Sande's HIV/AIDS Medicine (eBook)

Sande’s HIV/AIDS Medicine: Medical Management of AIDS 2012 4
Copyright 5
Contents 6
Preface 8
Contributors 10
Acknowledgments 16
Section 1: Epidemiology and biology of HIV infection 18
Chapter 1: The global epidemiology of HIV/AIDS 20
Overview of the Global Epidemic 20
Measurement of Disease 20
HIV Transmission 22
Sexual transmission 23
Mother-to-child transmission 23
Injection drug use and exposure to contaminated blood 23
Regional review 23
Sub-Saharan Africa 23
South 25
East 25
West 25
Central 25
Europe 25
West 26
East 26
Central 26
North America 26
United States 26
Canada 27
Latin America and the Caribbean 27
Caribbean 27
Central and South America 27
Asia 28
South and Southeast Asia 28
East Asia 28
Central Asia and Middle East 28
References 29
Chapter 2: The origins and diversification of HIV 32
Introduction 32
The Deep Roots of HIV 32
HIV/SIV Nomenclature 34
Where did HIV Enter the Human Population? 35
When did HIV Enter the Human Population? 36
HIV/AIDS: Collateral Damage from Unsafe Medical Practices? 36
The Meaning of Genetic Diversity within HIV-1 Group M 37
Conclusion 39
References 40
Chapter 3: Molecular biology of HIV 42
HIV Entry 42
Early Cytoplasmic Events 44
Crossing the Nuclear Pore 45
Integration 45
Transcriptional Events 46
Expression of Viral Genes 48
Replicating New Viruses 49
Assembly and Budding of HIV Virions 51
Antiviral Host Factors 51
APOBEC3G 51
TRIM5a 52
Tetherin 53
Summary and Perspective 53
Acknowledgments 54
References 54
Chapter 4: The immune response to HIV 62
Introduction 62
General Principles of an Antiviral Immune Response 62
Acquired Immunity to Viral Infections 63
Immune Response to HIV-1 infection 65
Why the Immune Response Fails to Control HIV 67
Escape from neutralizing antibodies 68
Escape from CD8 T cell control 68
CD8 T cell dysfunction 69
Impaired CD4 T cell responses 69
Impaired dendritic cell function 69
Lymphoid structure degeneration 69
Other concomitant infections 69
Evidence for Correlates of Protection to HIV-1 infection 70
Prospects for vaccines 70
Conclusion 71
References 72
Chapter 5: Viral and host determinants of HIV-1 disease progression 76
Introduction 76
Specific (Adaptive) Antiviral Immune Response 76
Humoral immune response 76
Cellular immune response: cytotoxic T lymphocytes 77
Cellular immune response: helper T lymphocytes 77
Chronic Immune Activation and CD4 T Cell Loss 77
CD4 depletion in the gut 78
Viral Factors That Influence Viral Load: Biological Phenotype 78
Evolution of co-receptor use 79
Viral accessory genes 79
Nef 79
Vif 79
Vpr 80
Vpu 80
Host Factors That Influence HIV-1 Acquisition and Disease Progression 80
Human leukocyte antigens 80
Genome-Wide Association Studies 84
Genome-Wide siRNA, cDNA and Gene-Expression Screens on HIV-1 Replication 85
Conclusion 85
References 85
Chapter 6: Acute HIV infection 94
Introduction 94
Pathophysiology 94
CD4 T cell responses 94
CD8 T cell responses 96
Antibody responses 96
Innate immune responses 96
Immune and virological outcomes at resolution of primary infection 96
Virus 97
Co-infection and superinfection 97
Clinical Manifestations 97
Diagnosis 98
Laboratory Testing and Diagnosis 99
Serology 99
Detuned serology and other testing to detect recent infection 99
Detection of virus 101
p24 Antigen detection 101
Nucleic acid testing 101
Viral load during primary infection 101
Drug resistance testing 102
Management 102
Conclusion 102
References 103
Chapter 7: Biology of HIV-1 transmission 106
Introduction 106
Factors in the Infecting Partner that Determine the Likelihood of Transmission 106
Factors in Viral Selection 107
Endogenous Host Factors 108
Host genetics 108
Exogenous Host Factors 108
