When to Start

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When to Start ARV Therapy in Adults
Part B Module B1 Session 2
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Objectives

• Discuss the rationale and timing for ART
  initiation, including the pros and cons of the
  different criteria.
• Describe the objectives of a clinical patient
  evaluation for ART initiation.
• Discuss the WHO clinical classification system
  and its use in deciding when to initiate ART.

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Rationale and Timing of ARV Initiation

• Typical course of HIV infection and progression
  of AIDS to death with and without ART
• When and how to start ARV therapy
• A patient needs ART only when symptomatic and/or
  there is evidence of significant immune system
  damage

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Rationale and Timing of ARV initiation,
continued

• Do not start ART if
• the patient is not motivated
• without intensive counseling
• if treatment cannot be continued
• patient has poor renal/hepatic function
• patient is asymptomatic and there is no CD4 data
• laboratory monitoring is not possible
• there is no access to diagnosis and treatment of
  OIs
• during an acute opportunistic infection
  (including TB)
• In the presence of terminal incurable disease,
  e.g. cerebral lymphoma

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Rationale and Timing of ARV initiation, continued

• How to start
• First-line therapy The simplest, cheapest,
  effective 3-drug combination
• Second-line therapy Select the next one or two
  combinations

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Clinical Evaluation for ART

• Elements of ART clinical evaluation
• Establish presence of HIV infection through
• history and physical exam
• voluntary counseling and testing (results from
  patients seeking a test while not hospitalized
  or seeking clinical care)
• counseling and testing (for diagnostic purposes)
• Establish status of HIV disease, e.g., which OIs
  are present
• Discuss the need for ARV therapy
• when to start and what to use
• Discuss adherence and other issues

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Clinical evaluation for ART, contnued

• Obtain basic laboratory support and establish
  baseline laboratory test results
• Absolute minimum tests HIV test hemoglobin or
  hematocrit level
• Basic tests WBC count Liver function tests
  (LFTs) and renal function tests (RFTs) blood
  sugar lymphocyte count
• Desirable tests CD4 amylase bilirubin lipids
• Optional Viral load

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Clinical evaluation for ART, continued

• Get a baseline medical history
• Psychosocial history
• Essential demographic characteristics
• Family economic status
• Family coping
• Length of time since diagnosis of HIV infection,
  current medications, and symptoms
• Past medical history including major illnesses
  (e.g., tuberculosis), hospitalizations, and
  surgeries, past medications and allergies
• For women, pregnancy history (gravida)current or
  planned pregnancy and access to contraceptive
  services

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Clinical evaluation for ART, continued

• Baseline physical exam
• Vital signs
• Weight and detailing of any abnormalities
  (including fundi if possible)
• Oropharynx
• Lymph nodes
• Lungs
• Heart
• Abdomen
• Extremities
• Nervous system
• Genital tract

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WHO Clinical Classification System
Stage I Asymptomatic, generalized
lymphadenopathy Stage II Weight loss lt10,
prurigo, fungal nail infection, herpes zoster,
recurrent URTIs Stage III Weight loss gt 10,
chronic diarrhea or fever, oral candidiasis/HL,
pulmonary TB, severe bacterial infections Stage
IV AIDS-defining illnesses e.g HIV wasting
syndrome, PCP, brain toxoplasmosis, candida
oesophagitis, extra-pulmonary TB, CMV retinitis,
Kaposis sarcoma, non-Hodgkins lymphoma and/or
performance score 4 bedridden gt50 of the day
during the last month
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WHO Clinical Classification System

• Adults When to start ART
• WHO stage IV disease (clinical AIDS) irrespective
  of CD4 cell count (CD4 cell count irrelevant)
• 2003 WHO guidelines for stage III use lt350 mm3
  in situation of rapid clinical decline
• WHO stages I or II, disease with a CD4 cell count
  lt200/mm3
• WHO stages II or III HIV disease lymphocyte
  count lt1200/mm3
• See Table 1 below Recommendations for
  Initiating ART
• in Adults and Adolescents with Documented HIV
  infection

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WHO Clinical Classification System, continued

• Children When to start ART (see Module 2,
  Session 3 for more details)
• lt18 months Stage III or stages I II disease
  CD4 lt 20)
• For children gt 18 months Stage III or stages I
  II disease CD4 lt 15. An assessment of viral
  load is not considered essential to start therapy

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NOTES on Table 1. Recommendations for Initiating
Antiretroviral Therapy in Adults and Adolescents
with Documented HIV Infection

