Avoid Zerit, Trizivir in first-line treatment, new UK guidelines recommend

Keith Alcorn
Estimated reading time 3 minutes
This article is more than 22 years old.

2003 BHIVA draft treatment guidelines will advise against the use of d4T and of Trizivir in first-line therapy, Dr Duncan Churchill told the Ninth Annual Conference of the British HIV Association on Saturday in a preview of new British treatment guidelines.

He emphasised that the guidelines were still in draft form, and that comments were invited from UK clinicians and other interested parties.

The new guidelines suggest that d4T (stavudine) is to be avoided on the grounds of toxicity (principally lipoatrophy and peripheral neuropathy), whilst Trizivir alone is not recommended following the interim analysis of the ACTG 5095 study, which showed that Trizivir was less effective than the efavirenz-containing arms in the study. Previous guidelines had recommended that Trizivir be used only in patients with viral load below 100,000 copies/ml, but the new guidelines will highlight that interim analysis of ACTG 5095 showed a significantly higher failure rate in Trizivir-treated participants with viral load below 100,000 copies/ml when compared to the efavirenz-treated patients.

Glossary

first-line therapy

The regimen used when starting treatment for the first time.

naive

In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

lipoatrophy

Loss of body fat from specific areas of the body, especially from the face, arms, legs, and buttocks.

monotherapy

Taking a drug on its own, rather than in combination with other drugs.

The guidelines writing group has stopped short of taking a position on the question of which NNRTI to use in first-line therapy, but does maintain the emphasis on the convenience of NNRTI-based regimens when compared to protease inhibitors for first-line therapy.

The group also stops short of recommending tenofovir as a component of first-line therapy, despite noting that it may be an attractive option on the basis of 96 week preliminary data from the Gilead 903 study. However, tenofovir will be recommended for use with 3TC in patients with hepatitis B and HIV co-infection. The cost of tenofovir is likely to prove a consideration in its use as first-line therapy; London’s Chelsea and Westminster Hospital has already proscribed use of tenofovir in first-line therapy until its cost falls to a level similar to other nucleoside analogues, even before the drug is formally approved for first-line use.

T-20 (enfuvirtide) should be reserved for salvage use where at least one other active drug is available, and it is preferable that it should be used with two other active agents. Functional monotherapy (where T-20 is added to a failing regimen) is not recommended.

First-line protease inhibitor use should only be contemplated when the PI is boosted by ritonavir, say the guidelines group, implicitly suggesting that nelfinavir use in first-line therapy is no longer recommended.

The draft guidelines are due to be issued by the end of May and will be finalised during the summer, for final publication in October.

What is current practice in first-line treatment?

The 2002-3 BHIVA audit, which reviewed first-line regimens in 25 consecutive treatment-naïve patients at each participating centre, found that the most commonly prescribed regimens were:

  • Combivir/efavirenz (33%)

  • Combivir/nevirapine (21%)

  • Trizivir (9%) or Combivir/abacavir (2.5%)

  • Combivir/lopinavir (3%)

  • Combivir/nelfinavir (3%)
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