Karcher H, Omondi A, Odera J, Kunz A, Harms G. Risk factors for treatment denial and loss to follow-up in an antiretroviral treatment cohort in Kenya. Trop Med Int Health 2007 May;12(5):687-94.
To evaluate risk factors for treatment denial and loss to follow-up in an antiretroviral treatment (ART) cohort in a rural African setting in western Kenya.
A prospective observational cohort study conducted between April 2004 and September 2005.
The outpatient clinic of Migori District Hospital, Nyanza Province, Kenya.
Treatment indication followed international guidelines and was considered if patients had CDC Stage C disease or two CD4 cell counts below 350 cells/µl. ART was provided as a component of a prevention of mother-to-child transmission of HIV (PMTCT) program. Eligibility for this study was defined as women who participated in the PMTCT program, their partners, and children. A total of 159 patients were enrolled.
There was no intervention. Pregnant women were screened as early as possible during pregnancy and, in case of a treatment indication, long-term therapy was started before delivery in order to minimize the risk of vertical HIV transmission. Patients were counseled thoroughly regarding benefits of therapy, possible side effects and the importance of adherence. All patients who met the criteria for treatment indication and who had received counseling were enrolled in the treatment program. Appointments for clinical and laboratory investigations were scheduled at baseline and at months 0.5, 1, 2, 4, 6, 9, 12, 15, and 18 after start of therapy. Clinical examination comprised staging of HIV infection and screening for concurrent diseases. Laboratory investigations consisted of blood tests; CD4 counts were evaluated at baseline and every six months thereafter. ART, supportive drugs, laboratory tests, and counseling were provided free of charge to patients. Adherence to ART was assessed by patient self-reports, visual analog scale, and pill counts at every visit.
The primary outcomes were treatment denial, death, and adherence.
RESULTS: Treatment denial: A total of 35 (22%) of the 159 enrolled participants failed to begin ART, of whom 20 were pregnant women, four died, and one had a severe psychiatric disorder resulting in treatment denial. The reasons for treatment denial were not identified for the remaining patients. In multivariate analysis, pregnancy [adjusted odds ratio (AOR) 3.60, 95% confidence interval (CI) 1.10-11.8; p=0.035] and lower level of education (AOR 3.80, 95% CI 1.14-12.7; p=0.03) were independently associated with treatment denial.
Treatment cohort: The median age of the 124 patients who started on ART was 31 years, 71% were females, 48% did not have an income-generating job, 52% had a secondary education, 71% were Luo ethnicity, 76% were Protestant, and 36% lived more than 30 km from the hospital. Before starting treatment, the median CD4 cell count was 189/µl (15-536/µl), and 46% of the participants had AIDS (CDC Stage C). Thirty (34%) of the 88 women were pregnant. The median treatment duration was nine months [interquartile range (IQR) 4-12 months]. The cumulative mean adherence after two months of therapy was 85%, and 69% of patients had adherence of more than 95%. The cumulative mean adherence after six months was 79%, and 63% had an adherence of more than 95%. The incidence rate of total loss to follow-up of patients under therapy was 43.2 per 100 person years (pys), the mortality rate was 19.2 per 100 pys, and the incidence rate of drop-out for other reasons was 24 per 100 pys. Death and drop-out because of other reasons occurred at a median of two months (IQR 1-3 months and 1-5 months, respectively). Older age [adjusted hazard ratio (AHR) 1.06, 95% CI 1.01-1.12; p=0.04], AIDS before starting treatment (AHR 5.83, 95% CI 1.15-29.5; p=0.03) and lower adherence after two months of treatment (AHR 1.05, 95% CI 1.03-1.07; p<0.001) were independent risk factors for death. Lower adherence also independently predicted drop-out because of other reasons (AHR 1.06, 95% CI 1.04-1.09; p<0.001).
The authors conclude that pregnancy and lower level of education are risk factors for treatment denial, while higher age, advanced AIDS stage, and impaired compliance to ART are risk factors for death. Adequate counseling strategies for patients with these characteristics could help to improve adherence and outcome of treatment programs in resource-limited settings.
Based on the Newcastle Ottawa rating system for observational cohort studies, this study was of adequate quality. The study had many limitations. First, the study size was small, at 124 participants. Second, since the study was originally part of a PMTCT program, the participants were more likely to be pregnant women and were therefore less representative of the overall population. Third, reasons for treatment denial were not available for most patients; therefore, it is possible that some causes for treatment denial were underreported. Fourth, the accuracy of the adherence measures in this study is unclear. Self-reported adherence is typically higher than more objective measures, such as unannounced pills counts, and the impact of incomplete adherence may have been exaggerated by defining adherence as 0% in the case of drop-out or death.
Treatment denial has been documented in several other studies. In Uganda and the Ivory Coast, 18% and 48%, respectively, of patients were reported to have refused to start ART.(1,2) Evaluation of PMTCT programs in Zambia, Ivory Coast, Uganda, and Tanzania showed that a lower level of education in pregnant women was associated with non-intake of ART.(3,4,5) Additionally, other studies in North America and Europe have shown associations between mortality and incomplete adherence, older age, and AIDS at initiation of therapy.(1,6,7,8,9,10,11) Furthermore, an association of incomplete adherence and subsequent treatment discontinuation was also demonstrated in studies from Europe and the United States.(12,13,14)
This study suggests many means through which more patients could be initiated and retained on ART, including improved pre-treatment counseling focusing on pregnant women and people of low education, improved adherence support during treatment, and treatment initiation prior to the development of AIDS. The findings of this study, however, should be interpreted with caution, given the many limitations noted above. Further, the effect sizes for older age and lower adherence on death and for lower adherence on drop-out are very small, although statistically significant. They are, however, intuitive and supported by other studies in the literature. Finally, the term "treatment denial" implies treatment was withheld from these patients. Given the various factors that contribute to the initiation of treatment, a less biased term, such as "failed treatment initiation," may be more appropriate.
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