Factors affecting antiretroviral treatment adherence among people living with human immunodeficiency virus/acquired immunodeficiency syndrome: A prospective study.

CONTEXT: Antiretroviral adherence is the second strongest predictor of progression to acquired immunodeficiency syndrome (AIDS) and death, after CD4 count. Adherence to antiretroviral therapy (ART) has been strongly correlated with human immunodeficiency virus (HIV) viral suppression, reduced rates of resistance, an increase in survival, and improved quality of life. AIMS: To determine the adherence rates and factors affecting adherence to ART among people living with HIV/AIDS (PLWHA). SETTINGS AND
DESIGN: A Prospective study for 1 year was conducted among PLWHA, aged between 15 and 49 years, visiting ART center. SUBJECTS AND METHODS: 242 PLWHAs were included in the study. Structured questionnaire was used to obtain data on sociodemographic profile, factors affecting adherence. Adherence was assessed through self-reports, routine and random pill counts, and assessment of medical records. STATISTICAL ANALYSIS USED: Descriptive statistics, logistic regression, and Chi-square tests were computed using Epi Info 7 version CDC (Centers for Disease Control and Prevention) U.S. Department of Health and Human Services.
RESULTS: Adherence to ART was finally assessed on 242 PLWHAs. Mean age of subjects was 35 ± 7.8 years. One hundred percent adherence rate (consistent adherers) for the whole 6 month period was seen only in 31.6% patients. Lower 6 month averages of 95-100%, 80-95%, and <80% were noted in 49.8%, 9.1%, and 9.5% patients, thus resulting in optimal adherence rate of >95% in 81.4%. Earning member (odds ratio [OR] =0.404) and weight difference (OR = 0.818) were most associated with the adherent individuals. Most common psychological reason was forgetfulness in 44.9%.
CONCLUSIONS: Adherence rate was poor among PLWHA and economic factors play an important role in adherence.

Introduction

Human Immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has evolved as a major global public health problem with social and economic repercussions assuming pandemic proportions.[1] Its estimated globally more than 71 million were infected with HIV as on December 2014, and nearly 36.9 million people were living with HIV/AIDS worldwide. Approximately, 4 million in the low- and middle-income countries were receiving antiretroviral therapy (ART).[2] There has been a no[table 10]-fold increase in these figures over the last 5 years.[3]

India carries the world's third largest burden of HIV after South Africa and Nigeria with an estimated 2.27 million people between the ages of 15–49 years being affected constituting 88.7% of the total estimated number of people living with HIV/AIDS (PLWHA).[45]

The goals of ART include prolongation of lifespan and improvement in quality of life, reduction of viral load and subsequent reduction of HIV transmission, and quantitative and qualitative immune reconstitution.[6] To achieve desired outcomes, HIV/AIDS patients are required to have more than 95% adherence to ART. Antiretroviral adherence is the second strongest predictor of progression to AIDS and death, after CD4 count.[78]

Failure to adhere could be due to multiple factors including late detection, stigma and discrimination, and difficulty in accessing health facilities, adverse effects of drugs, comorbidities, psychosocial factors, economic constraints, and availability of ART facilities.[9] Adherence to ART being an important determinant of clinical and nonclinical outcomes, it is necessary to identify the factors that influence it both positively and negatively. This knowledge would help in planning and executing individualized management plans and community level interventions to ensure optimal results. Primary care physicians can utilize these factors related to adherence in the management of HIV. This can help them in improving the adherence rates among people infected with HIV/AIDS. This can help in managing the HIV/AIDS patients as any other chronic illness such as diabetes and hypertension.

This study was done to determine adherence rates and factors affecting adherence of ART among PLWHA.

Subjects and Methods

The study was carried out at ART centers in North Karnataka, India for a period of 1 year. People living with HIV/AIDS (PLWHA) aged between 15 and 49 years were recruited. Severely ill or HIV with complications (TB, hepatitis, etc.) were excluded from the study. Sample size of 242 was estimated using the adherence rates for ≥95% of doses at ART center as 83% from the study by Machtinger and Bangsberg.[7] Formula used for sample size was N = 4PQ/L2, 95% confidence limits and 6% permissible error and 5% attrition rate was presumed for sample size estimation.

PLWHA attending the ART center was sequentially approached on selected days during the study period. The first 242 patients who satisfied the inclusion criteria and consented to participate were included in the study. The study was approved by the Institutional Ethical Committee and written informed consent was obtained from all participants before the enrollment into the study. A structured questionnaire was used to obtain data on sociodemographic profile, factors affecting adherence, and laboratory investigations. Adherence was assessed through self-reports, routine and random pill counts, and assessment of medical records.

