Predictors of adherence among antiretroviral therapy naive patients on first-line regimen at Themba Lethu Clinic inJohannesburg: results from a prospective cohort study

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the Degree of Master of Science in Epidemiology and Biostatistics. Johannesburg, November 2017.Introduction Viral load is the most reliable indicator of poor adherence to anti-retroviral therapy (ART). However, this assay is difficult to implement in resource-limited settings due to financial and technical constraints. Laboratory markers, combined with the patient’s demographic and clinical details, have been described as better proxies of adherence than the current self-reported adherence measures. However, the real diagnostic value of these biomarkers remains unknown. Therefore, the aim of this study was to assess the usefulness of a composite marker to identify poor adherence to ART defined as a detectable plasma viral load in HIV-positive patients on first-line regimen at Themba Lethu Clinic (TLC) in Johannesburg, South Africa Materials and Methods: This study was retrospective cohort analysis of data collected on HIV-positive ART naïve adults initiating first line antiretroviral regimen at TLC following the 2010 South African antiretroviral treatment guidelines. The data collection was carried out as part of the low-cost monitoring (LCM) study at Themba Lethu Clinic in Johannesburg from February 2012 to 2014. The LCM cohort which aims to look at low cost monitoring of HIV treatment in resource limited settings was initiated in 2009 in Johannesburg, South Africa. The study or treatment outcome was failure to suppress viral load (VL ≥ 400 copies/ml) at 6 and at 12 months. Adherence to antiretroviral treatment was assessed using four (4) self-reported adherence (SRA) measures namely: a self-reporting questionnaire, a Visual Analogue Scale (VAS), a pill identification test (PIT) and the Simplified Medication Adherence Questionnaire (SMAQ). The result of each self-reported measure was classified as either positive or negative given a conventional threshold. In our study three (3) self-reported adherence (SRA) measures were combined into a multi-method approach tool which included self-reports combined with VAS and the pill identification test (PIT). Continuous variables were summarized by median with interquartile range. Categorical variables were summarized by giving their frequencies. To compare continuous variables, we used an unpaired t-test if the variable was normally distributed. When continuous variables were compared from baseline to the previous 6 months, a paired t-test was done. In the case of skewed distribution, we used a non-parametric variant of the t-test such as the Mann-Whitney U-test. To compare categorical variables, we used cross-tables with corresponding chi-square test or Fisher exact test. A Modified Poisson Generalized Linear Model (GLM) with robust variance was used to estimate adjusted relative risks (aRR) of failing to suppress viral load at 6 and at 12 months adjusting for age age, gender, self-reported adherence measures, changes in laboratory markers and missed appointments at 6 and 12 months after ART initiation. As there was missing values in the covariatess and the outcome, we performed a multiple imputation technique under missing at random (MAR) assumption in order to compare the robustness of the estimations between the complete case analysis and the imputation model under MAR after imputing missing values. with the imputed dataset. Additionally, we calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each self-reported adherence measure using viral load as the reference standard. Thus, we derived two diagnostic risk scores from rounding and adding together the adjusted regression coefficients used to estimate adjusted relative risk and following the Spiegelhalter and Knill-Jones approach, at 6 and at 12 months. The Receiver Operating characteristic (ROC) curves were computed to see the overall discriminative value of each continuous risk score. To assess the clinical usefulness of the continuous riskscores we dichotomized them from 2 ≥ vs < 1 to 5 ≥ vs < 5 and calculated the sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) at each cut-off, taking detectable viral load as a gold standard. Results: There were 353 HIV-positive patients initiated on first line ART at TLC for the LCM cohort study. Of these, 80.7% did not suppress viral load after 6 months while 30.1% did not suppress viral load at 12 months. The proportion of patients classified as being highly adherent was 86.7% but this proportion decreased to 60% at 12 months. By 6 months, after adjusting for gender and age, the variables that were significantly associated with detectable viral load included: having missed at least two ARV visits by ≥ 7 days (aRR: 2.35 95% CI: 1.08 -5.11); platelet count < 150 cells/mm3 (aRR: 2.73 95% CI: 1.04 -7.18) and VAS ≤ 95% (aRR: 1.65. 95% CI: 1.01-2.71). At 12 months, the estimates showed a positive relationship only with age group and unemployment. There were no similarities in the results found using complete case analysis and analysis with imputed datasets. However, the largest standard errors were obtained from the complete case analysis. At 6 months, the AUC ROC curve was calculated as 0.63 (95% CI, 0.53 - 0.72) while, for the visual analogue scale, the AUC decreased to 0.55 (95% CI, 0.49 - 0.62); for the Simplified Medication Adherence Questionnaire (SMAQ), the AUC decreased to 0.52 (95%CI, 0.45 - 0.60), while for the multi-method approach, it decreased to 0.53 (95% CI, 0.46 - 0.58). The optimal diagnostic accuracy was obtained with the score 5 (≥5 vs <5 Se: 64% and a Sp: 50.0%) followed by a risk score of 4 (Se of 76.0%, Sp of 34.7%). At 12 months, the AUC of the diagnostic risk score was calculated as 0.44 (95%CI, 0.40 - 0.60) while for the three self-reported adherence methods, it decreased to 0.48 (95% CI, 0.40 - 0.60), 0.51 (95%CI, 0.40 - 0.60) and 0.50 (95%CI, 0.41 - 0.59) respectively for the visual analogue scale, the SMAQ and the multi-method approach method respectively. Conclusion. This study shows that after ART initiation, the 6-month’s adherence can be better diagnosed using laboratory markers combined with patient’s information and traditional self-reported adherence measures at Themba Lethu Clinic. The advantage of this proposed method is that it is based on routine and accessible informations collected during HIV-positive patient visits, thus incurring no additional cost for its implementation. An external validation of this diagnostic risk score is needed for its translation into clinical practice in resource-limited settings.LG201