STDs, female hormones, male circumcision 108
Early Target Cells and Initial Virus-Host Dynamics 109
Superinfection 109
Re-infection by HIV-1 from another source partner 109
Preventing HIV-1 Transmission 110
Acknowledgments 110
References 110
Section 2: Prevention, diagnosis, and treatment of HIV infection 112
Chapter 8: The design of a global HIV vaccine 114
HIV Biology 114
Pathogenesis of Acute HIV-1 Infection 115
Features of Transmitted Viruses 115
Challenges to HIV Vaccine Development 115
What makes an HIV vaccine different? 115
Subtype diversity 116
Animal models 116
Defining protective immune responses 117
Correlates from monkey studies 117
Human HIV Vaccine Trials 118
Human efficacy trials 118
HIV vaccine concepts 119
Subunit vaccines 119
DNA and viral vectors 119
The future 119
References 124
Chapter 9: HIV prevention 130
Introduction 130
Preventing Sexual Transmission 130
Abstinence 130
Be faithful 131
Condoms 131
Counseling and testing 131
Medical male circumcision 132
STD screening and treatment 132
Antiretroviral microbicides for prevention of male-to-female transmission 132
Oral antiretroviral pre-exposure prophylaxis for prevention of male-to-male transmission 133
"Treatment for prevention" strategy 133
Integration of behavioral prevention programs into AIDS treatment services (prevention for positives) 134
Preventing Mother-to-Child Transmission 134
Preventing Blood-Borne Transmission 134
Harm reduction for injection drug users 134
HIV screening of the blood supply for safe transfusions 135
Universal precautions and nosocomial transmission 135
Antiretrovirals for post-exposure prophylaxis 135
HIV Prevention Strategies under Development 136
Vaccines 136
Combination prevention 136
Conclusion 136
References 137
Chapter 10: Laboratory testing for HIV infection 140
Introduction 140
Diagnostic Testing 140
Monitoring Patient Health 142
Tests for estimating T lymphocytes 142
Routine laboratory testing 143
Monitoring Viral Replication 143
Viral load testing 143
Monitoring drug resistance mutations 145
Tests for treatment selection 146
Quality Assurance and Quality Control 146
References 147
Chapter 11: Overview of antiretroviral therapy 150
Introduction 150
The Natural History of HIV Infection 150
The HIV Life Cycle 151
Early targets in the HIV life cycle 151
Middle targets in the HIV life cycle 151
Late targets in the HIV life cycle 151
Components of ARV Regimens 152
An Overview of Common Components of ARV Regimens 152
NRTIs 152
Lamivudine (3TC) and emtricitabine (FTC) 152
Dual NRTI backbones: co-formulations 152
Tenofovir (TDF) plus emtricitabine (FTC) 152
Abacavir (ABC) plus lamivudine (3TC) 152
Zidovudine (ZDV) plus lamivudine (3TC) 161
Comments on other NRTIs 161
Stavudine (d4T) 161
Didanosine (ddI) 161
Cornerstone agents 161
Non-nucleoside RTIs 161
Efavirenz (EFV) 161
Nevirapine (NVP) 161
Other NNRTIs 162
Etravirine (ETR) 162
Rilpivirine (RPV) 162
Protease inhibitors (PIs) 162
Atazanavir (ATZ) 162
Darunavir (DRV) 162
Other PIs 162
Lopinavir (LPV)/ritonavir (RTV) 162
Integrase inhibitors 162
CCR5 antagonists 163
Fusion inhibitors 163
Clinical Application of ART 163
ARV regimen design 163
Pretreatment assessment 163
Optimal timing of initial ARV therapy 163
Monitoring ART 164
Virologic Failure 164
Specific management approaches in virologic failure 165
Non-adherence to prescribed regimen 165
Toxicity to selected drugs 165
Topics in "Late" Salvage ARV Therapy 165
Adding a new drug to a "failing" regimen 165
ARV Treatment Approaches in Resource-Constrained Settings 166
ARVs as pre-exposure prophylaxis 166
References 166
Chapter 12: Development and transmission of HIV drug resistance 172
Introduction 172
Generation of HIV-1 Drug Resistance 173
Inhibitors of Reverse Transcriptase 174
