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  EACS - 12th European AIDS Conference
November 11-14, 2009
Cologne, Germany
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Once-Daily Dosing Ups Risk of Stopping Antiretrovirals in Single-Clinic Study
  12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
Women, people with more antiretroviral side effects (especially jaundice and confusion), and people taking a once-daily regimen proved more likely to stop all their antiretrovirals for 1 or 2 days, according to results of a 903-person study at the HIV clinic of Rome's Catholic University [1]. Reasons for the correlation between once-daily dosing and unplanned drug holidays were not entirely clear from study results.
Since September 2007, Catholic University clinicians asked all outpatients taking antiretrovirals to complete a questionnaire on adherence and to rate 19 adverse symptoms of treatment on a scale of 0 to 4. The investigators summed individual symptom scores to create an overall score.
The 903 study participants included 593 men (66%). Median CD4 count stood at 540 and median viral load at 50 copies. One quarter of survey respondents had HCV infection, and 20% were injecting drug users. Most people (57%) were taking a protease inhibitor (PI) regimen, while 30% were taking a nonnucleoside-based combination, 10% were taking three nucleosides, and the rest were taking other combinations.
Of 885 people with dosing data, 396 (46%) were taking a once-daily regimen. Median treatment satisfaction score was 9 on a scale of 0 to 10, while the median score for belief in therapeutic efficacy was 9.5 on a scale of 0 to 10. A physical health score averaged 72.4 (out of 100), and a mental health score averaged 75.0 (out of 100).
Self-reported adherence on a scale of 0 to 100 was 80, and 17% of study participants had an adherence rating under 60. While 24.5% reported stopping all drugs for 24 hours in the past 2 months, 8% reported stopping for 48 hours. People taking a nonnucleoside regimen stopped drugs less than people taking other regimens. Multivariate analysis isolated several independent predictors of stopping all drugs for 24 or 48 hours:
Stopping antiretrovirals for 24 hours
· Female gender: odds ratio (OR) 1.80, 95% confidence interval (CI) 0.95-3.43, P = 0.07
· Once-daily regimen: OR 2.36, 95% CI 1.28-4.33, P = 0.004
· Higher side effect symptom score: OR 1.03, 95% CI 1.00-1.07, P = 0.02 Stopping antiretrovirals for 48 hours
· Female gender: OR 2.29, 95% CI 1.30-4.03, P = 0.004
· Once-daily regimen: OR 1.67, 95% CI 0.94-2.96, P = 0.08
· Higher side effect symptom score: OR 1.02, 95% CI 1.00-1.05, P = 0.08
Side effect symptoms scored by study participants were headache, fatigue, jaundice, stomach ache, nausea, diarrhea, constipation, abdominal bloating, confusion, sleep disturbance, cough, itching, muscle pain, hand or feet pain, anxiety, depression, fat accumulation, fat loss, and sexual dysfunction. Of these 19 problems, only jaundice and confusion independently raised the risk of stopping antiretrovirals for 24 hours: Jaundice upped the risk 30% (OR 1.30, 95% CI 1.03-1.63, P = 0.03), while confusion raised the risk 27% (OR 1.27, 95% CI 1.04-1.55, P = 0.02).
Despite the link between once-daily dosing and 1- to 2-day drug holidays, people taking once-a-day regimens did not have a higher rate of viremia above 50 copies (14% once daily versus 17% not once daily, P = 0.20), and they had a significantly lower rate of CD4 counts under 200 (2.1% once daily versus 5.7% not once daily, P = 0.008).
The investigators suggested that people taking once-daily combinations "may perceive therapy as a very easy task and be more prone to forgetfulness." But one can imagine other reasons for an independently higher risk of drug breaks in people taking their antiretrovirals once a day. The lower discontinuation rate with nonnucleosides than with other regimens, and the link between jaundice (a side effect of once-daily atazanavir) and drug breaks, suggest that concern about antiretroviral stigma contributed to treatment interruptions in some people. At the same time, physicians who suspect that certain people may be more prone to poor adherence could lean toward prescribing a once-daily regimen.
The long half-lives of drugs in some once-daily combinations may save brief holiday takers from viral rebounds and could contribute to the similar rates of detectable viremia with once-daily regimens and other regimens in this study. But getting into a drug-holiday habit cannot be good for long-term HIV control.
1. Murri I, Cingolani A, De Luca A, et al. Once-daily regimens were associated with a higher rate of self-chosen discontinuation. 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract PE10.1/7.