Initial Treatment: Preferred Regimens

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Initial Antiretroviral TherapyA Case-Based
Panel Discussion
Donna E. Sweet, MDProfessor of
MedicineUniversity of Kansas School of Medicine
The International AIDS SocietyUSA
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Unmet HIV Health Care Need

• PLWHA age 15 to 49 years old in the U.S. eligible
  for ART in 2003 was 480,000.
• 340,000 were estimated to be diagnosed and in
  care.
• The proportion of persons in Adult/Adolescent
  Spectrum of HIV Disease eligible for ART was 67
• of these eligible persons 79 received ART.
• The estimated national number of persons who
  received ART in 2003 in this age group was
  268,000.

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Unmet HIV Health Care Need

• It is estimated that only 55 of eligible PLWHA
  age 15 to 49 years old are receiving ART in the
  United States

Estimated Number of HIV-infected Persons Eligible
for and Receiving HIV Antiretroviral Therapy,
2003--United States Eyasu Teshale, L
Kamimoto, N Harris, J Li, H Wang, and M McKenna
CDC, Atlanta, GA, USA (at 12th CROI)
DE Sweet, MD.Presented at RWCA Clinical Update,
August 2006.
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Initial Treatment Preferred Regimens
NNRTI-Based
pills/day
PI-Based

• Avoid in pregnant women and women with high
  pregnancy potential.

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Initial Treatment Alternative Regimens (1)
NNRTI-Based
pills/day

• Avoid in pregnant women and women with high
  pregnancy potential.
• Because of higher rates of hepatotoxicity,
  nevirapine should not be initiated in women with
  pre-nevirapine CD4 counts gt250cells/mm3 or men
  with CD4 T cell counts gt400 cells/mm3, unless
  the benefit clearly outweighs the risk.

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Initial Treatment Alternative Regimens (2)

PI-Based
pills/day
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Initial Treatment Alternative Regimens (3)

PI-Based
pills/day
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Initial Treatment Alternative Regimens (4)
NRTI-Based
pills/day
To be used only when a preferred or alternative
NNRTI- or PI-based regimen cannot or should not
be used as first-line therapy.
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Antiretroviral Components in Initial Therapy
NNRTIs

• ADVANTAGES
• Less dyslipidemia and fat maldistribution than in
  PI-based regimens
• PI options preserved for future use

• DISADVANTAGES
• Resistance - single mutation
• Cross-resistance among NNRTIs
• Rash hepatotoxicity
• Potential drug interactions (CYP450)

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Antiretroviral Components in Initial Therapy PIs

• ADVANTAGES
• Longest prospective data
• NNRTI options preserved for future use

• DISADVANTAGES
• Metabolic complications (fat maldistribution,
  dyslipidemia, insulin resistance)
• Greater potential for drug interactions (CYP450),
  especially with ritonavir

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Antiretroviral Components in Initial Therapy
NRTIs

• DISADVANTAGES
• Lactic acidosis and hepatic steatosis reported
  with most NRTIs (rare)
• Triple NRTI regimens show inferior virologic
  response compared with efavirenz- and
  indinavir-based regimens

• ADVANTAGES
• Established backbone of combination therapy
• Minimal drug interactions
• PI and NNRTI preserved for future use

Triple NRTI regimen of abacavir lamivudine
zidovudine to be used only when a preferred or
alternative NNRTI- or PI-based regimen cannot or
should not be used as first-line therapy.
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ART Goals Tools to Achieve Them

• Improvement of quality of life
• Reduction of HIV-related morbidity and mortality
• Restoration and/or preservation of immunologic
  function
• Maximal and durable suppression of viral load

• Selection of ARV regimen
• Preservation of future treatment options
• Rational sequencing of therapy
• Maximizing adherence
• Use of resistance testing in selected clinical
  settings

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Before Initiating ART

• Confirm HIV results
• Complete HP
• CBC, chemistry profile
• CD4 cell count
• Plasma HIV RNA measurement
• Resistance testing
• Assess readiness for treatment and adherence

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Considerations in Initiating ART Asymptomatic
HIV

• Willingness of patient to begin and the
  likelihood of adherence
• Degree of immunodeficiency (CD4 T cell count)
• Plasma HIV RNA
• Risk of disease progression
• Potential benefits and risks of therapy

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Considerations in Initiating ART Chronically
HIV-Infected Patient, Asymptomatic

• Strong evidence of decreased mortality and
  morbidity with ART if CD4 lt200 cells/µL or
  symptomatic
• Theoretical benefit of treatment at higher CD4
• Few data establish clinical benefit for treatment
  if CD4 gt200 cells/µL optimal point to initiate
  ART is unknown
• Individualize treatment decisions

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Current Antiretroviral Medications

• PI
• Amprenavir APV
• Atazanavir ATV
• Darunavir DRV
• Fosamprenavir FPV
• Indinavir IDV
• Lopinavir LPV
• Nelfinavir NFV
• Ritonavir RTV
• Saquinavir SQV
• hard gel HGC
• tablet INV
• Tipranavir TPV
• Fusion Inhibitor
• Enfuvirtide T-20

• NRTI
• Abacavir ABC
• Didanosine DDI
• Emtricitabine FTC
• Lamivudine 3TC
• Stavudine D4T
• Zidovudine ZDV
• Tenofovir TDF
• NNRTI
• Delavirdine DLV
• Efavirenz EFV
• Nevirapine NVP

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When to Start Treatment
DHHS Guidelines 4/7/2005
DE Sweet, MD.Presented at RWCA Clinical Update,
August 2006.
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The Use of Drug Resistance Testing
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Survival Benefits of AIDS Treatment in the United
States
Survival Benefits of AIDS Treatment, JID 2006194
(July 1)