Lower pill burden
is associated with higher rates of adherence to HIV treatment and better
virological outcomes, according to the results of a meta-analysis published in
the online edition of Clinical Infectious
Diseases. The research also showed that adherence was better with
once-daily regimens compared to twice-daily treatment, but once-daily therapy
did not have any advantages in terms of virological suppression.
burden was associated with both lower adherence and worse virologic suppression
in both twice-daily and once-daily subgroups,” comment the authors. “Adherence
was higher with once-daily ART [antiretroviral therapy] regimens than
twice-daily regimens…however, this difference was minimal and did not translate
into better treatment outcomes.”
The past decade
has witnessed important improvements in antiretroviral treatment. Overall,
drugs are now less toxic and better tolerated than in the past. Pill burden has also
been reduced and dosing schedules simplified. Two fixed-dose pills (Atripla and Stribild) are now available, providing potent HIV therapy in a single
A meta-analysis of
randomised trials published in 2009 showed that once-daily treatment was
associated with higher rates of adherence compared to twice-daily therapy, but
that rates of virologic suppression did not differ greatly between the
trials have been published since then. An international team of investigators
therefore re-visited the questions of whether pill burden and dosing schedule
have an impact on adherence and virologic suppression.
trials comparing once- and twice-daily therapy published or presented before 31
March 2013 were eligible for inclusion in the analysis. The study populations
could include people who had not taken treatment before (treatment naive); treatment-experienced people
switching treatment with an undetectable viral load; or treatment-experienced people switching treatment with detectable viraemia.
A total of 19
studies including 6312 people met the inclusion criteria. The studies were
conducted between 2004 and 2011. Most (18/19, 95%) were published in peer-reviewed
journals. Seven studies (37%) included treatment-naive patients, nine (47%)
monitored patients who switched treatment with an undetectable viral load and
three (16%) evaluated treatment-experienced individuals who changed treatment
when their viral load was detectable.
duration of follow-up was 48 weeks, and 17 studies (89%) reported on both
adherence and virologic suppression. The majority of studies (eleven, 58%) used
MEMS (Medication Event Monitoring System) to assess adherence. The remaining eight studies used pill count.
authors note that none of the studies included fixed-dose single pill
Higher pill burden
was associated with lower rates of adherence (p = 0.004). But when the results
were stratified by treatment strategy, the association between adherence and
pill burden was only significant for twice-daily combinations (p = 0.001).
There was also a
significant association between higher pill burden and reduced chances of
achieving virologic suppression (p < 0.0001). This was the case for both
once-daily (p = 0.005) and twice-daily (p = 0.0003) regimens.
Turning to dosing
schedule, adherence was higher with once-daily regimens compared to twice-daily
therapy (weighted mean difference [WMD] = 2.51%; 95% CI, 1.20%-3.83%, p =
0.0002). The adherence advantage of once-daily treatment was apparent in
treatment-naive individuals (WMD = 3.94%; 95% CI, 1.42%-6.47%, p = 0.0002), as
well as people switching therapy with detectable viraemia (WMD = 5.28%; 95%
CI, 0.60%-9.96%, p = 0.03) and also people who changed treatment with an
undetectable viral load (WMD = 0.95%; 95% CI, 0.36%-1.54%, p = 0.002). The
difference between these sub-groups was significant (p = 0.02).
did not differ significantly between once- and twice-daily regimens. The
investigators believe there are several possible explanations for this finding.
These include the relatively small difference in adherence rates between
once-and twice-daily regimens; the short period of follow-up in many studies;
and the high levels of adherence support provided in clinical trials. “For all
these reasons,” write the investigators, “the difference in virologic
suppression that we found between once- and twice-daily ART regimens may be
They conclude that
once-daily treatment is associated with better adherence, and that higher pill
burden is associated with poor virologic outcomes.
The authors believe
their findings are of significance to health systems which are looking at ways of
reducing costs. Single tablet HIV therapy and fixed-dose combinations are
marketed at a premium, but the investigators believe “separating out the
single-tablet regimens and or/fixed-dose combinations into their constituents
is not likely to have a major detrimental impact on virological outcomes
(provided that the overall pill burden does not increase dramatically).”