ANTIRETROVIRAL THERAPY FOR HIV INFECTION

1
ANTIRETROVIRAL THERAPY FOR HIV INFECTION
2
AIDS deaths reach record level

• UNAIDS estimates that 2.6 million people will die
  from diseases related to HIV and AIDS during 1999
• 32.4 million adults and 1.2 million children
  living with HIV by the end of 1999
• In Mumbai, there were 4120 excess deaths during
  the period 1987-97, largely due to TB and other
  causes (which include AIDS)
• BMJ 1999 319 1387.
• Lancet 1999 354 1175-6.

3
The Human Immunodeficiency Virus
4
Transmission of HIV

• Sexual transmission.
• Transfusion of infected blood and blood products.
• Vertical transmission.
• Needle sharing among injecting drug users.
• Occupational exposure.

5
Markers of HIV Infection in S.E. Asia

• Fever for more than one months duration
• Weight loss of more than 10
• Diarrhoea of more than one months duration
• Mucocutaneous manifestations
• Generalised lymphadenopathy
• Extrapulmonary or disseminated and extensive
  pulmonary tuberculosis
• Recurrent pneumonia
• Ref. WHO 1998

6
Therapy For HIV Infection

• Inhibiting HIV replication with antiretroviral
  agents.
• Prophylaxis/treatment of opportunistic
  infections.
• Final objective is eradication of the virus.

7
ANTIRETROVIRAL AGENTS FOR HIV
8
Antiretroviral Agents

• Nucleoside reverse transcriptase inhibitors
  (NRTIs)e.g. zidovudine, stavudine, lamivudine,
  didanosine, zalcitabine, abacavir.
• Non-nucleoside reverse transcriptase inhibitors
  (NNRTIs) e.g. nevirapine, delavirdine, efavirenz.
• Nucleotide reverse transcriptase inhibitorse.g.
  Adefovir dipivoxil.
• Protease inhibitors (PIs)e.g. saquinavir,
  indinavir, ritonavir, nelfinavir, amprenavir.
• Others e.g. hydroxyurea, IL-2.

9
Principles of Antiretroviral Therapy

• Combination therapy is now recommended.
• Monitor disease progression by measuring HIV RNA
  and CD4 counts.
• Resistance develops very quickly.
• Drug interactions should be taken into
  consideration.
• Compliance should be monitored.
• Therapy should be initiated early.

10
Rationale for early initiation ofHighly Active
Antiretroviral Therapy (HAART)

• HIV replicates even during apparent quiescent
  phase
• Sustained viral suppression
• Slows immune system deterioration
• Reduces opportunistic infections
• Prolongs survival

11
When to Start Antiretroviral Therapy

• Initiate therapy if HIV RNA levelsabove 30,000
  copies/ml, irrespective of CD4 cell count
• CD4 cell counts below 350/ml irrespective of HIV
  RNA levels
• Both plasma HIV RNA levels in the 5000 - 30,000
  copies/ml range and CD4 cell counts between 350
  - 500/mL
• All patients with symptomatic established HIV
  infection
• International AIDS Society - USA Panel JAMA 2000
  283 381-90

12
STRONGLY RECOMMENDED INITIAL REGIMENSRegimens
are composed of one choice each from columns A
and B(Guidelines for the use of Antiretroviral
Agents in HIV-infected Adults and Adolescents,
Department of Health and Human Services, USA, Jan
2000)

• COLUMN B
• Stavudine Lamivudine
• Stavudine Didanosine
• Zidovudine Lamivudine
• Zidovudine Didanosine

• COLUMN A
• Efavirenz
• Indinavir
• Nelfinavir
• Ritonavir Saquinavir

13
When to change therapy

• Toxicity or intolerance to current regimen
• Difficulty with adherence to current regimen
• Virologic failure with current regimen
• International AIDS Society - USA Panel JAMA 2000
  283 381-90