Protease Inhibitors 176
Fusion and Entry Inhibitors 176
Antiretroviral Drug Resistance in Non-B Subtypes of HIV-1 Group M 177
Transmission of HIV Drug Resistance 177
Conclusion 179
References 179
Chapter 13: Pharmacology of antiretroviral drugs 186
Introduction 186
Antiretroviral Drugs 186
Pharmacokinetic Definitions 187
Drug Metabolism 188
Intracellular phosphorylation 188
Drug Transport Proteins 188
Cytochrome P450 enzymes 189
Enzyme inhibition and boosted protease inhibitor therapy 189
Enzyme inhibition and drug interactions 189
Enzyme induction and drug interactions 190
Endemic diseases and drug interactions 190
Drug-food interactions 190
Drug-traditional medicines interactions 191
Special Populations 191
Renal and hepatic impairment 191
Low-weight individuals 191
Pediatrics 192
Pregnancy 192
Ethnic variations in pharmacokinetics 192
Conclusion 192
Acknowledgments 192
References 192
Chapter 14: Complications resulting from antiretroviral therapy for HIV infection 194
Introduction 194
Adverse Effects of Antiretroviral Treatment in the Early Phase of Therapy 194
Abacavir hypersensitivity reactions 195
Nevirapine hypersensitivity reactions 197
Other potential pharmacogenetic strategies for preventing early treatment discontinuation 197
Adverse Effects of Antiretroviral Treatment during Long-Term Therapy 198
Complications of nucleoside and nucleotide reverse transcriptase inhibitor (NRTI) therapy 198
Tenofovir renal safety 198
Lactic acidosis, hyperlactatemia, and acute hepatic steatosis 199
Pancreatitis 199
Non-cirrhotic portal hypertension 199
Neuropathy 199
Hematological complications of NRTI therapy 200
Lipoatrophy 200
Complications of HIV protease inhibitor therapy 202
Abnormal liver function/liver enzyme abnormalities 202
Gastrointestinal intolerance 202
Nephrolithiasis and renal dysfunction 202
Metabolic complications: dyslipidemia and insulin resistance 202
Toxicity Profiles of NNRTIs 202
Efavirenz and central nervous system side effects 202
Rash 203
Impact of Antiretroviral THERAPY on Prevalent Diseases Associated with Aging 203
Cardiovascular Risk and HIV infection 204
Metabolic profile in the 'pre-treatment' phase: background risk and the influence of HIV infection 204
Metabolic profile in the 'treatment' phase: metabolic complications of specific antiretroviral drugs 204
Monitoring and managing cardiovascular risk: incorporating multiple risk factors 204
Bone Density and HIV infection 205
Conclusion 205
References 206
Section 3: Diseases associated with HIV infection 210
Chapter 15: Oral complications of HIV infection 212
Introduction 212
Candidiasis (Oral Candidosis) 212
Treatment 215
Gingivitis and Periodontitis 216
Other Bacterial Lesions 217
Viral Lesions 217
Herpes simplex 217
Herpes zoster 217
Cytomegalovirus ulcers 217
Hairy leukoplakia 217
Warts 218
Neoplastic Disease 218
Kaposi's sarcoma 218
Lymphoma 219
Carcinoma 219
Other Lesions 219
Conclusion 220
References 220
Chapter 16: Ocular manifestations of AIDS 224
Introduction 224
Epidemiology 224
Non-infectious Retinal Vasculopathy 224
Diseases of the anterior segment 225
Disorders of the posterior segment 226
Neuro-ophthalmologic disorders 229
Neoplastic disorders 230
Drug-induced ocular complications 231
Future directions 231
Conclusion 232
References 232
Chapter 17: Global HIV and dermatology 236
Skin Disease in HIV 236
Primary HIV 236
Pigmentation 236
Itching 237
Staphylococcal aureus Skin Infections 238
Bacillary Angiomatosis 238
Cancrum Oris 239
Syphilis 239
Cutaneous Tuberculosis 240
Leprosy 240
Nocardiosis 240
Leishmania 240
Superficial Fungal (Dermatophyte) Infections 241
Tinea of the Skin, Hair, and Nails 241
Deep (Systemic) Fungal Infections 241
Cryptococcosis 241
