Ever since the launch of the WHO “3 by 5” initiative, which aimed to improve access to and use of health services supplying HIV care, the availability of antiretroviral treatment (ART) in sub-Saharan countries and elsewhere has dramatically increased.1 This scaling up should continue as access to treatment is recognized today as one of the key challenges for combining HIV care and prevention. Nevertheless, concerns have been raised about adherence to ART and its possible consequences, the most serious one being the acquisition of viral resistance that can threaten the effectiveness of ART and its long-term benefits for HIV-infected individuals.2 Previous studies have already highlighted a number of similar determinants of adherence to ART in low-medium and high-income countries, such as perceived side-effects or depression.3,4 However, if one takes into account the cultural and economic contexts, then a greater number of determinants may influence adherence to ART in HIV-infected individuals. For instance, it is known that for patients living in poor settings, financial and geographical difficulties in accessing treatment can impair adherence to ART.5 In addition, adherence is a dynamic process which changes over time and cannot be reliably predicted by a few time-varying patient characteristics.6,7 That is why access to ART needs to be accompanied by adapted methods helping patients adhere to ART. The findings from Shet et al8 in their recently designed mobile phone-based intervention in India showed that telecommunications technology in resource-limited settings may be used efficiently to enhance adherence to ART. In addition, a randomized controlled trial recently conducted in Kenya has shown the positive impact of receiving a short mobile phone message on adherence to ART.9,10
In Africa, few data exist about the possibility of using reminder methods to help patients maintain adherence to ART. We assessed correlates of adherence to ART and to what extent adherence could both vary during the follow-up of patients in care and be influenced by reminder methods.
A prospective cohort study was conducted in 9 rural district hospitals of the Centre region of Cameroon among HIV-infected patients enrolled from May 2006 to April 2008 in a randomized controlled trial designed to compare 2 monitoring strategies (ANRS 12110/ESTHER Stratall trial).11 Enrolled patients initiated ART at month 0 (M0). The schedule of subsequent clinical follow-up visits was as follows: day 15, month 1 (M1), and every 3 months thereafter until M24. Patients also answered a face-to-face questionnaire concerning their psychosocial and socioeconomic characteristics at M0, M1, M3, M6, M12, M18, and M24. We used a 10-point scale to measure the social level of patients, which has been already validated as a good predictor for health status.12 The behavioral section of the questionnaire included in particular information on patients' behaviors toward ART intake in terms of adherence, satisfaction with provided information on treatment, and on intake reminder methods. The variable entitled “reminder methods” was built through a question asking whether the patients used methods to remind them to take their treatment. If a patient reported having used a method such as “asking a person to remind him/her, setting a clock, mobile phone, or watch alarm,” then the use of reminders was identified. Methods other than these were labeled “other reminder method(s)”; and finally if no method was used, we considered the variable as “no reminder method”. A motivational variable was chosen to identify to what extent the patient showed a strong willingness to start HIV treatment. We chose a question, which explored whether the patient had started treatment through his/her own choice.
In the self-administered questionnaire, a section comprising seven questions was dedicated to the assessment of ART adherence. All ART-treated patients were asked to list, for each antiretroviral drug, the daily number of prescribed pills they had taken during the 4 days before the visit. Patients were also asked if they had “totally” or “partially” taken their prescribed doses of ART or had “interrupted their treatment” during the same 4-day period. Patients were considered “nonadherent” if they reported that they had taken less than 100% of the total dose of antiretroviral drugs prescribed and/or if they reported in the self-administered questionnaire that they had not “totally” followed their prescribed regimen during the 4 days before the visit. In addition, a visual analogue scale was used to reclassify as nonadherent those patients whose scale was <100%. An adherence level of 100% was indeed shown to be highly correlated with detectable serum concentrations of protease inhibitors by our group in France.13
The present study focuses on data collected after treatment initiation at M1, M3, and every 3 months thereafter for adherence to ART. Clinical data were collected only at enrollment (M0). The study population comprised 401 patients who had data on adherence to ART, accounting for 1970 clinic visits.
A mixed logistic regression model was used to identify the correlates of adherence to ART. Variables with a P value lower than 0.20 in the univariate analysis were included in the multivariate model. A forward stepwise procedure based on the likelihood ratio test was used to build the final multivariate model. The significance threshold was fixed at α = 0.05. Statistical analyses were performed using the SPSS v15.0 (SPSS, Inc, Chicago, IL) and Intercooled Stata 10 (StataCorp LP, College Station, TX) software packages.
Characteristics of the Study Population
Among the 401 patients, a total of 115 (29%) were men, and median [interquartile range (IQR)] age was 36 years (30-44). One-fifth reported being married and half had an education level higher than secondary school. The median (IQR) social level was 2[1-2]. At the enrollment visit, 267 (66%) patients reported having a mobile phone. The median (IQR) CD4 cell count was 193 (92-353), and one quarter of patients were at clinical stage 4. First-line regimens included stavudine, lamivudine, and nevirapine (n = 269, 68%); zidovudine, lamivudine, and nevirapine (n = 22, 6%); stavudine, lamivudine, and efavirenz (n = 72, 18%); or zidovudine, lamivudine, and efavirenz (n = 34, 9%).
