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LAST UPDATE: Friday, 3 July, 1998 00:040 GMT   S U M M A R Y     S E S S I O N S    ...all the news, as it happens
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Summary of Wednesday, 1 July, 1998


On Wednesday, the International AIDS Society (IAS) presented the Treatment Guidelines for Antiretroviral Therapy 1998.


  • HIV viral load <20 copies/mL plasma is equivalent to approximately 105 copies in the human body.
  • RNA at 1 year of highly active antiretroviral therapy (HAART) is
    1. predictable RNA at 16 weeks; and
    2. very dependent upon adherence.
  • Bad news – patients fail therapy :
  • Difficulties with adherence (e.g. pill burden, side effects);
  • Resistance to drugs prior to therapy;
  • Therapy too weak (doomed to fail).
  • However, biological activity does not necessarily equal clinical efficacy.

Four questions remain at the centre of these treatment guidelines

  • When to initiate therapy?
  • Which drugs to begin with?
  • When to change therapy?
  • Which drugs to switch to?

Prior to initiation of therapy

  • Two plasma HIV-RNA measurements > 5,000-10,000 copies/mL;
  • Two CD4+ T cell counts;
  • If RNA remains at < 5,000-10,000 copies/mL and CD4 > 350-500, treatment may be deferred.

Which drugs to begin with?

  • Since the world AIDS meeting in Vancouver (1996), the options have increased substantially and include:
    1. PI + 2 nRTIs
    2. NNRTI + 2nRTIs
    3. 2 PIs +/- 1 or 2 nRTIs
    4. 1 PI + 1 NNRTI or an nRTI
    5. 3 nRTIs

Protease Inhibitor (PI); nucleoside reverse transcriptase inhibitor (nRTI); nonnucleoside reverse transcriptase inhibitor (NNRTI).

  • Several variables might be taken into account in choosing the initial regimen:
  • Evidence from clinical trials
  • Potency of drug regimen
  • Desire to preserve future treatment options (cf. risk of cross-resistance)
  • Drug-drug interactions
  • Side effects
  • Clinician familiarity with drugs
  • Cost/availability

When to change therapy?
The obvious answer is "when treatment fails," but what exactly is "treatment failure?"

  • Clinical failure
  • New symptoms;
  • Development of an opportunistic infection;
  • Toxicity/Intolerance.
  • Virological failure
  • Loss of control of viral replication (either detectable when previously undetectable or never becoming undetectable).
  • Reasons for treatment failure include (but are not limited to):
  • Toxicity;
  • Resistance (both genotypic and phenotypic);
  • Pharmacodynamic factors (i.e., Is the drug reaching its target?);
  • Adherence.

Controversy remains about whether to switch early or late. Logic might argue that delaying a switch might preserve treatment options – but no evidence really exists to prove the argument either way.

Which drugs to switch to?
The rules are:

  1. Confirm that failure has taken place;
  2. Avoid sequential monotherapy;
  3. Change 2 (and ideally ALL) drugs at one time;
  4. When recycling drugs, wait several cycles;
  5. Measure viral load regularly;
  6. Discuss all changes to schedule fully with patient;
  7. Define criteria for success and failure early on.

Treatment must be individualized based on clinical judgement about viral load, history of antiretroviral treatment, the patient’s response to treatment and the patient’s clinical history.

Effects of Antiretroviral Therapy
Increased drug use, increased costs and increased out-patient visits
Dramatically decreased inpatient bed use, reduced costs and mortality (since 3TC)

European median survival rates differ by region once CD4 < 50 cells/mm3

  • Southern Europe: 19 months
  • Northern Europe: 23 months
  • Central Europe: 40 months

These differences were accounted for by differential use of HAART

"Immune restoration disease"
Potent antiretroviral therapy may cause flare of clinically silent opportunistic infections, because of increasing inflammation at the site of organisms

CMV retinitis/encephalitis
Hepatitis C
herpes simplex virus
varicella zoster virus

Generally occurs within the first 8 weeks of therapy
Associated with low CD4 counts and no prophylaxis

Antiretroviral Treatment in Pregnancy
General principles

    1. antiretroviral treatment of mother
    2. prevention of HIV transmission to infant, especially at around birth
    3. combination antiretroviral therapy preferable to zidovudine monotherapy
    4. if on treatment, avoid therapy for 1st 12 weeks (with view of avoid any potential for foetal damage)

Treatment for the Rest of the World

  • Estimates of cost effectiveness of :
  1. opportunistic infection prophylaxis $370 per year of life saved
  2. dual RTI therapy $2,000 per year of life saved


  • Prophylaxis

Rifampicin/pyrazinamide 2/12 vs. INH 6-12/12

similar efficacy
adverse events similar (low in both)

adherence in Uganda was related to economic factors of patient

  • Diagnosis

less effective in hospitals without a microscope
resistance in northern Thailand:

Isoniazid 14%
Rifampicin. 13%
Multidrug resistant 8% (even higher in young adults)

  • Treatment

Ethambutol a safe effective substitute for thiacetazone (a common cause of severe hypersensitivity reactions)


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