Histoplasmosis 241
Sporotrichosis 242
Aspergillosis 242
Penicillium 242
Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV) 242
Human Papillomavirus (HPV) 242
Malignancies of the Skin 243
Psoriasis 243
Seborrheic dermatitis 243
Xerosis and Atopic Dermatitis 244
Recurrent Aphthous Stomatitis 244
Drug Eruptions 244
References 245
Chapter 18: Gastrointestinal disorders in HIV including diarrhea 254
Introduction 254
Gut-Associated Lymphatic Tissue (GALT) 254
Esophageal Disorders 254
Gastric Disorders 255
Diarrhea 258
Anorectal Disorders 260
Conclusion 261
References 262
Chapter 19: Primary neurological manifestation of HIV/AIDS 266
Introduction 266
Epidemiology 267
Pathophysiology, Pathogenesis, and Genetics 267
HIV-Associated Neurocognitive Disorders (HAND) 268
Clinical features 268
Diagnosis 269
Treatment 269
HIV Neuropathy 271
Clinical features 271
Diagnosis 271
Treatment 271
HIV-1-Associated Vacuolar Myelopathy 272
Clinical features 272
Diagnosis 272
Treatment 272
Conclusion 272
References 272
Chapter 20: Psychiatric barriers and the international AIDS epidemic 274
Introduction 274
Chronic Mental Illness and HIV Infection 276
Mood Disorders in HIV/AIDS 277
HIV-associated neurocognitive disorders 277
HIV and Substance Abuse 278
Personality, Temperament, and HIV 278
Psychopharmacology in HIV-Infected Individuals 279
Conclusion 281
References 281
Chapter 21: Cardiovascular complications of HIV infection 284
Introduction 284
Coronary Artery Disease 284
Cardiomyopathy and Congestive Heart Failure 286
Pericardial Disease 287
Pulmonary Hypertension 288
Endocarditis 288
Neoplasms 289
Conclusion 289
Acknowledgment 289
References 289
Chapter 22: Endocrine complications of HIV infection 292
Introduction 292
The Thyroid 292
Thyroid pathology 292
Alterations in thyroid function 292
Effects of antiretroviral and other therapies 293
Treatment considerations 293
The Adrenal 294
Adrenal pathology 294
Alterations in adrenal function 294
Effects of antiretroviral and other therapies 294
Treatment considerations 295
The Pancreas 295
Pancreatic pathology 295
Alterations in glucose homeostasis and effects of antiretroviral therapy 295
Effects of other therapies 296
Treatment considerations 296
Abnormalities of Lipid Metabolism 296
Effects of antiretroviral drugs and other therapies 296
Treatment considerations 297
Bone 297
Bone pathology 297
Alterations in bone and mineral metabolism 297
Effects of antiretroviral and other therapies 297
Treatment considerations 298
Reproductive Health in Men 298
Testicular pathology 298
Alterations in sex hormones 298
Effects of antiretroviral and other therapies 299
Treatment considerations 299
Fertility and reproduction 299
Reproductive Health in Women 299
Ovarian pathology 299
Ovarian function and alterations in sex hormones 299
Effects of antiretroviral and other therapies 300
Treatment considerations 300
Fertility and reproduction 300
The Pituitary 300
Pituitary pathology 300
Alterations in pituitary function 300
Somatotropic axis 300
Effects of antiretroviral and other therapies 301
Wasting Syndrome 301
Treatment considerations 301
References 302
Chapter 23: Renal complications of HIV infection 304
Introduction 304
Overview of Global Healthcare/Delivery 304
Epidemiology 304
Racial distribution of HIVAN 305
Patterns of renal disease in Africa 305
Natural History 306
Pathogenesis 306
Pathology 306
Clinical Features 307
Patient evaluation, diagnosis, and differential diagnosis 308
Treatment 308
Antiretroviral therapy 308
Angiotensin-converting enzyme inhibitors 308
Steroids 310
Renal replacement therapy 310
Course and Outcome 310
Conclusion 311
References 311
Chapter 24: Pneumocystis pneumonia 314
Introduction 314
Epidemiology 314