• 1 The precise CD4 level above 200/mm3 at which
  to start ARV treatment has not been established
  but the presence of symptoms and the rate of CD4
  cell decline (if measurement available) should be
  factored into decision making
• 2 A total lymphocyte count of lt1000-1200/mm3 can
  be substituted for the CD4 count when the latter
  is unavailable and the HIV-related symptoms
  exist. It is less useful in the asymptomatic
  patient. Thus, in the absence of CD4 cell
  testing, asymptomatic HIV infected patients (WHO
  stage I) should not be treated because there is
  currently no other reliable marker available in
  severely resource constrained settings
• 3Treatment is also recommended for patients with
  advanced WHO Stage III disease including
  recurrent or persistent oral thrush and recurrent
  invasive bacterial infections irrespective of CD4
  cell or total lymphocyte count

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The WHO Clinical Staging System

• The WHO staging system includes a clinical
  classification system and a laboratory
  classification to categorize the
  immunosuppression of adults by their total
  lymphocyte counts
• This staging system has been proven reliable for
  predicting morbidity and mortality in infected
  adults
• The WHO Clinical Staging System is based on
  clinical markers believed to have prognostic
  significance resulting in four categories. It is
  helpful to incorporate a patient performance
  scale into the system.

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Clinical Stages

• Clinical Stage I
• Asymptomatic infection
• Persistent generalized lymphadenopathy (PGL)
• Performance scale 1 asymptomatic, normal
  activity

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Clinical Stage II

• Clinical Stage II
• Weight loss, lt10 of body weight
• Minor mucocutaneous manifestations (e.g.,
  seborrheic dermatitis, prurigo, fungal nail
  infections, oropharyngeal ulcerations, angular
  cheilitis)
• Herpes zoster, within the last five years
• Recurrent upper respiratory tract infections
  (e.g. bacterial sinusitis) 
• Performance scale 2 symptomatic, normal activity

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Clinical Stage III

• Clinical Stage III
• Weight loss, gt10 of body weight
• Unexplained chronic diarrhea, gt 1 month
• 9. Unexplained prolonged fever (intermittent or
  constant) gt1 month
• 10. Oral candidiasis (thrush)
• 11. Oral hairy leukoplakia
• 12. Pulmonary tuberculosis within the past year
• 13. Severe bacterial infections (e.g. pneumonia,
  pyomyositis)
• Performance scale 3
• bedridden lt50 of the day during the last month

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Clinical Stage IV

• Clinical Stage IV
• HIV wasting syndrome, as defined by the Centers
  for Disease Control
• 15. Pnemocystis carinii pneumonia (PCP)
• 16. Toxoplasma of the brain
• 17. Cryptosporidiosis with diarrhea gt1 month
• Cryptococcosis, extrapulmonary
• Cytomegaloviral disease of an organ other than
  the liver, spleen, or lymph node
• 20. Herpes simplex virus infection, mucocutaneous
  (gt1 month) or visceral (any duration)
• 21. Progressive multifocal leukoencephalopathy
  (PML)
• 22. Any disseminated endemic mycosis (e.g.
  histoplasmosis, coccidioidomycosis)

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Clinical Stage IV continued

• Clinical Stage IV, continued

• 23. Candidiasis of the esophagus, trachea,
  bronchi, and lungs
• 24. Atypical mycobacteriosis, disseminated
• 25. Non-typhoid Salmonella septicemia
• 26. Extrapulmonary tuberculosis
• 27. Lymphoma
• 28. Kaposis sarcoma (KS)
• HIV encephalopathy, as defined by the Centers for
  Disease Control
• Performance scale 4 bedridden gt50 of the
  day during last month

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WHO Improved Clinical Staging System

• A further refinement of the WHO clinical staging
  system includes a laboratory axis
• The laboratory axis subdivides each category into
  3 strata (A, B, C) depending on the number of CD4
  cells
• If this is not available, one can use total
  lymphocytes as an alternative marker

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WHO Improved Clinical Staging System, continued

• N.B. The reference values used for lymphocytes
  and CD4 count are based on data available from
  the developed world. There are indications that
  Africans may have a physiologically higher
  lymphocyte count. Projects with laboratory
  equipment to conduct lymphocyte counts in HIV
  patients should, if possible, collect data about
  lymphocyte counts and CD4 counts and correlate
  them with the disease stage.

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Thank You