All HIV-positive people in Europe should be encouraged to start antiretroviral therapy if they have a CD4 cell count below 350, say new European HIV treatment guidelines launched this week at the European AIDS Clinical Society conference in Madrid.
The guidelines also state that the aim of any new therapeutic regimen should be to achieve a viral load below 50 copies/ml for the patient within six months - even for patients with extensive drug experience.
“The minimum goal of what needs to be achievable with salvage therapy is now an undetectable viral load,” said EACS President, Dr José Gatell.
The new European recommendations follow the arrival of two new classes of antiretroviral drugs, CCR5 inhibitors and integrase inhibitors, and evidence from clinical trials that undetectable viral load is now a realistic goal for the majority of highly treatment-experienced who include one of these drug classes in their new treatment regimen.
The revised guidance on when to start treatment follows a host of studies suggesting that earlier HIV treatment may be beneficial. At present guidance in the United Kingdom and some other European countries recommends that treatment should start before the CD4 cell count falls below 200. However a recent UK audit by the British HIV Association showed that 60% of patients had started treatment when their CD4 cell count was below 200, and one-third of these had been in care for more than six months.
The new guidelines are accompanied by two sets of new and equally bold guidelines on the management of metabolic conditions and of hepatitis B and C co-infection.
Acknowledging that the new set of guidelines were “much less conservative and more aggressive than the previous sets” in 2003 and 2005, Gatell said that the arrival of several new drugs, some from completely new classes, “will change substantially some aspects of antiretroviral therapy.”
HIV treatment guidelines
The guidelines state that the goal of any HIV therapy should be to achieve a viral load below 400 copies/ml within three months of initiation.
Amongst their other new recommendations are:
- Treatment is now firmly ´recommended´ rather than ´to be considered´ for all patients with a CD4 count under 350 cells/mm3. Patients with counts under 200 cells/mm3should be started on therapy ´without delay´.
- Viral load is largely discarded as an indicator for treatment; the guidelines merely state that treatment ´may be offered´ to patients with CD4 counts between 350 cells/mm3 and 500 cells/mm3 if the CD4 count has declined by more than 50 cells per year, if an individual has hepatitis C coinfection or if an individual is aged 55 or over. Treatment may also be recommended for patients in this CD4 cell band who have a viral load above 100,000 copies/ml.
- Combivir (AZT/3TC) is now relegated to an alternative rather than recommended nucleoside backbone.
- Truvada (tenofovir/FTC) and Kivexa (abacavir/3TC) are equally strongly recommended as NRTI backbones as long as the B*5701 test can be performed for abacavir hypersensitivity
- Boosted atazanavir (Reyataz) is only offered as an alternative boosted protease inhibitor, unlike fosamprenavir (Telzir), saquinavir (Invirase), or lopinavir/ritonavir (Kaletra), which are recommended for first-line therapy. This is because it is not yet licensed for use as a first-line therapy by the European regulators. But the guidelines say that “some physicians use atazanavir as a first line regimen” and, in an opening press conference, Gatell singled the drug out as an alternative to NNRTIs.
- Resistance testing must be performed for all patients at diagnosis and after treatment failure.
The guidelines are accompanied by two new sets of metabolic and hepatitis guidelines, all within a 52-page A6 booklet.
The metabolic guidelines detail:
- Screens needed for metabolic disorders and risk factors in new patients.
- Lifestyle and treatment interventions to prevent cardiovascular disease.
- Management of dyslipidemia.
- Recommendations for lipodystrophy; the guidelines here recommend avoidance of d4T (stavudine, Zerit) and AZT (zidovudine, Retrovir), and cosmetic face-fillers for lipoatrophy (although stating that the evidence base for their long-term benefits is lacking), but admit that there is no proven intervention that helps with fat accumulation other than exercise.
- Screening, lifestyle management and treatment for type II diabetes.
- Avoidance and treatment of hyperlactatemia.
- Risk management and treatment of high blood pressure.
Hepatitis treatment
The hepatitis guideline recommendations, amongst others, include:
- Hepatitis B treatment should be initiated in patients with viral DNA above 2000 international units per millilitre (IU/ml) and raised ALT levels.
- Telbivudine, with or without adefovir, should be used for patients without an immediate indication for HIV treatment.
- Truvada should be used in any antiretroviral regimen for patients who need it, due to the activity of tenofovir against hepatitis B.
- Hepatitis C treatment can be offered on the basis of a Fibroscan result and a biopsy is not necessary. Treatment should be deferred (except possibly in acute infection) if there is a fibrosis grade of zero or one.
- Currently the success rate for treatment of HCV genotype 1 at baseline viral loads of above 500,000 copies/ml is so poor that it may be better to defer treatment until more potent therapies can be identified.
- Treatment should be stopped if a 2 log10 (100-fold) reduction in HCV viral load is not achieved within 24 weeks
Treatment with pegylated interferon and ribavirin should be given for:
- 24 weeks with genotypes 2-3 and no detectable HCV RNA.
- Eight weeks with genotypes 2-3 with detectable HCV RNA or genotype 1 with undetectable HCV RNA.
- 72 weeks with genotype 1 and detectable HCV RNA
- Patients who have previously failed treatment should be given optimum support with antidepressants, painkillers and anti-anaemia drugs.
Gatell was challenged by questioners who remarked that the major crisis facing patients with HIV in Europe was not suboptimal therapy, but getting drugs at all. He commented that doctors were in a limited position to apply political pressure but that “the publication of a set of guidelines that say ´This is the minimum acceptable that you can do is very influential”. ´
Nikos Dedes of the European AIDS Treatment Group commented that there were ways for physicians and scientists to get involved in public policy via WHO or European Union meetings. “I would urge doctors to be more proactive,” he commented.
Download
The guidelines documents can be downloaded from the EACS website at http://www.eacs.eu/guide/index.htm