Evaluation of non-adherence to anti-retroviral therapy, the associated factors and infant outcomes among HIV-positive pregnant women: a prospective cohort study in Lesotho

Introduction Success in addressing prevention of mother-to-child transmission of HIV depends largely on good adherence to anti-retroviral therapy (ART) by pregnant women. Knowledge of the levels of ART adherence among pregnant women is essential to inform strategies to prevent or reduce HIV transmission rates, particularly in African settings. Aim: the primary objective of this study was to measure adherence to anti-retroviral therapy (ART) among pregnant women living with human immunodeficiency virus (HIV). The secondary objectives were to determine: i) the rate of new infections among children at Mabote Filter Clinic in Maseru, Lesotho whose mothers were enrolled in PMTCT, and ii) the factors associated with non-adherence to ART among pregnant women. Methods In this prospective cohort study, HIV-positive pregnant women receiving antiretroviral therapy (ART) for prevention of mother to child transmission (PMTCT) were followed up to delivery and their children were tested for HIV. We collected socio-demographic information, knowledge of PMTCT and adherence to ART (three-day recall and pill count) including reasons for non-adherence. We also used logistic regression to explore factors associated with non-adherence. Results One hundred and seven women were included. The mean (standard deviation) age of the participants was 28.2 (5.7) years. Most, 81.3% (87/107), were married, only 9.3% (10/107) had a postsecondary education. Two-thirds (63.6%: 68/107) of the participants started ART because of PMTCT. Only 78.5% (84/107) of the participants had adequate knowledge of the importance of PMTCT. The three-day self-reported non-adherence rate at the first visit was 7.5% (95% confidence interval (CI): 3.7, 13.1), but up to 43.4% (95% CI: 35.2, 51.9) using pill count. The most frequently reported reasons for not adhering were: running out of pills (7.5%), nausea (5.6%) and to avoid side-effects (3.7%). Women who were employed (odds ratio (OR) 4.35; 95% CI: 1.38,14.29; p = 0.012) and at a higher gestational age (OR = 1.43; 95% CI: 1.11, 1.85; p = 0.006) were more likely to be non-adherent. Only 1 of the 77 exposed infants was found to be positive for HIV at 6 weeks after birth. Conclusion We found a higher non-adherence rate for participants with pill count compared to a three-day adherence self-report. However, mother to child HIV transmission was relatively low. Lack of employment and relatively high gestational age were found to be predictive factors of non-adherence.


Introduction
Lesotho has the second highest prevalence of Human Immunodeficiency Virus (HIV) in the world (25% among adults).
Among the people living with HIV in Lesotho, women are the most affected and represent 60% of all HIV positive people in all age groups. The prevalence of HIV among pregnant women is estimated at 25.9% [1]. The Mother to Child Transmission (MTCT) rate in the absence of prevention of mother to child transmission (PMTCT) interventions ranges from 20-45%, but can be reduced to less than 5% with effective adherence to antiretroviral therapy (ART). In Lesotho, 60% of all women aged 15+ are HIV positive receiving ART [1]. About 13,000 children are living with HIV in Lesotho [1]. In 2013, Lesotho adopted The WHO guidelines recommending initiation of combination antiretroviral therapy for all HIV-infected pregnant or breast-feeding women, regardless of their CD4 cell count as soon as pregnancy is discovered (option B+) [2]. PMTCT has contributed to reducing the number of new infections in children, with a drop from 4400 new infections in 2009 to 1300 in 2015 [3]. However, non-adherence to ART may compromise the effectiveness of PMTCT. Given the high incidence of HIV in Lesotho and among children in particular, this study sought to evaluate adherence to antiretroviral therapy (ART) among pregnant women living with HIV in Lesotho. This study also aimed to determine: i) the rate of new infections among children at Mabote Filter Clinic in Maseru, Lesotho whose mothers were enrolled in PMTCT and ii) the factors associated with non-adherence to ART among pregnant women.

Methods
We conducted a prospective cohort study at the Mabote Filter clinic at Maseru in Lesotho. 107 HIV positive pregnant women were followed until their child was postnatally tested for HIV. Pregnant women living with HIV were invited to participate in the study. After consent was obtained, participants were individually brought into a separate room and interviewed for 10-15 minutes by counselors. A categorical variable was constructed reflecting two levels of adherence during a three days period namely "missed" (nonadherent, <95%) and "not missed" (adherent, ≥95%) taking medication doses during the past three days. Pill-count adherence

Results
The mean age (SD) of participants was 28.  Table 2. Seventy-seven HIV exposed infants were born to study participants during the study period of which only 1 (1.3%, 95%CI: 0.3% -0.7%) was found positive for HIV-DNA PCR at the age of 6 weeks. The woman who was involved in the only case of transmission had suboptimal pill count adherence at first visit but optimal pill count adherence at the second visit.

Discussion
We noted a discrepancy between pill counts and self-reports, progressive decreases in non-adherence over time and a successful PMTCT program. Self-reported adherence is relatively easy to measure and easy to interpret. However, it is prone to social desirability bias and recall bias. Even though we chose a shorter period of recall (three days), self-reported adherence rates did not reflect pill counts. Even though pill counts may also have errors, this discrepancy warrants concern and points to the need for simple accurate measures of adherence in a clinical setting. Non-adherence at the first visit was high, despite adequate knowledge of the importance of PMTCT. This is in contrast to another study in Botswana in which the level of knowledge was directly proportional to the level of adherence among PMTCT clients [4]. The increments in adherence may point to the effect of repeated adherence counselling and would be suggestive that multiple sessions may create a sustained effect. Furthermore, the second visit pill count SD was higher than first visit, suggesting that the women participating in the study were adjusting to PMTCT, or those who were not adhering did not attend their second visit to the clinic and/or withdrew from the study. The adherence rates presented in this at work. This may be due to concerns about stigma. It is unclear why non-adherence was higher among women at a higher gestational age but could be the effect of adherence waning over time. The rate of HIV transmission in this study was relatively low compared to national averages. This data suggests that Option B+ confers some amount of protection in the absence of optimal adherence.

Conclusion
Adherence to ART is critical for the success of PMTCT programs.

Competing interests
The authors declare no competing interests.  Tables and figure   Table 1: Baseline characteristics by level of adherence (pill count) at first interview