CROI: Atazanavir/ritonavir joins other boosted PIs as potential single-class maintenance regimen

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Atazanavir/ritonavir (Reyataz / Norvir) appears to have similar effectiveness to lopinavir/ritonavir (Kaletra) or saquinavir (Invirase)/ritonavir when used as a maintenance regimen in patients who have already achieved undetectable viral load on standard triple combination therapy.

Susan Swindells of the University of Nebraska presented preliminary data from a pilot study of a simplified maintenance regimen using boosted atazanavir (Reyataz) monotherapy during a late-breaker session at the Thirteenth Conference on Retroviruses and Opportunistic Infections, held this week in Denver.

This prospective, open-label study (ACTG 5201) enrolled 36 HIV-positive participants who had achieved virological suppression (viral load below 50 copies/ml) for at least 48 weeks on a first antiretroviral regimen consisting of a protease inhibitor (PI) plus two nucleoside reverse transcriptase inhibitors (NRTIs).

Glossary

plasma

The fluid portion of the blood.

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.

monotherapy

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

treatment simplification

Making changes to an HIV treatment regimen to make medication adherence easier. Simplifying an HIV regimen can include reducing the number of antiretroviral (ARV) drugs in the regimen or changing to a combination ARV drug that provides a one-pill, once-daily complete regimen.

At study entry, participants switched from their current PI to ritonavir-boosted atazanavir (300mg/100mg). After six weeks, 34 patients discontinued their NRTIs (of the original 36, one withdrew consent and another experienced a disqualifying viral load increase). Viral load and plasma atazanavir concentrations were measured throughout the study, and drug resistance was assessed in cases of virological failure (defined as HIV RNA equal to or greater than 200 copies/ml).

Participants were followed for a median of 194 days (range 84-345). At week 24 after treatment simplification (discontinuation of NRTIs), 91% of patients maintained virological suppression (lower 90% confidence interval [CI] limit 85%). Three patients (about 9%) experienced virological failure, at 12, 14, and 20 weeks after simplification. Genotypic testing did not reveal any PI-resistance mutations in any of these three individuals. Two of these patients had no measurable atazanavir in their plasma samples at the time of virological failure. The third patient did have measurable plasma atazanavir at each visit, and achieved re-suppression to below 50 copies/ml while remaining on boosted atazanavir monotherapy. No participants discontinued therapy following treatment simplification due to adverse events.

References

Swindells S et al. A prospective, open-label, pilot trial of regimen simplification to atazanavir/ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression (ACTG 5201). Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 108LB, 2006.