People on First HIV Protease Inhibitor May Not Need to Switch After Single Treatment Failure

People with HIV who experience a single episode of virological failure while on their first protease inhibitor can safely stay on the same regimen without risk of disease progression, according to a study described in the May 19, advance edition of Clinical Infectious Diseases.

Virological failure -- either inability to suppress HIV viral load below the limit of detection or the return of detectable virus while on antiretroviral therapy (ART) -- can have various causes including drug resistance and suboptimal adherence. Traditionally experts have recommended switching drugs if treatment failure occurs, but this may not always be necessary.

Yu Zheng from Harvard School of Public Health and colleagues looked at outcomes following virological failure among people on a first-line antiretroviral regimen containing a ritonavir-boosted protease inhibitor.

This retrospective analysis included 209 patients out of 1429 participants in 3 randomized AIDS Clinical Trials Group (ACTG) studies who experienced virological failure and had at least 24 weeks of follow-up thereafter. The trials evaluated the safety and efficacy of first-line ART containing lopinavir/ritonavir (Kaletra) or boosted atazanavir (Reyataz) plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

A majority of participants (about 60%) were men, most (83%) were enrolled in the U.S., and the median CD4 T-cell count was 118 cells/mm³. Virological failure was defined as incomplete HIV suppression 8 to 16 weeks after starting ART or viral rebound to >200-400 copies/mL after 24 to 32 weeks (definitions varied across the 3 studies). Three-quarters of participants achieved a viral load <400 copies/ml at least once before treatment failure.

Results

• The median time between ART initiation and virological failure was 39 weeks and the median viral load at the time of failure was 8000 copies/mL.
• Only 1 of the 209 participants had evidence of a treatment-emergent major protease inhibitor resistance mutation at the time of virological failure, though 4 did so at baseline.
• 15 patients (9%) had evidence of emergent NRTI resistance mutations at the time of failure, as did 23 people at baseline.
• The most common treatment approach after virological failure -- used by 66% of patients -- was to continue the same regimen.
• 64% of participants who stayed on the same regimen achieved viral suppression within 24 weeks after virological failure, compared with 72% of patients who changed regimens -- not a significant difference.
• Participants who remained on the same regimen had a significantly lower rate of NRTI resistance than those who switched (11% vs 30%, respectively).
• Rates of viral suppression were also similar for people who stayed on their regimen and those who switched among participants with no resistance mutations.
• Among participants who remained on their first-line regimen, factors significantly associated with subsequent viral suppression included achieving HIV RNA <400 copies/mL at any time before virological failure (odds ratio [OR] 3.39) and lower viral load at time of failure (OR 3.35 for <10 000 vs >10 000 copies/mL).
• Better adherence after virological failure was also associated with subsequent viral suppression (OR 0.38 for <100% vs 100% adherence).
• 75% of patients with 100% self-reported adherence achieved viral suppression after failure compared with 54% who reported adherence less than 100%.
• Among participants who switched -- which occurred a median of 10 weeks after treatment failure -- 71% achieved viral suppression within 24 weeks after changing their regimen.
• In this group, having viral load <400 copies/mL before virological failure predicted subsequent viral suppression.

"For participants failing first-line [ritonavir-boosted protease inhibitors] with no or limited drug resistance, remaining on the same regimen is a reasonable approach," the study authors concluded. "Our study suggests that a large proportion of patients failing these regimens can subsequently achieve virologic suppression without changing their ART regimen."

However, they added, "Improving adherence is important to subsequent treatment success."

7/10/14

Reference

Y Zheng, MD Hughes, S Lockman, et al. People on First HIV Protease Inhibitor May Not Need to Switch After Single Treatment Failure. Clinical Infectious Diseases. May 19, 2014 (Epub ahead of print).