https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research.

Background 
Human immunodeficiency virus/Acquired immunodeficiency syndrome associated morbidity and mortality has reduced significantly since the introduction of highly active antiretroviral therapy. As a result of increasing access to highly active antiretroviral therapy, the survival and quality of life of the patients has significantly improved globally. Despite this promising result, regular monitoring of people on antiretroviral therapy is recommended to ensure whether there is an effective treatment response or not. This study was designed to assess virological and immunological failure of highly active antiretroviral therapy users among adults and adolescents in the Tigray region of Northern Ethiopia, where scanty data are available.


Methods 
A retrospective follow up study was conducted from September 1 to December 30, 2016 to assess the magnitude and factors associated with virological and immunological failure among 260 adults and adolescents highly active antiretroviral therapy users who started first line ART between January 1, 2008 to March 1, 2016. A standardized questionnaire was used to collect socio-demographic and clinical data. SPSS Version21 statistical software was used for analysis. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated to virological and immunological failure. Statistical association was declared significant if p-value was ≤ 0.05.


Result 
A total of 30 (11.5%) and 17 (6.5%) participants experienced virological and immunological failure respectively in a median time of 36 months of highly active antiretroviral therapy. Virological failure was associated with non-adherence to medications, aged < 40 years old, having CD4+ T-cells count < 250 cells/μL and male gender. Similarly, immunological failure was associated with non-adherence, tuberculosis co-infection and Human immunodeficiency virus RNA ≥1000 copies/mL.


Conclusions 
The current result shows that immunological and virological failure is a problem in a setting where highly active antiretroviral therapy has been largely scale up. The problem is more in patients with poor adherence. This will in turn affect the global targets of 90% viral suppression by 2020. This may indicate the need for more investment and commitment to improving patient adherence in the study area.

/pdf/virological-and-immunological-failure-of-haart-and-2zpen5kyml.pdf

Virological and immunological failure of HAART and associated risk factors among adults and adolescents in the Tigray region of Northern Ethiopia.

Free antiretroviral therapy has been implemented in China since 2004, but adherence to antiretroviral therapy among people living with HIV is suboptimal. The effectiveness of antiretroviral therapy is subject to medication adherence, which decreases with prolonged treatment times. The aim of this study was to investigate medication adherence and related factors among people living with HIV with newly initiated antiretroviral therapy. This observational study was conducted in consecutive samples of people living with HIV who had newly initiated antiretroviral therapy. Participants were recruited between March 1, 2013, and August 31, 2014, from the local Center for Disease Control and Prevention and Infectious Disease hospital in a capital city in central China. A standard set of questionnaires was adopted, including the Community Programs for Clinical Research on AIDS Antiretroviral Medications and Self-Report Questionnaire (CPCRA), the Patient Health Questionnaire-9 (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7). T-test, Chi square test and multivariate logistic regression analysis with backward stepwise were performed to explore factors that might influence medication adherence. Of the 207 participants, 85.5% of the participants (177/207) were categorized with good adherence, and 14.5% (30/207) with poor adherence. The multivariate logistic regression analyses showed that participants with positive depression (OR = 5.95, 95% CI: 2.34–15.11) and without disclosure of their HIV status to others (OR = 2.62, 95% CI: 1.06–6.50) were more susceptible to poor adherence. One-sixth of the participants reported suboptimal medication adherence within the first 6 months. Factors associated with poor adherence included non-disclosure of their HIV status, had positive depression. Tailored interventions, such as effective psychological coping strategies, should be implemented for people living with HIV with newly initiated antiretroviral therapy to improve their medication adherence.

/pdf/medication-adherence-to-antiretroviral-therapy-among-newly-1bqwumicmd.pdf

Medication adherence to antiretroviral therapy among newly treated people living with HIV.

