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IDWeek 2013: Complera Works Well Regardless of Viral Load or CD4 Count, Improves Lipid Levels

The single-tablet regimen Complera (rilpivirine/tenofovir/emtricitabine) worked as well as Atripla (efavirenz/tenofovir/emtricitabine) for treatment-naive people across a range of viral load and CD4 T-cell levels, researchers reported at the Second IDWeek conference last week in San Francisco. Another study found that switching from a boosted protease inhibitor to Complera lowered cholesterol and triglyceride levels.

Calvin Cohen from the Community Research Initiative of New England reported findings from the open-label STaR trial, the first head-to-head comparison of Complera vs Atripla in people starting antiretroviral therapy (ART) for the first time.

Unlike the earlier ECHO and THRIVE trials, which compared the same drug combinations taken as separate pills plus placebos -- requiring multiple daily pills with different food requirements -- all participants in STaR took a single tablet once-daily.

The study included 786 participants. More than 90% were men, about two-thirds were white, one-quarter were black, and the median age was 36 years. The mean baseline CD4 count was approximately 390 cells/mm³. Two-thirds started treatment with a viral load at or below 100,000 copies/mL, about 27% had 100,000 to 500,000 copies/mL and about 7% had above 500,000 copies/mL.

Cohen reported results from a STaR sub-analysis looking at response rates according to baseline viral load and CD4 count.

Results

• Overall, both single-tablet regimens produced good virological suppression: 86% of participants in the Complera arm and 82% in the Atripla arm achieved undetectable viral load (<50 copies/mL) at 48 weeks in a snapshot analysis.
• Virological failure occurred in 8% and 6%, respectively, and CD4 gains were similar (200 vs 191 cells/mm³).
• Among people with <100,000 copies/mL at baseline, 89% taking Complera and 82% taking Atripla had undetectable viral load at week 48, a statistically significant difference.
• Among those with viral load >100,000 copies/mL, response was lower overall but similar for the 2 regimens, 80% vs 82%, respectively.
• Among people with >200 cells/mm³, response rates were 88% for Complera and 83% for Atripla (not a significant difference).
• Response rates were lower overall for people who started treatment with <200 cells/mm³ but similar for the 2 regimens, 72% and 71%.
• Turning to adherence as determined by pill counts, people with 95% or better adherence had high response rates with either Complera or Atripla: 90% and 88%, respectively.
• Response rates dropped among people with less than 95% adherence, to 75% and 66%, respectively, but neither difference between the 2 regimens was significant.
• Looking at these factors together, in an analysis that excluded patients with missing data, virological response rates were statistically similar among Complera and Atripla recipients with all combinations of baseline viral load, CD4 count, and adherence levels.
• Among people with the least favorable combination -- high viral load, low CD4 count, and sub-optimal adherence -- only 50% achieved viral suppression with either single-tablet regimen.
• Turning to virological failure, Complera appeared to fare a bit more poorly, especially among people with low CD4 counts; in the lower viral load/lower CD4, strata, 2 out of 10 people (20%) with excellent adherence and 3 out of 9 (33%) with lower adherence experienced virological failure on Complera, compared with none (0%) on Atripla.
• However, patterns were not consistent and the number of failing patients was small and affected by missing data, so differences were not significant.
• People with at least 95% adherence reported better tolerability on both regimens.
• In particular, highly adherent patients taking Atripla reported fewer efavirenz-associated central nervous system (CNS) side effects such as abnormal dreams or depression.

Cohen noted that this analysis was intended in part to see if rilpivirine is more vulnerable than efavirenz to resistance and treatment failure if patients miss doses. The findings indicated that although "both drugs suffered from missed doses," rilpivirine did not appear to do worse.

While rilpivirine has been associated with fewer CNS side effects in clinical trials, this sub-group analysis showed that the difference in tolerability was much less pronounced among people with CD4 counts above 200 and greater than 95% adherence, though the study could not determine the direction of cause and effect.

Lipid Improvements

Pablo Tebas from the University of Pennsylvania reported findings from the phase 3 SPIRIT study, which looked at outcomes among people with suppressed viral load who simplified treatment by switching from a ritonavir-boosted protease inhibitor plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) to Complera.

The study included 476 participants. About 90% were men, three-quarters were white, about 16% were black, the median age was just over 40 years, and they had been on ART for nearly 3 years. The mean CD4 count was high, approaching 600 cells/mm³. At baseline about one-third each were taking boosted atazanavir (Reyataz) and lopinavir/ritonavir (Kaletra), while 20% were on boosted darunavir (Prezista). For NRTIs, 81% used tenofovir/emtricitabine (the drugs in Truvada) and 13% used abacavir/lamivudine (the drugs in Epzicom). Participants were randomly assigned to switch to Complera either immediately or after 6 months.

Tebas' report focused on changes in blood lipids, which are known to affect cardiovascular risk. The researchers used the US National Cholesterol Education Program (NCEP) system, which classifies people as having desirable/optimal, borderline or high lipid levels based on their risk of developing cardiovascular disease.

Results

• Complera was shown to be non-inferior overall: 94% of participants who switched right away, 92% in the delayed switch arm, and 90% who stayed on their protease inhibitor regimen maintained virological suppression (<50 copies/mL) at 24 weeks.
• At 48 weeks, 89% in the immediate switch arm still had undetectable viral load.
• Total cholesterol levels fell by -25 mg/dL following either an immediate or delayed switch to Complera, while LDL "bad" cholesterol fell by about -16 mg/dL. HDL "good" cholesterol fell by only a small amount (-2 to -4 mg/dL).
• People who stayed on a protease inhibitor essential saw no change in any of these parameters.
• Triglyceride levels in the immediate switch arm fell by -54 mg/dL at 24 weeks and by -65 mg/dL at 48 weeks; the delayed switch arm saw a -81 mg/dL drop.
• In contrast, triglycerides rose slightly while patients remained on protease inhibitors (+3 mg/dL).
• These changes resulted in overall improvement in lipid profiles after switching to Complera.
• At baseline, 59% of participants were classified as having NCEP desirable total cholesterol levels; at 24 weeks, this rose to 84% in the immediate switch group while remaining about the same for people who remained on protease inhibitors. The before-and-after percentages were the same for triglycerides.
• The proportion of people with optimal LDL rose after the switch to Complera (from 29% to 45%), while the percentage with high HDL fell a bit (from 27% to 17%).
• This resulted in an increased proportion of switchers achieving a favorable total cholesterol-to-HDL ratio (from 41% to 55%), compared with no change (38% to 37%) among those continuing on protease inhibitors.

"Simplifying from a [protease inhibitor/ritonavir] regimen to [Complera] in HIV-1 RNA suppressed patients may be an effective therapeutic choice for maintaining virologic suppression...[and] improving lipid profiles," the researchers concluded.

10/11/13

References

C Cohen, D Wohl, K Henry, et al. STaR study: association of efficacy outcomes with baseline HIV-1 RNA and CD4 count and adherence rate for the single-tablet regimens rilpivirine/emtricitabine/tenofovir DF and efavirenz/emtricitabine/tenofovir DF in ART-naive adults. 2nd IDWeek Conference (IDWeek 2013). San Francisco. October 2-6, 2013. Abstract 671.

P Tebas, F Palella, P Ruane, et al. SPIRIT: simplification to rilpivirine/emtricitabine/tenofovir DF single-tablet regimen from boosted protease inhibitor maintains HIV-1 suppression and improves fasting lipids at week 48. 2nd IDWeek Conference (IDWeek 2013). San Francisco. October 2-6, 2013. Abstract 672.