Antiretroviral treatment that requires only a single
tablet taken once daily were associated with better viral suppression, higher adherence and lower likelihood of hospitalisation, researchers
reported at the 53rd
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this month
Modern antiretroviral therapy (ART) regimens are much
better tolerated and more convenient than early combinations that sometimes
required handfuls of pills to be taken multiple times a day. It is well known that
taking ART as directed most of the time leads to better viral suppression, and
studies generally find that lower pill burden is associated with better
adherence. But it is less clear whether taking one instead of two pills at a
time, or taking them once or twice daily, has a significant effect on treatment
adherence and outcomes.
Scott Sutton and colleagues from the Dorn Veterans Administration Medical Center and the University
of South Carolina compared viral suppression, medication adherence and hospitalisation
amongst US veterans taking single-tablet or multiple-tablet ART regimens.
This retrospective observational analysis used computerised medical and
pharmacy records from 15,602 patients who received HIV medications through the Veterans
Administration healthcare system between January 2006 and July 2012. Almost all
were men, nearly half were black, more than 40% were white and the average age
was 52 years. About two-thirds were diagnosed with mental health conditions and
40% with drug or alcohol use disorders.
Participants were categorised in the single-tablet regimen group if they
had ever received a one-pill-once-daily regimen at any time during the study period
(6191 participants, 40%); others were put in the multiple-tablet regimen group (9411
patients, 60%). Follow-up lasted at least two months without any switches after
starting a new regimen.
At baseline, people in the single-tablet and multiple-tablet groups had
similar CD4 cell counts (mean 432 cells/mm3). However, participants
prescribed a single-tablet regimen were less likely to have undetectable viral
load at baseline (42 vs 46%) and more likely to be treatment-naive (28 vs
Almost everyone in the single-tablet regimen group used Atripla
(efavirenz/tenofovir/emtricitabine), a recommended regimen in European and US
treatment guidelines. The other available one-pill regimens, Eviplera
(rilpivirine/tenofovir/emtricitabine) and Stribild
(elvitegravir/cobicistat/tenofovir/emtricitabine), were approved more recently in
the US (August 2011 and August 2012, respectively). All single-tablet
coformulations are marketed by Gilead Sciences, which provided support for the
Atripla and Eviplera include a NNRTI whilst Stribild includes an HIV integrase
inhibitor. There are currently no protease inhibitor-based single-tablet
regimens. More than two-thirds of participants in the multiple-tablet group
took protease inhibitors.
Treatment response rates were high overall
in both groups. But people taking a single-tablet regimen
were significantly more likely than those on multiple-tablet regimens to
achieve undetectable viral load during follow-up (64 vs 60%, respectively).
A significantly greater proportion of people in the single-tablet group
achieved at least 95% adherence (75 vs 56%) and at least 80% adherence (90 vs
78%), as determined by pharmacy claims data (medication
People taking a single-tablet regimen were significantly less likely to have
been hospitalised during follow-up compared with multiple-tablet recipients (27
vs 31%). They also took longer to be hospitalised and had fewer hospital stays (2.2
vs 2.7, respectively).
In a multivariate analysis controlling for other factors, people taking single-tablet
regimen were twice as likely to be at least 95% adherent to treatment (odds
ratio 1.98), were 31% less likely to be hospitalised (hazard ratio 0.69) and
had 45% fewer hospitalisations (incidence rate ratio 0.56).
"Patients on [single-tablet regimens] had better adherence compared to
those on [multiple-tablet regimens]" and had "reduced risk of
hospitalisations, fewer hospitalisations and longer time to hospitalisation",
the investigators concluded.
After the presentation, session moderator Pablo Tebas and others suggested
that the results may be affected by 'channelling bias'. This could include
preferentially prescribing boosted protease inhibitors for people with higher
baseline viral load or those judged less likely to be adherent, as these drugs
are generally more 'forgiving' of missed doses. Another example would be patients
with pre-existing kidney disease – a group more likely to be hospitalised –
not being put on tenofovir, which is included in all available single-tablet
"Healthcare providers and payers
may see a benefit in improved medication-taking behaviour with ART using a
single tablet compared to multiple tablets based on fewer hospital visits and
other improvements in clinical outcomes," the researchers suggested in a
press release issued by ICAAC. "These clinical outcomes could potentially
decrease total healthcare costs in HIV patients."
This suggestion is supported by other studies of US Medicaid participants
insured individuals which similarly
that people taking single-tablet regimens had fewer
hospitalisations than those taking multiple pills. Another
benefit in the US is that single-tablet
regimens require only one prescription co-pay.