AIDS 2014: Single-tablet HIV Regimens Not Necessarily More Durable

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Antiretroviral therapy (ART) regimens consisting of 1 pill taken once-daily -- known as single-tablet regimens -- were not associated with a longer time to treatment discontinuation when compared to some other modern, well-tolerated regimens that involve more pills or twice-daily dosing, according to a study presented at the 20th International AIDS Conference last month in Melbourne.

The development of single-tablet regimens (STRs) was a step forward in terms of convenience, and some studies suggest that they contribute to better adherence, which in turn promotes viral suppression. There are currently 4 STRs -- Atripla (efavirenz/tenofovir/emtricitabine), Complera (rilpivirine/tenofovir/ emtricitabine), Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine), and the newly approved Triumeq (dolutegravir/abacavir/lamivudine coformulation). Unlike early combination ART that could involve handfuls of pills taken up to 3 times daily, modern regimens typically consist of a few pills taken once or twice daily -- though some heavily treatment-experienced people with highly resistant virus still need multiple pills or even daily injections.

Nima Machouf and fellow investigators with the Canadian Observational Cohort (CANOC) Collaboration compared the duration of first-line single-tablet regimens to other recommended first-line regimens involving more pills or more frequent dosing.

This retrospective analysis included 2965 participants in the CANOC cohort who started ART between 2007 and 2012. More than 80% were men and the median age was 41 years. At baseline, 37% had high HIV viral load (>100,000 copies/mL) and 25% were coinfected with hepatitis C.

Atripla -- the only STR available for the entire study period -- was compared to 3 non-STR regimens containing 2 nucleoside/nucleotide reverse transcriptase inhibitors plus one of the following:

  • Raltegravir (Isentress) -- 3 pills taken twice-daily;
  • Ritonavir-boosted atazanavir (Reyataz) -- 3-4 pills taken once-daily;
  • Ritonavir-boosted darunavir (Prezista) -- 3-4 pills taken once-daily.

Nearly half of participants took Atripla, just over 40% took atazanavir, 7% took darunavir, and 3% took raltegravir. Single-tablet regimen recipients were significantly more likely than non-STR recipients to be men (87% vs 81%, respectively), but less likely to have high viral load (33% vs 40%) or a CD4 T-cell count below 200 cells/mm3 (27% vs 37%).

The primary study outcome was time to discontinuation of the first-line regimen.

Results

  • Overall, 1449 participants (49%) discontinued their first regimen during a median follow-up period of 2.5 years.
  • People taking a non-STR regimen containing boosted atazanavir were significantly more likely than Atripla recipients to discontinue treatment, after adjusting for demographics, baseline viral load and CD4 count, and calendar year and study site (adjusted hazard ratio 1.16, or 16% more likely).
  • In contrast, people taking a non-STR regimen containing raltegravir were less likely to discontinue treatment (adjusted hazard ratio 0.58, or 42% less likely).
  • There was no difference in likelihood of discontinuation for people taking a non-STR regimen containing darunavir (hazard ratio 1.01).
  • Comparing Atripla to all 3 non-STR regimens combined, the adjusted hazard ratio was 0.80, or 20% less likely to discontinue.

"[An] STR regimen does not necessarily result in a more durable treatment," the researchers concluded. "Even with a higher pill burden and twice daily dosing, patients who initiate treatment with [a] raltegravir or darunavir/ritonavir based regimen had a similar rate of discontinuation of the first-line regimen compared to patients on an STR."

8/22/14

Reference

N Machouf, L Szadkowski, B Trottier, et al. Do single tablet regimens translate into more durable HIV treatments? Evidence from the Canadian observational cohort (CANOC Collaboration). Abstract WEPDB0103.