Statistical analysis

Data were analyzed using Epi Info Version 7 CDC (Centers for Disease Control and Prevention) U.S. Department of Health and Human Services. Descriptive statistics such as frequencies, proportions for qualitative data, and mean and standard deviation (SD) for quantitative data were computed. Chi-square test and t-test were the test of significance for qualitative and quantitative data, respectively. Multiple logistic regression was computed to identify the factors affecting adherence. P < 0.05 was considered statistically significant.

Adherence rate was calculated according to the following formula.

Results

Adherence on ART was finally assessed on 242 PLWHAs, mean age of subjects was 35 ± 7.8 years. Majority (59.5%) of them were in the age group 25–39 years, with female preponderance (55%). Higher education status was observed among males. Majority of the participants were Hindus (85.5%), residing in rural areas (62%) and were unskilled laborers (64.9%). Nearly half were from a poor socioeconomic background, and 35.1% were below poverty line. About 63.3% of males had multiple sexual partners (χ2 = 76.62, P < 0.0001). HIV-1 was predominant type in 94.6% and HIV-2 in 5.4%. Most common route of transmission was heterosexual (88.8%) and majority (53.7%) were initiated on ART within 6 months of diagnosis of HIV [Table 1].

Table 1

Distribution of people living with human immunodeficiency virus/acquired immunodeficiency syndrome according to different study characteristics

Zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) regimen (Regimen 1) was the most common regimen initiated in 54.1% patients followed by stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP) regimen (Regimen 2) in 43.8% patients. There was a significant preference for the stavudine (d4T) + lamivudine (3TC) + nevirapine (NVP) regimen in females, whereas zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) regimen was preferred in males (χ2 = 37.833, P < 0.001).

Majority of the patients (66.1%) had CD4 counts <200 cells/mm3 at initiation of ART. At the end of 6 months of treatment, a significant improvement in CD4 counts was noted (t = 20.181, P < 0.001); 85% had CD4 counts >200 cells/mm3. Significant improvement in weight was also observed among subjects on ART (t = 9.636 P < 0.001).

Treatment adherence

One hundred percent adherence (no doses missed) was noted in 81.8% patients at the end of 1 month, which dipped to 66.5% patients by the end of the 2nd month. However, a gradual increase was noted over the remaining 4 months: 70.8%, 72.2%, 76.9%, and 84% at the end of the 3rd, 4th, 5th, and 6th months, respectively [Table 2].

Table 2

Distribution of patients according to adherence percentages at the end of each month and 6 months average

A 100% adherence rate (consistent adherers) for the whole 6 month period was seen only in 31.6% patients. Lower 6 month averages of 95–100%, 80–95%, and <80% were noted in 49.8%, 9.1%, and 9.5% patients, thus providing an optimal adherence rate of >95% in 81.4%.

The adherence rates in females were higher than in males but were not statistically significant (χ2 = 3.429 P = 0.064). There was no significant difference in adherence rates between the stavudine and zidovudine regimens or in the occurrence of adverse effects in adherent and nonadherent groups.

Univariate logistic model was followed by multivariable logistic model. P < 0.1 was considered statistically significant in the univariate model, and those significant variables were included in the multivariable model. Backward method was used, in which AIC and BIC values were used to compare the best-fitted model.

Earning member (odds ratio [OR] =0.404) and weight difference (OR = 0.818) were most associated with the adherent individuals. Economic factors and improvement in weight played an important role in adherence among HIV patients. No other factor significantly affected adherence rate [Table 3].

Table 3

Multiple logistic regression to find out the factors playing a role in adherence

Missed doses

The mean number of doses missed over the period of 6 months was 21.7 (SD = 52.3). The total number of missed doses had negative correlations with improvements in CD4 counts (P = 0.038*) and weight (P < 0.001), i.e., with an increase in missed doses, there was a decrease in CD4 count and weight. One hundred and fifty-eight (68.4%) patients had missed at least 1 dose during the 6 months period. Multiple reasons that were cited for the same are shown in Table 4. Most common psychological reason was forgetfulness in 44.9%, socioeconomic reason was a loss of hours of job in 9% and adverse effect.

