In this study of participants recently diagnosed with HIV infection, once daily dosing of HAART resulted in higher adherence than twice daily dosing, as measured by a VAS. In contrast, among participants on once daily regimens, adherence to a one-pill regimen was no different than adherence to regimens with more than one pill. These results suggest that pill burden is not an important factor in determining adherence to contemporary once daily HAART regimens in HAART naïve patients.
Several studies have shown that participants exhibit higher adherence with once daily dosing of antiretrovirals compared to twice daily dosing.2,4,5,11
Some studies have also shown that a lower pill burden results in higher adherence.4–6
Specifically, Airoldi et al. found that patients who had a HIV-RNA <50 copies/mL on a more-than-one-pill once daily regimen and were then switched to fixed-dose combination EFV/FTC/TDF had better adherence after the switch (93.8% vs. 96.1%, respectively, p<0.01).7
To our knowledge, our study is the first to compare adherence between one-pill once daily regimens and more-than-one-pill once daily regimens in HAART-naïve patients. We expected that therapy with a single tablet once daily would result in higher adherence. Somewhat surprisingly, we found no differences in adherence between the once daily regimens. Our data support once daily dosing, but do not support the hypothesis that a one-pill once daily dose is associated with higher adherence than other once daily regimens.
Although our study participants who took HAART once daily had higher rates of virologic suppression compared to participants taking HAART twice daily, the difference was not statistically significant (p=0.15), though this result is likely due to our small sample size. Parienti et al. also found no significant difference in the proportion of subjects who achieved HIV RNA levels <50 copies/mL (p=0.21) between participants taking once daily versus twice daily regimens.2
Bangsberg et al. found that viral suppression was higher in participants taking fixed dose combination EFV/FTC/TDF (69%) compared to participants taking any other regimen (46%, p=0.02) but did not compare once daily versus twice daily regimens exclusively.6
We also did not find a statistically significant difference in achievement of virologic suppression based on pill burden, likely due to our small sample size. Bartlett et al. in 2001 found that a higher percentage of patients had an HIV RNA level <50 copies/mL at 48 weeks with lower pill burdens 12
. In 2006, Bartlett et al. found no difference in viral suppression based on pill count, likely due to the fact that their 2006 systematic overview included more potent HAART regimens compared to their overview in 2001.13
Bangsberg et al. found that viral suppression was higher in participants taking fixed dose combination EFV/FTC/TDF (69%) compared to participants taking any other regimen with more than pill (46%, p=0.02).6
Together, these results and the results of the present study suggest that pill burden for contemporary regimens is low enough that, among once-daily regimens, it is not a major factor in determining adherence or viral suppression as long as it is below some as yet undefined threshold.
This study has several limitations. Adherence was measured by self-report rather than more objective measures like pharmacy refill data or Medication Event Monitoring System (MEMS) caps. These data were available for a subset of participants, but not enough to produce reliable estimates for the questions addressed in the present set of analyses. As noted earlier, only 99 participants out of the entire Steps cohort of 184 contributed to the analysis, and only 76 out of 99 participants were included in the viral suppression analyses, thus decreasing our ability to detect small differences in adherence and virologic suppression. Some participants did not have a viral load in their medical record after starting HAART because they dropped out of or transferred care. The generalizibility of our results may be impacted by the fact that participants who were not prescribed HAART during the study, died, or were lost to follow-up are not included in these analyses, Also, adherence in participants was reported to be very high, which may not have been the case for the excluded participants. The high reported adherence is likely partly due to patients overstating their adherence, possibly due to social desirability. Finally, these data are observational, and participants should have been prescribed regimens that fit their lifestyle and clinical needs best. Patients thought to be less likely to adhere may have been placed on less demanding regimens from the start, thus confounding later adherence results. In that sense these data represent what is achievable in routine HIV care with contemporary HAART regimens.
AIDS Drug Assistance Programs (ADAPs) are state-run programs that provide HIV medications for low income, uninsured, and underinsured individuals in the United States. As ADAP client enrollment continues to increase, cost-cutting measures have had to be implemented. Each ADAP has adopted its own formulary, and 24 ADAPs do not cover all FDA-approved antiretrovirals in all drug classes.14
High drug costs are a concern in other developed and developing countries as well.15
Our study results suggest that fixed-dose combination pills are not as critical as dosing schedule in promoting excellent adherence. Cost containment strategies that rely on generic drugs not available in fixed-dose combination pills will, however, need careful evaluation for their clinical impact.
This is the first study to our knowledge to examine the effect of regimen factors on adherence in exclusively newly diagnosed, HAART-naïve participants on contemporary HAART regimens that include fixed dose combination EFV/FTC/TDF. We found that once daily dosing was associated with greater adherence than twice daily dosing. In contrast, the number of pills did not predict adherence among participants on a once daily regimen. When possible, once daily dosing may be the recommended dosing schedule, compared to twice daily dosing. Among once daily regimens, factors other than pill burden (e.g. side effects, drug interactions, daily schedule, and patient preference) should drive regimen selection.