TABLE OF CONTENTS

Abbreviations  .................................................................................................................................................. i

Acknowledgements  ......................................................................................................................................... v

Foreword  ........................................................................................................................................................ ix

The Needs-Based Approach to Persons with HIV infection  ........................................................................ I-1

Maximising Adherence to Antiretroviral Therapy  ........................................................................................ I-4

HIV Prevention in Care and Support Settings  .............................................................................................. I-7

Clinical Consultation Resources in the Caribbean  ........................................................................................ I-11

Appendix A: Sample Patient Adherence Risk Assessment Questionnaire  ..................................................... I-13

Appendix B: Epidemiology and Reporting of HIV/AIDS Cases in the Caribbean  ........................................ I-18

Appendix C: CAREC HIV/AIDS Case Definitions and Staging System  ........................................................ I-21

Appendix D: WHO Staging System for HIV Infection and Disease in

Adults and Adolescents  ................................................................................................................................. I-26

Common Dermatologic Manifestations of HIV Infection  ........................................................................... II-1
Common Oral and Dental Manifestations of HIV Infection  ....................................................................... II-6
Appendix A: Images of Common Manifestations of HIV Infection  ............................................................... II-13

OVERVIEW OF ANTIRETROVIRAL THERAPY (ART)....................................................................... IV-1
Highly Active Antiretroviral Therapy (HAART)....................................................................................... IV-1
Classes and Characteristics of ARVs........................................................................................................... IV-2
Principles of HAART: INITIAL THERAPY............................................................................................. IV-2
Timing of HAART Initiation....................................................................................................................... IV-2
Adherence.................................................................................................................................................... IV-4
Treatment of Co-Morbid Opportunistic Infections (OIs).......................................................................... IV-6
Laboratory Monitoring Prior to Initiation of HAART............................................................................... IV-6
Selection of the Initial HAART Regimen.................................................................................................... IV-6
Selection of Individual Agents in the HAART Regimen............................................................................. IV-8
Patient Follow-Up and Monitoring After Initiation of Therapy............................................................... IV-11
TREATMENT TOXICITY...................................................................................................................... IV-13
Treatment Failure: Clinical Definition........................................................................................................ IV-13
Treatment Failure: Immunological Definition............................................................................................. IV-14
Treatment Failure: Virologic Definition...................................................................................................... IV-14
SECOND-LINE AND SALVAGE ANTIRETROVIRAL THERAPY..................................................... IV-15
HIV Resistance to Antiretroviral Therapy................................................................................................. IV-15
Second-Line HAART Regimens................................................................................................................. IV-15
Salvage Therapy.......................................................................................................................................... IV-18
HAART CONSIDERATIONS FOR PATIENTS WITH CO-MORBID DISEASES.............................. IV-18
Patients with HIV and Tuberculosis (TB).................................................................................................. IV-18
Patients with HIV and Diabetes Mellitus................................................................................................... IV-19
Patients with HIV and Chronic Liver Disease............................................................................................ IV-19
Patients with HIV and Renal Disease......................................................................................................... IV-20
Patients with HIV and Other Sexually Transmitted Infections (STIs)....................................................... IV-20
Patients with HIV and Neuropsychiatric Disorders................................................................................... IV-20
METABOLIC COMPLICATIONS OF HAART AND HIV INFECTION............................................ IV-20
Lactic Acidosis/Hepatic Steatosis............................................................................................................... IV-20
Lipodystrophy............................................................................................................................................ IV-21
Hyperlipidaemia.......................................................................................................................................... IV-21
Insulin Resistance........................................................................................................................................ IV-21
Disorders of Bone Metabolism................................................................................................................... IV-22