Factors influencing the use of malaria prevention strategies by women in Senegal: a cross-sectional study

Background: The World Health Organization (WHO) recommends the use of insecticide-treated nets (ITNs) and intermittent preventive treatment in pregnancy (IPTp) as a cost-effective intervention for the prevention of malaria during pregnancy in endemic areas. This study was conducted to investigate: (1) the extent of use of both IPTp and ITNs, and (2) conduct multinomial regression to identify factors affecting the optimal usage of IPTp and ITNs among women with a recent pregnancy in Senegal. Methods: Data was drawn from the 2013–2014 Demographic and Health Survey. A total of 4616 women aged 15–49 years old, who had a recent pregnancy were analyzed. Multinomial logistic regression model was used to assess factors associated with optimal uptake of malaria preventive strategies (both IPTp and ITN use). Results: Amongst women who had a recent pregnancy, less than half of them used ITNs (46.84%) however, 80.35% reported taking IPTp during their last pregnancy. Overall, 37.51% reported using the optimal malaria preventive strategies. Women aged 35–49 years and living in the richer or middle wealth quintile were more likely to use optimal prevention methods. Pregnant women living in Diourbel, Saint-Louis, Thies, Louga, Fatick and Matam were more likely to use both IPTp-SP and ITNs compared to those living in Dakar. Additionally, women who initiated antenatal care in at least at 6 weeks of pregnancy or who attended four antenatal visits or more were more likely to use optimal malaria preventive methods during pregnancy. Conclusions: This study has shown important factors that influence the uptake of malaria prevention methods during pregnancy in Senegal. These findings highlight the need for targeted preventive strategies when designing and implementing policies aimed at improving the uptake of these measures during pregnancy in Senegal

Determinants of complete immunization among senegalese children aged 12–23 months: evidence from the demographic and health survey

Abstract Background The expanded Programme on Immunization (EPI) is one of the most cost-effective interventions to reduce childhood mortality and morbidity. However, determinants of childhood immunization have not been well studied in Senegal. Thus, the aim of our study is to assess routine immunization uptake and factors associated with full immunization status among Senegalese children aged 12–23 months. Methods We used the 2010–2011 Senegalese Demographic and Health Survey data. The DHS was a two stages cross-sectional survey carried out in 2010–2011. The analysis included 2199 children aged 12–23 months. The interviewers collected information on vaccine uptake based on information from vaccination cards or maternal recall Univariate and multivariable logistic regressions models were used to identify the determinants of full childhood immunization. Results The prevalence of complete immunization coverage among boys and girls based on both vaccination card information and mothers’ recall was 62.8%. The immunization coverage as documented on vaccination cards was 37.5%. Specific coverage for the single dose of BCG at birth, the third dose of polio vaccine, the third dose of pentavalent vaccine and the first dose of measles vaccine were 94.7%, 72.7%, 82.6%, and 82.1%, respectively. We found that mothers who could show a vaccination card [AOR 7.27 95% CI (5.50–9.60)], attended at least secondary education level [AOR 1.8 95% CI (1.20–2.48)], attended four antenatal visits [AOR 3.10 95% CI (1.69–5.63)], or delivered at a health facility [AOR 1.27 95% CI (1–1.74)] were the predictors of full childhood immunization. Additionally, children living in the eastern administrative regions of the country were less likely to be fully vaccinated [AOR 0.62 95% CI (0.39–0.97)]. Conclusions We found that the full immunization coverage among children aged between 12 and 23 months was below the national (> 80%) and international targets (90%). Geographic area, mother’s characteristics, antenatal care and access to health care services were associated with full immunization. These findings highlight the need for innovative strategies based on a holistic approach to overcome the barriers to childhood immunization in Senegal