Risk Factors for Pneumocystis Pneumonia 314
Clinical Features 322
Symptoms and Signs 322
Laboratory Tests 322
Chest Radiograph 322
Other Tests 323
Diagnosis 323
Treatment 325
Prophylaxis 326
Conclusion 328
References 328
Chapter 25: Other HIV-related pneumonias 330
Introduction 330
Frequency 330
Bacterial Pneumonia 330
Pneumococcal pneumonia 330
Haemophilus influenzae 331
Staphylococcus aureus 333
Pseudomonas aeruginosa 333
Atypical agents 333
Miscellaneous pathogens 333
Diagnostic approach 334
Treatment 334
Fungal Pneumonia 334
Aspergillosis 334
Cryptococcosis 337
Histoplasmosis 338
References 338
Chapter 26: HIV-associated tuberculosis 342
Introduction 342
Epidemiology 342
Pathogenesis and Natural History 344
Transmission of M. tuberculosis 344
M.. tuberculosis infection 345
TB disease 345
Immunologic aspects 346
Impact of TB infection on HIV 346
Clinical Manifestations 346
Primary tuberculosis 346
Occult primary tuberculosis 346
Uncomplicated primary tuberculosis 347
Primary tuberculosis with complications 347
Secondary tuberculosis 347
Pulmonary tuberculosis 347
Extrapulmonary tuberculosis 348
Miliary TB 348
TB meningitis 350
TB lymphadenitis 350
Pleural TB 350
TB peritonitis 350
Gastrointestinal TB 350
TB pericarditis 350
Renal TB 351
Vertebral osteomyelitis 351
Diagnosis 351
Diagnosis of latent TB infection (LTBI) 351
Tuberculin skin test 351
Interferon-gamma releasing assays (IGRAs) 351
Diagnosis of active pulmonary tuberculosis 352
Clinical symptoms 352
Chest radiography 352
Sputum microscopy 352
Mycobacterial culture 353
Nucleic acid amplification tests (NAATs) 353
Line probe assays (LPAs) 353
Phage-based assays 354
Serologic, antibody detection tests 354
Antigen detection tests 354
Serum biomarkers 354
Treatment 354
Treatment of TB in special populations 355
Pregnancy or breastfeeding 355
Liver disease 355
Renal disease 356
Pyridoxine 356
New drugs 356
Fluoroquinolones 356
Diarylquinolines 357
Nitroimidazoles 357
Ethylenediamines 357
Oxazolidinones 358
Rifamycins 358
Special issues of treatment in HIV-infected individuals 358
Co-administration of TB and HIV treatment 358
Drug-drug interactions 359
Rifampicin and efavirenz 359
Rifampicin and nevirapine 359
Rifampicin and protease inhibitors 359
Rifampicin and other antiretroviral agents 359
Rifabutin and ART 359
Immune reconstitution inflammatory syndrome (IRIS) 359
Timing of ART initiation 360
Mortality in HIV-associated tuberculosis 360
TB Prevention 361
Treatment of latent tuberculosis and secondary prevention 361
BCG vaccination 361
Control Strategies 362
References 362
Chapter 27: Disseminated Mycobacterium avium complex and other atypical mycobacterial infections 366
Epidemiology 366
Disseminated MAC in industrialized countries 366
Disseminated MAC in resource-poor countries 366
Effect of MAC prophylaxis and ART on incidence 366
Acquisition of MAC infection 367
Pathogenesis 367
Clinical Manifestations 367
Effect of disseminated MAC infection on survival in AIDS 367
Clinical presentation of disseminated MAC 367
MAC immune reconstitution inflammatory syndrome 368
Diagnosis 368
Therapy 368
Macrolides: clarithromycin and azithromycin 369
Ethambutol 369
Rifabutin 369
Optimal combination treatment regimens 370
Management of Treatment Failure 370
Drug interactions with antiretroviral medications 371
Initiating antiretroviral therapy and stopping MAC treatment after immune restoration 371
Empiric treatment for disseminated MAC and tuberculosis 371
Prophylaxis 371
Clarithromycin 371
Azithromycin 372
Rifabutin 372
Discontinuation of primary prophylaxis 372
Other Atypical Mycobacterial Infections in HIV-Infected Patients 372
M. kansasii 372
M. genavense 372
M. haemophilum 373
References 373