Table 4

Reasons for missing doses*

Discussion

In this study, it was observed that HIV was predominant in young, rural, economically, and educationally challenged subjects, indicating the need for awareness and improvement in social standards among this population. Higher prevalence of multiple sexual partners in males points toward the need for emphasizing safe sexual practices. Similar observations were made by other studies worldwide.

One hundred percent adherence rate (consistent adherers) for the whole 6 month period was seen only in 31.6% patients. One hundred percent adherence was noted in 81.8% patients at the end of 1 month, which dipped to 66.5% patients by the end of the 2nd month. However, a gradual increase was noted over the remaining 4 months: 70.8%, 72.2%, 76.9%, and 84% at the end of the 3rd, 4th, 5th, and 6th months, respectively.

About 94.3% adherence at baseline and 91.3% adherence at 3 months were observed in the study by Amberbir et al., the principal reasons reported for skipping doses in this study were simply forgetting, feeling sick or ill, being busy, and running out of medication in more than 75% of the cases similar to the present study.[10] In the study by Safren et al. in Chennai observed 74.3% adherence at 6 months, and in the study by Shah et al. in Mumbai observed 73% adherence.[1112] The self-reported adherence rate of the patient on ART was 81.1% in the study by Belayihun and Negus.[13]

Forgetfulness, depression, and fear of disclosure were the most common psychological reasons for missed doses among subjects, constituting about 90% of reasons in the present study. According to the study by Wanchu et al., the major reasons for nonadherence were financial constraints, forgetting to take the medication, drug toxicity, and lack of access to the drug, fear of getting immune to the benefit of the drug, and to avoid adverse effects.[14] This is in accordance with the present study except for the financial constraints in the present study as the ART drugs are supplied free. In CARES study, the most frequently reported reasons for missing doses were forgetfulness, being busy, and antiretroviral drug side effects similar to the present study.[15] In the Vancouver Injection Drug Users Study (VIDUS) by Kerr et al., forgetting was the most frequently cited reason (27%) for missing doses of HAART in accordance with the present study.[16]

In the present study, earning member (OR = 0.404) and weight difference (OR = 0.818) were most associated with the adherent individuals. No other factor significantly affected the adherence rate among PLWHA.

Byakika-Tusiime et al., in their study in Kampala, Uganda, found that factors associated with nonadherence were marital status (OR = 2.93, 95% confidence interval [CI]: 1.32–6.50) and low monthly income <50 US dollar; (OR = 2.77, 95% CI: 1.64–4.67).[17] In the study by Amberbir et al., patients who were not depressed were two times more likely to be adherent than those who were depressed (OR: 2.13, 95% CI: 1.18, 3.81). However, at the follow-up visit, social support (OR: 2.42, 95%CI: 1.29, 4.55) and the use of memory aids (OR, 3.29, 95% CI: 1.44, 7.51) were found to be independent predictors of adherence.[11] In a study by Holzemer et al., HIV-positive clients with higher symptom scores, particularly depression, were more likely to be nonadherent to medication.[18] Travel distance and economic factors were the main challenges associated with ART adherence in the study by Chindedza et al.[19]

Low adherence rates and suboptimal adherence rates observed may be due to time taken by the patients to get adjusted with treatment schedule, initial side effects, comorbidities, and delay in verification of compliance to ART by health-care workers, etc., Adherence rate was better in stavudine-based regimen than zidovudine-based regimen. Reasons were comparable to the other studies by Amberbir et al., China CARES study, VIDUS, Sasaki et al.[11151620]

Limitations of the study

Adherence was measured through self-reports, routine and random pill counts, and assessment of medical records. These methods are not full proof, and actual adherence could be lesser than what was found. However, due to feasibility issues, it was only possible to use a combination of these methods to minimize error.

Conclusion

Adherence rate was poor among PLWHA, and hence factors affecting adherence has to be addressed to ensure optimal adherence for ART. Economic factors affected adherence, than other factors in this study. Hence, decentralizing the ART center facilities to PHC level and use of alternative strategies such as ART drugs supply similar to the DOTS strategy used in RNTCP is needed. Strengthening IEC activities particularly in the rural areas, with a focus on eliminating the stigma and discrimination, travel concessions in railways and buses for seeking medical care to HIV/AIDS cases is the need of the hour. Provision of social assistance in terms of employment support, monetary or food grains, and moral support is required. Strengthen positive network of people living with HIV/AIDS (PLWHA). Regular ART adherence education and counseling, improved training on medication self-management skills, reminders, improved adherence monitoring, and health-care services should be priority strategies for improving adherence to ART among HIV/AIDS patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.