Novel NRTI backbone effective

Michael Carter
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This article is more than 22 years old.

Interim data from a two year HAART sequencing study has found that a novel NRTI backbone of abacavir and 3TC is particularly effective when combined with efavirenz.

Investigators from Duke University in the USA presented 48 week data from the 96 week CLASS study to the Barcelona AIDS conference. Trial participants were randomised to receive abacavir and 3TC with either the NNRTI efavirenz, the boosted protease inhibitor amprenavir/ritonavir, or a third NRTI, d4T.

About 300 people entered the trial, with an average viral load of 100,000 copies/mL and CD4 count of 300 cells/mm3.

Glossary

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.

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

first-line therapy

The regimen used when starting treatment for the first time.

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

efficacy

How well something works (in a research study). See also ‘effectiveness’.

At 48 weeks, 90% of people in the efavirenz arm had a viral load below 400 copies, against 81% in the triple NRTI arm and 80% in the boosted PI arm. When the number of people who had achieved a viral load below 50 copies was compared, the NNRTI arm was again seen to have the best results, with 93% of people with a viral load below 400 copies achieving a viral load below 50 copies against 75% for both the triple NRTI and boosted PI arms.

Whilst these data appear to favour the efavirenz-containing regimen, the differences observed were relatively small. There was no difference between the three arms if the trial in the amount of time it took for treatment to fail in those failing to maintain an undetectable viral load, suggesting that all three regimens have a place in first-line therapy.

The triple NRTI combination was best tolerated, and the boosted PI the least well, perhaps because of the use of ritonavir with amprenavir. As expected, central nervous system side-effects were reported by people in the efavirenz arm. An abacavir hypersensitivity reaction was experienced by 6% of people across all treatment arms.

Further trial data will be available in twelve months, including information on the longer term effectiveness of the three regimens, the response to switching and data on body shape changes and metabolic disorders. These results will be awaited with interested as it is hoped that the NRTI backbone of abacavir and 3TC will avoid the resistance and mitochondrial toxicity problems associated with long term use of AZT and d4T.

The study complements the Gilead 903 study also presented at the conference, which demonstrated the efficacy of another novel NRTI backbone - tenofovir and 3TC - thus increasing the range of options that can be employed in first line therapy.

References

Bartlett JA et al. Abacavir/lamivudine (ABC/3TC) in combination with efavirenz (NNRTI), amprenavir/ritonavir (PI) or stavudine (NRTI): CLASS preliminary 48 week results.Fourteenth International AIDS Conference, Barcelona 2002, abstract TuOrB1189.

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