TABLES
Table 1: General Recommendations of Initiation of HAART for HIV-Infected Adults and Adolescents.. IV-4
Table 2: Selected Factors that Influence Adherence..................................................................................... IV-5
Table 3: ARVs for Treatment of HIV Infection........................................................................................... IV-7
Table 4: Combination NRTI/NNRTI Tablets for Antiretroviral Therapy.................................................. IV-7
Table 5: Preferred Initial HAART Regimens............................................................................................... IV-9
Table 6: Alternative Initial HAART Regimens.......................................................................................... IV-10
Table 7: Common Adverse Drug Reactions Associated with First-Line HAART Regimens and Recommended
Drug Substitutions..................................................................................................................................... IV-12
Table 8: Second-Line Regimen Recommendations for Treatment Failure................................................. IV-17
Table 9: Drug Interactions with Tuberculosis Agents............................................................................... IV-18
Table 10: Selected Metabolic Complications in HIV................................................................................ IV-24
Table 11: Nucleoside Reverse Transcriptase Inhibitors (NRTIs)............................................................. IV-23
Table 12: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).................................................. IV-27
Table 13: Protease Inhibitors (PIs)............................................................................................................ IV-29
Table 14: Fusion Inhibitors........................................................................................................................ IV-36
Table 15: Interactions between PIs............................................................................................................ IV-37
Table 16: Interactions between PIs and NNRTIs..................................................................................... IV-39
Table 17: Drug Interactions between ARVs and Other Drugs.................................................................. IV-40
Table 18: Major Mutations Associated with Reduced Susceptibility to NRTIs..................................... IV-50
Table 19: Major Mutations Associated with Reduced Susceptibility to NNRTIs.................................. IV-50
Table 20: Major Mutations Associated with Reduced Susceptibility to PIs........................................... IV-51

Appendix A: CHARACTERISTICS OF ARVS...................................................................................... IV-23
Appendix B: DRUG-DRUG INTERACTIONS BETWEEN PIS AND NNRTIS................................. IV-37
Appendix C: DRUG INTERACTIONS BETWEEN ARVS AND OTHER DRUGS............................ IV-40
Appendix D: DRUGS THAT SHOULD NOT BE USED IN COMBINATION WITH
PIS OR NNRTIS DUE TO DANGEROUS DRUG INTERACTIONS..................................................................................................................................... IV-42
Appendix E: BASIC LABORATORY MONITORING FOR RECOMMENDED FIRST-LINE
REGIMENS.............................................................................................................................................. IV-45
Appendix F: HIV RESISTANCE............................................................................................................. IV-47
Introduction............................................................................................................................................... IV-47

Resistance to Nucleoside Reverse Transcriptase Inhibitors (NsRTIs) and Nucleotide Reverse
Transcriptase Inhibitors (NtRTIs)........................................................................................................... IV-47
Resistance to NNRTIs............................................................................................................................. IV-48
Resistance to PIs...................................................................................................................................... IV-48
Resistance Testing.................................................................................................................................... IV-48

The Effect of HAART on OIs and the Immune Reconstitution Syndrome  ................................................ V-1

Initiation of HAART for the Treatment-Naïve Patient in the Setting of an Acute OI  ................................ V-2

Management of Acute OIs in the Setting of Recently-Initiated HAART  ................................................... V-2

Treatment Recommendations: When to Initiate Therapy in the Setting of an Acute OI  ............................ V-3

Special Considerations in Pregnancy  ........................................................................................................... V-3

Disease-Specific Recommendations  ............................................................................................................ V-4

Appendix A: Summary of Pre-Clinical and Human Data on OI Drugs in Pregnancy  ................................ V-56

Appendix B: Treatment of AIDS-Associated OIs in Adults  .......................................................................... V-64

Appendix C: Dosage Adjustment in Renal Insufficiency  .............................................................................. V-83

Appendix D: Common Toxicities of Systemic Agents for Treatment of OIs  ................................................ V-86

Appendix E: Significant Pharmacokinetic Drug-Drug Interactions for Drugs in the

Treatment of OIs  ........................................................................................................................................ V-88

Prophylaxis to Prevent First Episode of Opportunistic Disease in Adults and

Adolescents with HIV Infection  ................................................................................................................ VI-1

Prophylaxis to Prevent Recurrence of Opportunistic Disease in Adults (After

Chemotherapy for Acute Disease) in Adults and Adolescents with HIV Infection  ................................. VI-6

Recommendations for Use Of Specific Vaccines In Individuals with HV Infection  ................................. VI-9

Prophylaxis to Prevent First Episode of Opportunistic Disease in Infants and Children

with HIV Infection  .................................................................................................................................... VI-14

Prophylaxis to Prevent Recurrence of Opportunistic Disease (After Chemotherapy for

Acute Disease) in Infants and Children with HIV Infection  .................................................................... VI-17

Criteria for Starting, Discontinuing, and Restarting OI Prophylaxis for Adults with

HIV Infection  ........................................................................................................................................... VI-19

Recommendations to Help Patients Avoid Exposure to or Infection with Opportunistic

Pathogens  ................................................................................................................................................. VI-21

