Bell DJ, Kapitao Y, Sikwese R, van Oosterhout JJ, Lalloo DG. Adherence to antiretroviral therapy in patients receiving free treatment from a government hospital in Blantyre, Malawi. J Acquir Immune Defic Syndr 2007 Aug 15;45(5):560-3.
To compare three methods of measuring adherence to antiretroviral therapy (ART) in HIV-infected adults receiving free treatment from a public hospital in urban Malawi.
A prospective cohort study.
Queen Elizabeth Hospital, the largest hospital in Malawi's largest city, Blantyre.
A sample of HIV-infected patients attended the clinic during the study period. Patients were receiving free ART, were aged 16 years and older, had been on Triomune for at least three months, self-administered their medication, and were mentally competent to give consent. Study participants were recruited between December 2005 and April 2006.
One hundred patients were approached, and 88 were enrolled into the study. On recruitment, participants were given a pill bottle closed with a MEMS (medication event monitoring system) cap (MC) that records the time and date whenever the bottle is opened. They looked similar but not identical to the usual Triomune® pill bottle. Each patient was prescribed 60 tablets of Triomune®. Patients were not informed of the MC function. Patients returned for their usual visit after four weeks, and the MC bottles were collected by the study nurse and MC data were read. Pill count (PC) on the remaining tablets was taken. An adherence questionnaire that included questions on whether the patient missed a pill and where the pills were kept was completed by patient (self-reporting).
The primary outcomes were MC and PC adherence percentages, calculated as the observed number of doses/the expected number of tablets taken, multiplied by 100. The association between MC and PC adherence was also analyzed.
Of the 88 participants who completed the study, four indicated that they kept their pills in a different bottle, and 4 MCs were found to be faulty, leaving 80 patients with MC data available for analysis. The mean age of study subjects was 38.6 years. Forty-six (57.5%) were female. Mean time on study was 28 days (range: 23-31 days). Among patients, 57.5% (n=46) had MC adherence percentages of >95%, and 16.2% (n=13) of <80%. Mean MC adherence rate was 88.1% and the median was 97.5% (range: 8.9%-100%). Mean MC adherence for men was 81.9% and 92.7% for women (p=0.19). PC adherence was significantly higher than MC adherence (p< 0.001). The mean PC adherence was 98.6% and the median was 100% (range: 87.5% -100%). There was no clear association between the adherence measured by PC and MC. No subject had PC adherence below 87%. By self-report questionnaire only, 23 patients admitted ever having missed tablets since starting ART. The mean MC adherence of these patients was 92.9%, compared with 86.2% in the 57 patients who denied having ever missed a tablet.
This study found poor correlation between an MC and a PC measure of adherence. In accordance with previous studies, the authors found a higher percentage of adherence by PC, compared with MC. MCs may underestimate or overestimate adherence because it cannot be determined whether the patient actually took a tablet every time the bottle was opened or took several pills when the bottle was opened. Self-reported adherence correlated poorly with MC data and provided the highest estimate of adherence. The authors note that the MC adherence levels found in this study suggest a potential for the development of resistance to antiretrovirals. Pill counting and self-reporting may be deficient as main measurements for adherence, although this study was unable to determine the degree to which MC underestimated adherence or PC overestimated it.
Authors believe that the study population was representative of the ART clinic patient population, since consecutive patients were enrolled, and none of the patients recruited were participating in any other clinical trials at the clinic.(1) Sample size was small, but 80 of 88 patients enrolled provided follow-up data. Adherence behavior could have been affected by the fact that patients were enrolled and monitored in the study for only one month, leading to an overestimation of their long-term adherence behavior.(1) One month is a short follow-up time, but most patients had been on ART for over a year prior to the study (median duration on ART 13.2 months, range: 3-63 months). The study lacked viral load and CD4 measurements to serve as a gold standard of adherence.
According to the authors, this is the first study to compare MC with standard adherence measures (PC and self-reporting) in a government ART clinic in Africa. The study results are in line with previous studies that showed pill counting to overestimate adherence compared with MC data.(2,3,4) PC and self-report are the main measures of adherence in many resource poor settings, but they may lead overly optimistic estimates of adherence.
A target of >95% adherence is often quoted as necessary for durable suppression of HIV viral load.(2) The study reported that it is probable that pill counting overestimates adherence, which raises concern about development of drug resistance. Currently, there are no practical alternatives to pill counting and self-reporting-the most commonly used measures of adherence, though they are acknowledged as deficient. Further studies should be performed in similar settings, in larger patient groups, and over longer periods of time. Improved methods to measure adherence to ART are also needed.
- Oyugi JH, Byakika-Tusiime J, Charlebois ED, Kityo C, Mugerwa R, Mugyenyi P, et al. Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting. J Acquir Immune Defic Syndr 2004 Aug 15;36(5):1100-2.
- Bangsberg DR, Charlebois ED, Grant RM, Holodniy M, Deeks SG, Perry S, et al. High levels of adherence do not prevent accumulation of HIV drug resistance mutations. AIDS 2003 Sep 5;17(13):1925-32.
- Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000 Jul 4;133(1):21-30. Erratum in: Ann Intern Med 2002 Feb 5;136(3):253.
- Harries AD, Nyangulu DS, Hargreaves NJ, Kaluwa O, Salaniponi FM. Preventing antiretroviral anarchy in sub-Saharan Africa. Lancet 2001 Aug 4;358(9279):410-4.