Chapter 28: Candida in HIV infection 376
Epidemiology 376
Clinical Manifestations 377
Oropharyngeal candidiasis 377
Esophageal candidiasis 377
Vulvovaginal candidiasis 378
Disseminated candidiasis and candidemia 378
Diagnosis 378
Treatment 379
Azoles 379
Fluconazole 379
Itraconazole 379
Voriconazole and posoconazole 380
Cell wall synthesis inhibitors (caspofungin, anidulafungin, and micafungin) 380
Polyenes 381
Treatment of oropharyngeal and esophageal candidiasis 381
Oropharyngeal candidiasis 381
Esophageal candidiasis 381
Treatment of vulvovaginal candidiasis 381
Treatment of candidemia 382
Candida and ART 382
Prevention of Candida Infections 382
References 382
Chapter 29: Cryptococcosis and other fungal infections (histoplasmosis and coccidioidomycosis) in HIV-infected patients 386
Introduction 386
Cryptococcus 386
Microbiology 386
Epidemiology 386
Natural history, pathogenesis, and pathology 387
Clinical features 387
Cryptococcal Meningoencephalitis 387
Patient evaluation, diagnosis, and differential diagnosis 387
Prognosis 389
Treatment 390
Cerebral cryptococcomas 392
Management of elevated intracranial pressure 392
Relapses 393
Timing of ART and IRIS 393
Extraneural Cryptococcosis 393
Diagnosis 393
Treatment 393
Primary fungal prophylaxis 394
Histoplasmosis 394
Microbiology 394
Epidemiology 394
Natural history, pathogenesis, and pathology 394
Clinical features 395
Patient evaluation, diagnosis, and differential diagnosis 395
Treatment 395
Coccidioidomycosis 397
Epidemiology 397
Natural history, pathogenesis, and pathology 397
Clinical features 397
Patient evaluation, diagnosis, and differential diagnosis 398
Treatment 398
References 399
Chapter 30: Infection due to Penicillium marneffei 406
Introduction 406
Epidemiology 406
Natural History and Pathogenesis 407
Clinical Features 408
Patient Evaluation, Diagnosis, and Differential Diagnosis [32] 409
Treatment 410
References 411
Chapter 31: AIDS-associated toxoplasmosis 414
Introduction and Epidemiology 414
Clinical Presentation 414
Congenital toxoplasmosis and the HIV-infected woman 415
Diagnosis 416
Serology 416
Isolation studies 416
DNA detection (PCR) 417
Neuroimaging studies 417
Histopathology 417
Differential Diagnosis 418
Management 418
General principles 418
Primary (induction) therapy 420
Maintenance treatment (secondary prophylaxis) 421
Considerations during pregnancy 421
Prevention (primary prophylaxis) 422
Discontinuation of primary and secondary prophylaxis 423
References 423
Chapter 32: Hepatitis virus infections 428
Introduction 428
Epidemiology 428
Natural history 429
Hepatitis A 429
Hepatitis B 429
Hepatitis C 429
Hepatitis D 430
Hepatitis E 430
Patient Evaluation 430
Diagnosis 431
Treatment 431
HBV therapy 431
Acute HCV 432
Chronic HCV 432
HDV 434
HEV 434
Antiretroviral-Associated Hepatotoxicity 434
Liver Transplantation 435
Summary 435
References 435
Chapter 33: Bartonella infections in HIV-infected individuals 438
Historical Perspective 438
Clinical Presentation of Bartonella Infections 438
Cutaneous bacillary angiomatosis 439
Osseous bacillary angiomatosis 439
Splenic and hepatic bacillary peliosis 440
Gastrointestinal and respiratory tract bacillary angiomatosis 441
Lymph node bacillary angiomatosis 441
Central nervous system manifestations of Bartonella infection 441
Unusual bacillary angiomatosis presentations 441
Bacteremia with Bartonella species and fever of unknown origin 441
Diagnosis of Bartonella Infections 442
Histopathological diagnosis 442
Obtaining tissue for diagnosis 442
Histopathological characteristics 442
Serological diagnosis 443
Culture of Bartonella species from blood and tissue of patients with BA 443
Treatment of Bartonella Infections 443
Choice of antibiotics 443