Author(s): Holmes, Charles B; Sikazwe, Izukanji; Sikombe, Kombatende; Eshun-Wilson, Ingrid; Czaicki, Nancy; Beres, Laura K; Mukamba, Njekwa; Simbeza, Sandra; Bolton Moore, Carolyn; Hantuba, Cardinal; Mwaba, Peter; Phiri, Caroline; Padian, Nancy; Glidden, David V; Geng, Elvin | Abstract: BackgroundSurvival represents the single most important indicator of successful HIV treatment. Routine monitoring fails to capture most deaths. As a result, both regional assessments of the impact of HIV services and identification of hotspots for improvement efforts are limited. We sought to assess true mortality on treatment, characterize the extent under-reporting of mortality in routine health information systems in Zambia, and identify drivers of mortality across sites and over time using a multistage, regionally representative sampling approach.Methods and findingsWe enumerated all HIV infected adults on antiretroviral therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia during the 24-month period from 1 August 2013 to 31 July 2015. We identified a probability sample of patients who were lost to follow-up through selecting facilities probability proportional to size and then a simple random sample of lost patients. Outcomes among patients lost to follow-up were incorporated into survival analysis and multivariate regression through probability weights. Of 165,464 individuals (64% female, median age 39 years (IQR 33-46), median CD4 201 cells/mm3 (IQR 111-312), the 2-year cumulative incidence of mortality increased from 1.9% (95% CI 1.7%-2.0%) to a corrected rate of 7.0% (95% CI 5.7%-8.4%) (all ART users) and from 2.1% (95% CI 1.8%-2.4%) to 8.3% (95% CI 6.1%-10.7%) (new ART users). Revised provincial mortality rates ranged from 3-9 times higher than naive rates for new ART users and were lowest in Lusaka Province (4.6 per 100 person-years) and highest in Western Province (8.7 per 100 person-years) after correction. Corrected mortality rates varied markedly by clinic, with an IQR of 3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person-years among new ART users, even after adjustment for clinical (e.g., pretherapy CD4) and contextual (e.g., province and clinic size) factors. Mortality rates (all ART users) were highest year 1 after treatment at 4.6/100 person-years (95% CI 3.9-5.5), 2.9/100 person-years (95% CI 2.1-3.9) in year 2, and approximately 1.6% per year through 8 years on treatment. In multivariate analysis, patient-level factors including male sex and pretherapy CD4 levels and WHO stage were associated with higher mortality among new ART users, while male sex and HIV disclosure were associated with mortality among all ART users. In both cases, being late (g14 days late for appointment) or lost (g90 days late for an appointment) was associated with deaths. We were unable to ascertain the vital status of about one-quarter of those lost and selected for tracing and did not adjudicate causes of death.ConclusionsHIV treatment in Zambia is not optimally effective. The high and sustained mortality rates and marked under-reporting of mortality at the provincial-level and unexplained heterogeneity between regions and sites suggest opportunities for the use of corrected mortality rates for quality improvement. A regionally representative sampling-based approach can bring gaps and opportunities for programs into clear epidemiological focus for local and global decision makers.

/pdf/estimated-mortality-on-hiv-treatment-among-active-patients-3doxv7usxf.pdf

Estimated mortality on HIV treatment among active patients and patients lost to follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based survey.

Objective The rapid scale up of antiretroviral treatment (ART) in sub-Saharan Africa (SSA) has resulted in an increased focus on patient adherence. Non-adherence can lead to drug-resistant HIV caused by failure to achieve maximal viral suppression. Optimal treatment requires the identification of patients at high risk of suboptimal adherence and targeted interventions. The aim of this review was to identify and summarise determinants of adherence to ART among HIV-positive adults. Design Systematic review of adherence to ART in SSA from January 2002 to October 2014. Methods A systematic search was performed in 6 databases (PubMed, Cochrane Library, EMBASE, Web of Science, Popline, Global Health Library) for qualitative and quantitative articles. Risk of bias was assessed. A meta-analysis was conducted for pooled estimates of effect size on adherence determinants. Results Of the 4052 articles screened, 146 were included for final analysis, reporting on determinants of 161 922 HIV patients with an average adherence score of 72.9%. Main determinants of non-adherence were use of alcohol, male gender, use of traditional/herbal medicine, dissatisfaction with healthcare facility and healthcare workers, depression, discrimination and stigmatisation, and poor social support. Promoters of adherence included counselling and education interventions, memory aids, and active disclosure among people living with HIV. Determinants of health status had conflicting influence on adherence. Conclusions The sociodemographic, psychosocial, health status, treatment-related and intervention-related determinants are interlinked and contribute to optimal adherence. Clinics providing ART in SSA should therefore design targeted interventions addressing these determinants to optimise health outcomes.

https://gh.bmj.com/content/bmjgh/1/4/e000125.full.pdf

Susan C Aitken

Papers

Determinants of adherence to antiretroviral therapy among HIV-positive adults in sub-Saharan Africa: a systematic review