3 GI problems of HIV-infected children......Page 540
33.4.2 Nausea and vomiting......Page 541
33.4.3 Diarrhea and GI bleeding......Page 544
33.4.4 Hepatomegaly and jaundice......Page 546
33.5 Conclusions......Page 547
REFERENCES......Page 548
34.3 Acid-base disorders......Page 549
34.5 Drug-induced renal complications......Page 550
34.7 Pyuria: infection and interstitial nephritis......Page 551
34.9 HIV-associated glomerular diseases......Page 553
34.11 Treatment for glomerular disease......Page 555
REFERENCES......Page 556
35.1.3 Sex steroid deficiency......Page 558
35.2.1 Proposed mechanisms......Page 559
35.4.1 Proposed mechanisms......Page 560
35.5.2 Diagnostic approach......Page 561
REFERENCES......Page 562
36.2.1 Kaposi’s sarcoma......Page 564
36.2.5 Incidence: HAART and future prospects......Page 565
36.3.1 Kaposi’s sarcoma......Page 566
36.3.2 Non-Hodgkin’s lymphoma......Page 568
36.3.3 Primary central nervous system lymphoma......Page 570
Lymphoproliferative lesions of mucosa-associated lymphoid tissue......Page 571
36.3.6 Antiretroviral therapy and antineoplastic therapy......Page 572
36.4 Summary......Page 573
PART V: Infectious problems in pediatric HIV disease......Page 577
37.1 Introduction......Page 579
37.2 Epidemiology of serious infections in HIV-infected children......Page 580
37.3 Antibiotic resistance in bacterial pathogens......Page 581
37.3.2 Antibiotic resistance in pathogens associated with diarrhea......Page 586
37.4.3 Campylobacter spp.......Page 587
Streptococcus pneumoniae......Page 588
Catheter-associated bacteremia......Page 589
37.5.2 Pneumonia......Page 590
Streptococcus pneumoniae......Page 591
Catheter-related soft tissue infections......Page 592
37.5.6 Septic arthritis......Page 593
37.6 Summary......Page 594
REFERENCES......Page 595
38.2 Pathogenesis......Page 597
38.3 Clinical presentations......Page 599
38.4 Diagnosis......Page 600
38.6 Tuberculosis disease......Page 601
38.8.1 Bacillus of Calmette and Guerin (BCG)......Page 604
REFERENCES......Page 605
39.2 Microbiology......Page 608
39.4 Clinical presentation and diagnosis......Page 609
39.6 Treatment......Page 611
REFERENCES......Page 614
40.2.1 Cutaneous candidiasis......Page 617
40.2.3 Other superficial fungal infections......Page 618
40.3.1 Oropharyngeal candidiasis......Page 621
40.3.2 Esophageal candidiasis......Page 624
40.3.4 Other mucosal fungal infections......Page 625
40.4.2 Cryptococcosis......Page 626
40.5.1 Histoplasmosis......Page 627
REFERENCES......Page 628
41.2.1 Epidemiology......Page 632
41.2.3 Clinical manifestations......Page 633
Gastrointestinal manifestations......Page 634
41.2.4 Diagnosis......Page 635
41.2.5 Treatment......Page 636
41.3.1 Epidemiology......Page 639
41.3.3 Diagnosis......Page 640
41.4.1 Epidemiology......Page 641
VZV-related retinal disease......Page 642
Treatment......Page 643
Epstein–Barr virus......Page 644
REFERENCES......Page 645
42.1 Biology and taxonomy......Page 648
42.3 Pathogenesis......Page 649
42.6 Radiographic features of  Pneumocystis carinii  pneumonia......Page 650
42.7 Diagnosis of Pneumocystis carinii pneumonia......Page 651
Fiberoptic bronchoscopy with bronchoalveolar lavage......Page 652
42.8 Treatment......Page 653
Pentamidine isothionate......Page 654
Trimetrexate glucuronate/Leucovorin......Page 656
42.11 Summary......Page 657
REFERENCES......Page 658
PART VI: Medical, social, and legal issues......Page 661
43 Clinical trials for HIV-infected children......Page 663
43.1 What are clinical trials?......Page 664
43.2 How are clinical trials conducted?......Page 665
43.3 Who runs clinical trials?......Page 667
REFERENCES......Page 669
44.1.2 The risk for HIV transmission to and from children......Page 671
44.1.3 Precautions and HIV transmission......Page 673
44.1.4 General principles for approaching the child with HIV infection outside the hospital......Page 674
Day care centers......Page 675
44.2 Precautions for other infections......Page 677
REFERENCES......Page 678
45.2 Psychosocial concerns......Page 680
45.3 Assessing family needs......Page 681
45.5 Organizational considerations in the psychosocial care of pediatric HIV infection......Page 682
45.6 Social security and Medicaid......Page 683
45.9 Discharge planning......Page 684
45.11 Working with child welfare agencies......Page 686
REFERENCES......Page 687
46.1 Parents’ perspectives: reasons cited for the decision not to disclose......Page 689
46.4 Adolescent disclosure challenges......Page 690
REFERENCES......Page 692
47 Psychosocial factors associated with childhood bereavement and grief......Page 694
47.3 Grief in children who lose a parent......Page 695
47.5 Recommendations for assisting grieving children......Page 697
47.6 Adult grief-grief in parents who lose a child to HIV/AIDS......Page 700
47.10 Conclusion......Page 701
REFERENCES......Page 704
Assessing the rights and responsibilities of non-custodial biological parents......Page 705
Guardianship arrangements......Page 706
Presumptive disability......Page 707
48.2 Conclusion......Page 708
REFERENCES......Page 709
Appendices......Page 711
Formulary: Antiretroviral agents......Page 713
Formulary: Drugs for opportunistic infections associated with HIV......Page 717
NIAID Pediatric AIDS Clinical Trials Group Units-USA......Page 722
NAIDS Pediatric AIDS Clinical Trials Group Units–International......Page 723
NICHD Clinical Trials Network Sites......Page 724
General AIDS information......Page 728
Treatment centered sites......Page 729
International AIDS resources......Page 730
Research-oriented sites......Page 731
Death and bereavement......Page 732
Selected legal resources for HIV-infected children......Page 733
END NOTE......Page 740
Index......Page 741