Treatment of cutaneous bacillary angiomatosis lesions 445
Treatment of osseous bacillary angiomatosis lesions 445
Treatment of hepatic and splenic bacillary peliosis 445
Treatment of Bartonella bacteremia 445
Relapse 445
Epidemiology and Prevention of Bartonella Infections 446
Acknowledgments 446
References 447
Chapter 34: Management of herpesvirus infections (cytomegalovirus, herpes simplex virus, and varicella-zoster virus) 450
Cytomegalovirus 450
General comments 450
Chorioretinitis 450
Nervous system 451
Polyradiculopathy and myelitis 451
Encephalitis with dementia and ventriculoencephalitis 452
Mononeuritis multiplex 452
Painful distal neuropathy 452
Gastrointestinal system 453
Pulmonary system 453
Treatment of CMV infection 454
Ganciclovir/valganciclovir 454
Structure and mechanism of action 454
Pharmacology and dosage 454
Clinical use 455
Resistance 455
Toxicity 455
Effects on hematopoiesis 455
Toxicities in other organ systems 456
Gonadal toxicity 456
Teratogenesis 456
Foscarnet 456
Pharmacology 456
Ganciclovir and foscarnet 456
Cidofovir 457
Immune recovery uveitis 457
Herpes Simplex Virus 457
Clinical presentation 457
Orolabial infection 458
Genital infection 458
Anorectal infection 458
Esophagitis 459
Encephalitis 459
Drug-resistant HSV infection 460
Treatment of HSV infection 460
Acyclovir 460
Valacyclovir 461
Famciclovir 461
Foscarnet 462
Other antiviral drugs 462
Management of patients with HSV infection 462
Suppressive antiviral therapy for HSV infection 463
Management of drug-resistant HSV infection 464
Varicella Zoster Virus 464
Primary infection varicella 464
Herpes zoster 464
Complications 465
Management of VZV infection 465
Treatment of drug-resistant VZV infection 466
Prevention of VZV infection 466
Conclusion 466
References 467
Chapter 35: HIV-associated malignancies 472
Introduction 472
Epidemiology of HIV-Associated Malignancies 472
Lymphoproliferative Disease 473
Non-Hodgkin's lymphoma 473
Systemic NHL 473
Clinical management 473
Infusional chemotherapy 474
Use of rituximab 474
Hematopoietic cell transplantation for HIV-NHL 474
Primary CNS lymphoma 474
Hodgkin's lymphoma 475
Other lymphoproliferative disease in HIV infection 475
Primary effusion lymphoma (PEL) 475
Plasmablastic lymphoma 475
Multicentric Castleman's disease 475
Kaposi's Sarcoma 476
Pathogenesis 476
Clinical presentation 476
Clinical management 476
Local therapies 476
Radiotherapy 476
Alitretinoin gel 476
Intralesional vinblastine 477
Cryotherapy 477
Systemic therapy 477
Chemotherapy 477
Interferon-a 477
Investigational agents 478
Cervical Cancer 478
Epidemiology 478
Etiology 478
Screening and diagnosis 478
Treatment 478
Anal Cancer 479
Etiology 479
Screening 479
Treatment 479
Non-AIDS-Defining Malignancies 479
Clinical features 479
Treatment 479
Acknowledgments 479
References 480
Chapter 36: STDs and syphilis 484
Introduction 484
Syphilis 484
Epidemiology 484
Natural history, pathogenesis, and pathology 484
Clinical features 485
Patient evaluation, diagnosis, and differential diagnosis 485
Treatment 486
Genital Herpes 487
Epidemiology 487
Natural history, pathogenesis, and pathology 488
Clinical features 488
Patient evaluation, diagnosis, and differential diagnosis 488
Treatment 489
Gonorrhea 489
Epidemiology 489
Natural history, pathogenesis, and pathology 490
Clinical features 490
Patient evaluation, diagnosis and differential diagnosis 490
Treatment 490
Chlamydia 492
Epidemiology 492
Natural history, pathogenesis, and pathology 492
Clinical features 492
Patient evaluation, diagnosis, and differential diagnosis 492
Treatment 493
Trichomoniasis 493
Epidemiology 493
Natural history, pathogenesis, and pathology 494
Clinical features 494
Patient evaluation, diagnosis, and differential diagnosis 494