Adherence to ART During Follow-Up
Patients reported adherence to ART in 1305 (66%) visits. A quarter (101) were considered adherent throughout the entire follow-up, whereas only 28 (7%) were nonadherent at each visit. The proportion of ART-adherent patients decreased from 73% at M1 to 61% at M24 (Fig. 1). With regard to the different reminder methods used to adhere to ART, patients reported having used a method in 92% of visits—including a person to remind them in 15% of visits and a programmed electronic device, such as an alarm clock, mobile phone, or watch, in 32% of visits.
Factors Associated With Adherence to ART
The results of both univariate and multivariate analyses are presented in Table 1. The univariate analysis shows a number of known correlates of nonadherence to ART, which are no longer associated in the multivariate analysis, such as being married and having a low social level. After the multivariate analysis, the following correlates remaining associated with adherence to ART were: being at HIV clinical stage 4, having reported no alcohol binge drinking, having a good perception of treatment and a higher satisfaction with information given by health providers. Interestingly, after having adjusted for all these correlates, we found that patients who had implemented some ART intake reminder methods, such as asking a person to remind him/her [odds ratio (OR) = 1.97, 95% confidence interval (CI): (1.21 to 3.23)], setting a clock, mobile phone, or watch alarm [OR = 2.45, 95% CI: (1.58 to 3.79)], or other methods [OR = 1.47, 95% CI: (0.97 to 2.23)] were more likely to be adherent to ART.
The main result of our study is that the use of reminder methods could help patients maintain adherence to ART, after adjustment for known confounders. The second issue raised by this analysis is the decrease in adherence to ART over time, highlighting the difficulties of maintaining adherence to ART from the early stages of treatment to the long-term phases.
Although studies on the use of electronic reminder devices in developed countries have demonstrated low effectiveness in maintaining adherence to ART,14 simplified electronic methods could be envisaged and introduced more effectively in the daily lives of patients, particularly in Africa. Indeed, studies conducted in other disease contexts have shown the positive impact of reminding interventions to help patients take medications. For instance, in asthmatic patients, receiving daily cell-phone text message reminders has shown to improve adherence to asthma treatment.15 In addition, in patients with antihypertensive therapy, the use of reminder devices has shown to have a positive impact on adherence.16 As far back as 2001, it was suggested that adherence strategies should take the “high-tech route” and that HIV could be monitored with the help of new devices.17 High-tech instruments have been perceived as “tools for thinking and tools for representing the world”, although more particularly, the cell phone is regarded as “the single most transformative technology for development”. Indeed, the use of mobile phones, computers, and the Internet has seen unprecedented development in Africa.18 Recent studies conducted in India have shown that the use of mobile phone reminders, using an automated call, and a picture message may be effective in sustaining adherence to ART in HIV-infected individuals.8,19 In our study, nearly two-thirds of patients possessed a mobile phone. As it has already been shown that the most common reason for missing doses is forgetting to take the drugs,20 using reminder methods such as an alarm clock, text, or call in resource-limited countries could be a tool to help patients taking long-term medications such as ART.21
The use of reminder methods could thus be promoted during HIV counseling as a relevant strategy to improve adherence to ART, and more interventions using available technologies in Africa need implementation after proper evaluation. Our study also highlights other correlates associated with adherence to ART, corroborating the findings of other studies in various contexts. One example of this is alcohol binge drinking which has been shown to have a very negative impact on adherence to ART.22,23 Identifying alcohol abuse in HIV-infected individuals should not be forgotten in the African context.24 Positive patient beliefs about ART efficacy and reduction of related side-effects and patient satisfaction with the information given by providers have also been found to help maintain adherence to ART. The findings in our study endorse those from previous observations suggesting the importance of providing relevant information and counseling from ART initiation and throughout follow-up.25
Some limitations have to be acknowledged. This study was not specifically designed to assess the impact of reminder methods on adherence to ART. We could have created a questionnaire, which focused in greater detail on this issue. However, as there is an important correlation between cognitive and motivational characteristics of the patients and the use of reminder methods, it was important to adjust the model for such confounders. Enough items were included in the self-administered questionnaire to avoid any such bias. Further implementation research studies should be designed to better investigate the effectiveness and the feasibility of including reminding strategies on adherence to ART. These findings could help care providers improve initiatives to maintain good adherence to ART, especially since HIV care decentralization in Cameroon has been enforced as a national policy and access to and coverage of ART are now recognized as effective tools in the prevention of sexual transmission of HIV.
We thank all members of the ANRS 12110/ESTHER Stratall study group. We especially thank all physicians and nurses who are involved in the follow-up of the cohort and all patients who took part in this study. Finally, we thank Jude Sweeney for the English revision and editing of our article.
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