Scenario A: Non-Pregnant Woman Who Needs ART for Her Own Health  ........................................... VII-5

Scenario B: Woman Who Is Already Receiving ART at the Time She Becomes Pregnant  .................... VII-6
Scenario C: Pregnant Woman, Not on HAART, Who Now Requires HAART for Her Own Health  ...................................................................................................................................................... VII-7

Scenario D: Pregnant Woman Who Does Not Require HAART for Her Own Health  ........................... VII-8

Scenario E: HIV-Infected Woman without Prenatal Care Who Presents in Labour  ................................ VII-9

Scenario F: Woman of Unknown HIV Status Who Presents in Labour.....................................................VII-9

Scenario G: Infants Born to Women Who Received No Antiretroviral Therapy for PMTCT Either
Prepartum or During Labour  .................................................................................................................. VII-10

Recommendations Regarding Breastfeeding  ......................................................................................... VIII-2

Recommendations for Management of Infants Born to Mothers with HIV Infection  ........................ VIII-3

Appendix A: WHO Clinical Case Definition for Pediatric AIDS  .......................................................... VIII-7

Appendix B: WHO Staging System for HIV Infection and Disease in Children  ................................... VIII-8

Appendix C: 1994 CDC Revised Human Immunodeficiency Virus Paediatric

Classification System: Clincal Categories  ........................................................................................... VIII-9

Appendix D: Interventions to Reduce the Risk of MTCT: Summary of the Evidence  .......................... VIII-11

Background  ........................................................................................................................................... IX-1

Diagnosis and Classification of Paediatric HIV/AIDS  ......................................................................... IX-1

OI Prophylaxis and Immunisations  ..................................................................................................... IX-1

Initiation of HAART in Paediatric Patients: General Considerations  ................................................. IX-2

Recommendations for Initiation of HAART in Resource-Constrained Settings: WHO

Guidelines  ............................................................................................................................................ IX-3

Recommendations for Initiation of HAART in Resource-Full Settings: NIH and CDC

Guidelines  ............................................................................................................................................ IX-6

Practical Considerations for the Caribbean  .......................................................................................... IX-7

Adherence  ............................................................................................................................................ IX-8

Recommended Initial Paediatric HAART Regimens  ........................................................................... IX-9

Second-Line and Salvage Antiretroviral Therapy  ................................................................................ IX-14

Paediatric Antiretroviral Therapy Drug Formulary for the Caribbean  ................................................ IX-17

Appendix A: Considerations on Specific Drugs  ................................................................................... IX-18

Appendix B: Currently Available ARVs for Paediatric Use  ................................................................. IX-20

Appendix C: Classification of Paediatric HIV/AIDS  ............................................................................ IX-46

 Appendix A: Recommendations for Treatment of OIs in HIV-Exposed and Infected

Caribbean Infants and Children  .......................................................................................................... X-34

Occupational exposure to HIV.............................................................................................................. XI-1
Risk of Transmission Associated with an Occupational Exposure....................................................... XI-1
Efficacy and Timing of PEP................................................................................................................... XI-1
Risks and Benefits of PEP..................................................................................................................... XI-2
PEP Regimens........................................................................................................................................ XI-2
Recommendations for Management of Occupational Exposures to HIV.............................................. XI-2
Follow-Up............................................................................................................................................. XI-3
PEP FOLLOWING SEXUAL EXPOSURE TO HIV.......................................................................... XI-4

PEP SCENARIOS AND RECOMMENDATIONS............................................................................ XI-5
Needlestick Involving HIV-Infected Source Patient.............................................................................. XI-5
Exposure Involving a Source Patient Whose HIV Status Is Not Known.............................................. XI-6
Exposed Healthcare Worker with a Positive Baseline HIV Test........................................................... XI-6
Exposure Involving Sexual Assault........................................................................................................ XI-7

TABLES
Table 1: Variables that Likely Increase Risk of HIV Transmission in Occupational Exposures...........XI-1
Table 2: PEP Management Recommendations: Percutaneous (Needlestick) Exposures...................... XI-3
Table 3: PEP Management Recommendations: Mucocutaneous or Non-Intact Skin Exposures......... XI-3
Table 4: Average Per-Exposure Risk Associated with Exposures to HIV........................................... XI-4

FIGURES
Figure 1: Recommendations for Antiretroviral Post-exposure Prophylaxis for Non-occupational
Exposure to HIV................................................................................................................................... XI-5