Treatment 494
Syndromic Management 494
Introduction 494
Genital ulcers (Fig. 36.7A) 494
Urethral discharge (Figs. 36.7B and 36.7C) 495
Vaginal discharge (Fig. 36.7D) 496
References 497
Section 4: Prevention and management 500
Chapter 37: Prevention of mother-to-child transmission of HIV-1 502
Introduction 502
Risk Factors for HIV-1 MTCT 502
In utero and intrapartum transmission 502
Postnatal transmission 503
Antiretroviral Interventions to Prevent HIV-1 MTCT 503
Mechanisms of action of antiretroviral prophylaxis 504
Clinical trials for prevention of HIV-1 MTCT 504
Short- and Long-Term Safety of Antiretroviral Exposure for Infants and Women 513
Infant 513
Pregnant woman 514
Antiretroviral Drug Resistance 514
Non-antiretroviral Interventions 515
Elective cesarean delivery 515
Current Guidelines for Prevention of MTCT for the United States 515
Current Guidelines for Prevention of MTCT for Resource-Constrained Settings 518
Summary 518
References 521
Chapter 38: Managing HIV infection in children and adolescents 526
Epidemiology 526
Natural History 526
Timing of infection 526
Predicting progression 527
Early Diagnosis and Management of the Exposed Infant 527
Diagnosis of HIV infection 527
Monitoring in the HIV-exposed or HIV-infected infant 528
Vaccination 529
Antiviral Therapy 529
Principles of therapy 529
When to start 530
Initial therapy 532
When to change 532
Resistance testing 534
Therapeutic drug monitoring 534
Use of PCP Prophylaxis 534
Prophylaxis of other opportunistic infections 534
Management 534
Adolescents 534
Unanswered Questions 535
References 535
Chapter 39: Special issues regarding women with HIV infection 538
Nature of the HIV Epidemic among Women 538
Transmission of HIV to Women 539
The Natural History of HIV in Women 542
Clinical Manifestations of HIV in Women 543
Acute infection 543
Cancer 544
Hepatitis C 544
Body habitus and metabolic changes 544
Osteopenia and osteoporosis 544
Thyroid dysfunction 544
Cardiovascular and cerebrovascular disease 544
Woman-Specific Conditions and HIV 545
Cervical cancer and genital epithelial dysplasia 545
Anal cancer 545
Other gynecological conditions 546
Breast cancer 546
Menopause 546
Antiretroviral Treatment of Women 547
Conclusions 548
References 548
Chapter 40: HIV disease among substance users 554
Epidemiology 554
HIV Disease in Drug Users 554
Treatment of HIV Infection in Drug Users 554
Commonly Used Drugs 557
Heroin 557
Cocaine 557
Methamphetamine 558
Alcohol 558
Medication-Assisted Therapies 558
Medically supervised opioid withdrawal 558
Treatment of opioid dependence 559
Treatment for cocaine dependence 560
Treatment for methamphetamine dependence 560
Treatment for alcohol use disorders and alcoholism 560
Mental Illness and Illicit Drug Use 561
Drug Interactions with HIV Therapeutics 561
Special Issues in Prevention 564
Risk reduction 564
References 565
Chapter 41: The HIV-infected international traveler 568
Introduction 568
General Considerations 568
Vaccinations 570
Prophylaxis considerations 571
Selected Disease-specific Issues 571
Enteric infections 571
Etiologies of traveler's diarrhea (TD) in HIV-infected travelers 571
Prevention of TD in HIV-infected travelers 571
Treatment of TD in HIV-infected travelers 572
Respiratory infections 572
Bacterial pneumonia 572
Tuberculosis 572
Other respiratory infections 572
Emerging and re-emerging infections in HIV 572
Malaria 572
Leishmaniasis 573
Chagas disease 573
Other parasitic infections 573
Penicilliosis 574
Other endemic mycoses 574
Travel-Related Skin Disorders 574
Other Issues in the HIV-infected Traveler 574
New HIV infections 574
Fever in the returning HIV-infected traveler 575
Conclusion 575
References 575
Index 578