Sarna A, Luchters S, Giebel S, et al. Short- and long-term efficacy of modified directly observed antiretroviral treatment Mombasa, Kenya: A randomized trial. J Acquir Immune Defic Syndr 2008;48:611-19.
To determine whether a modified directly observed antiretroviral therapy (m-DOT) intervention would increase adherence to antiretroviral therapy (ART) in adults in the first 24 weeks after ART initiation. The secondary objective was to determine whether higher adherence rates would be sustained at 48-weeks post-intervention.
Randomized controlled trial. Eligible patients were block randomized to either the standard care (control) arm or the m-DOT (intervention) arm.
Four clinics and two hospitals in Mombasa, Kenya
Between September 2003 and November 2004, 234 adult (aged >18 years) HIV-infected patients were recruited from three outpatient HIV treatment clinics: a provincial referral hospital (n=167); a private, not-for-profit clinic (n=59); and a district hospital (n=8) in Mombasa, Kenya. Patients were eligible for participation if they were ART-naive, living in Mombasa, and eligible for ART (CD4 cell count <200 cells/mm3 or WHO clinical stage 3 or 4).
Participants in both study arms received first-line ART regimens consisting of single-formulation stavudine, lamivudine, and either nevirapine or efavirenz. As standard care, all patients attended three one-on-one adherence counseling sessions before initiating ART. Following initiation, participants visited treatment centers every 4 weeks for follow-up. The first two follow-up visits consisted of general adherence counseling and discussions of specific emerging problems with side effects or medication intake. Thereafter, counseling was tailored to the patients' individual needs.
In addition to standard care, patients in the intervention arm received m-DOT services twice weekly for the first 24 weeks of ART. Modified DOT, adapted from the tuberculosis directly observed treatment short course (TB-DOTS), promotes adherence by observing a proportion of a patient's drug taking. At each visit, patients in the intervention arm met with an m-DOT observer who observed ingestion of each patient's ART dose, inquired about difficulties encountered, and provided individualized adherence support. After cessation of m-DOT at week 24, patients ceased contact with m-DOT observation centers and received standard care.
Self-reported adherence was assessed every 8 weeks using structured questionnaires administered in Swahili by research assistants. Clinic-based pill counts were performed at each m-DOT visit and at every 4 weeks for controls. Secondary outcomes were HIV viral load, measured at 48 and 72 weeks; CD4 count at 24, 48, and 72 weeks; and body mass index (BMI), assessed monthly.
One hundred sixteen patients were randomized to the intervention arm and 118 were randomized to the control arm; 15 eligible patients declined to participate. Of the 234 people enrolled, 217 (92.75%) had a study endpoint at 24 weeks and 210 (89.7%) at 72 weeks. One hundred eighty-three participants completed the study and 27 died. Within the 24-week intervention period, 9.1% (9/99) of participants in the m-DOT arm self-reported missing doses compared with 19.1% (20/105) in the control arm (P=0.04); 96.5% (551/571) of the monthly pill-count measures (six data assessment points per patient) in the m-DOT arm showed adherence levels of >95% compared with 86.1% (445/517) of participants in the control arm (P<0.001). Analysis of other covariates within the 24-week intervention period showed that the adherence rate was higher among participants who lived with other people, had a pre-ART CD4 cell count above the median, and were aged 33-40 years compared with those aged less than 33 years. In multivariate analysis, patients in the m-DOT arm were 4.8 times (95% CI, 2.7 to 8.6; P<0.001) as likely to be adherent as controls in weeks 1-24. After m-DOT discontinuation, there were no statistically significant differences between the intervention and control arms in self-reported adherence at 48 or 72 weeks. CD4 counts did not differ between the groups at any time point. Body mass index had a larger mean increase at 24 weeks among m-DOT patients, but no difference was seen at 72 weeks. Viral load was undetectable at 48 weeks in a greater proportion of m-DOT patients, although the difference was not statistically significant (P=0.13) and was not sustained at 72 weeks. Viral suppression was more likely among depressed patients receiving m-DOT than non-depressed patients receiving m-DOT at week 48 (21/25 vs. 13/22; P=0.057) and week 72 (27/30 vs.15/23; P=0.027). No difference in survival at week 72 was observed.
The authors concluded that m-DOT was effective in increasing adherence to ART during the 24 weeks of the intervention, but the effects were not sustained after the cessation of the intervention and no long-term effects were observed on the secondary biological measures of CD4 count, HIV viral load, and BMI.
This clinical trial was of high quality. The method of randomization and allocation concealment was clearly described, as was attrition and loss to follow-up rates, which were low. The demographic characteristics of the two arms were similar at baseline, and analyses were adjusted to account for any differences. Additionally, as almost all eligible patients enrolled in the study, the likelihood of selection bias was minimal. Intraclient clustering of observations was correctly accounted for using generalized estimating equations in the statistical analyses.
Levels of ART adherence are generally greater in sub-Saharan Africa than in high-income countries.(1) A study in Haiti was the first conducted in a resource-limited setting to demonstrate that a home-based m-DOT strategy could effectively support adherence.(2) The findings of this study support those of a randomized controlled study that evaluated a peer-delivered m-DOT intervention in Mozambique and showed that although self-reported rates of adherence were higher among participants receiving the intervention, no differences were noted in immunological outcomes.(3) The results were consistent with other studies that showed a decline in adherence after the intervention was stopped.(4)
Although adherence rates declined to control-arm levels after cessation of the intervention, the results suggest that m-DOT may be a useful strategy to increase adherence levels among targeted sub-groups of ART patients at high risk for nonadherence. The optimal duration of m-DOT, however, still is not known.
- Mills EJ, Nachega JB, Bangsberg DR, et al. Adherence to HAART: a systematic review of developed and developing nation patient-reported barriers and facilitators. PLoS Med. 2006 Nov;3(11):e438. Review.
- Farmer P, Leandre F, Mukherjee J, et al. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy). Bull World Health Organ. 2001;79:1145-1151.
- Pearson CR, Micek M, Simoni JM, et al. Modified directly observed therapy to facilitate highly active antiretroviral therapy adherence in Beira, Mozambique. Development and implementation. J Acquir Immune Defic Syndr. 2006;43(Suppl 1):S134-S141.
- Simoni JM, Pearson CR, Pantalone DW, et al. Efficacy of interventions in improving highly active antiretroviral therapy adherence and HIV-1 RNA viral load. A meta-analytic review of randomized controlled trials. J Acquir Immune Defic Syndr. 2006; 43(Suppl 1): S23-S35.