Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: A systematic review and meta-analysis

aDepartment of International Health bDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA cDepartment of Medicine dCentre for Infectious Diseases eCenter for Evidence-based Healthcare, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa fDepartment of Primary Care Sciences, Keele University, Staffordshire, UK gDepartment of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, Maryland, USA hHuman Sciences Research Council, Pretoria iUniversity of the Free State, Bloemfontein jDepartment of Pediatrics and Child Health, Tygerberg's Children Hospital, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa kFaculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada lTrend Research Centre, Asia University, Taichung, Taiwan mCentre for Infectious Disease Research, Lusaka, Zambia nUniversity of Alabama at Birmingham, Birmingham, Alabama, USA oAnova Health Institute, Johannesburg pSchool of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa qPediatric, Adolescent and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
AIDS (London, England) (Impact Factor: 5.55). 08/2012; 26(16):2039-2052. DOI: 10.1097/QAD.0b013e328359590f
Source: PubMed


OBJECTIVE:: To estimate antiretroviral therapy (ART) adherence rates during pregnancy and postpartum in high-income, middle-income, and low-income countries. DESIGN:: Systematic review and meta-analysis. METHODS:: MEDLINE, EMBASE, SCI Web of Science, NLM Gateway, and Google scholar databases were searched. We included all studies reporting adherence rates as a primary or secondary outcome among HIV-infected pregnant women. Two independent reviewers extracted data on adherence and study characteristics. A random-effects model was used to pool adherence rates; sensitivity, heterogeneity, and publication bias were assessed. RESULTS:: Of 72 eligible articles, 51 studies involving 20 153 HIV-infected pregnant women were included. Most studies were from United States (n = 14, 27%) followed by Kenya (n = 6, 12%), South Africa (n = 5, 10%), and Zambia (n = 5, 10%). The threshold defining good adherence to ART varied across studies (>80, >90, >95, 100%). A pooled analysis of all studies indicated a pooled estimate of 73.5% [95% confidence interval (CI) 69.3-77.5%] of pregnant women who had adequate (>80%) ART adherence. The pooled proportion of women with adequate adherence levels was higher during the antepartum (75.7%, 95% CI 71.5-79.7%) than during postpartum (53.0%, 95% CI 32.8-72.7%; P = 0.005). Selected reported barriers for nonadherence included physical, economic and emotional stresses, depression (especially postdelivery), alcohol or drug use, and ART dosing frequency or pill burden. CONCLUSION:: Our findings indicate that only 73.5% of pregnant women achieved optimal ART adherence. Reaching adequate ART adherence levels was a challenge in pregnancy, but especially during the postpartum period. Further research to investigate specific barriers and interventions to address them is urgently needed globally.

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Available from: Yuh-Shan Ho, Dec 18, 2013
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    • "Enrolling from PMTCT services was also associated with high attrition. This has been observed in a number of African programs [38, 39], and is a challenge worth addressing as countries begin to implement for life-long ART for all pregnant and breastfeeding women. The finding that men had higher attrition than women is not uncommon in African HIV treatment programs [40–44]; this is a high risk group that requires targeted interventions to minimize attrition. "
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    ABSTRACT: Background We report levels and determinants of attrition in Rwanda, one of the few African countries with universal ART access. Methods We analyzed data abstracted from health facility records of a nationally representative sample of adults [≥18 years] who initiated ART 6, 12, and 18 months prior to data collection; and collected facility characteristics with a health facility assessment questionnaire. Weighted proportions and rates of attrition [loss to follow-up or death] were calculated, and patient- and health facility-level factors associated with attrition examined using Cox proportional hazard models. Results 1678 adults initiated ART 6, 12 and 18 months prior to data collection, with 1508 person-years [PY] on ART. Attrition was 6.8% [95% confidence interval [CI] 6.0-7.8]: 2.9% [2.4-3.5] recorded deaths and 3.9% [3.4-4.5] lost to follow-up. Population attrition rate was 7.5/100PY [6.1-9.3]. Adjusted hazard ratio [aHR] for attrition was 4.2 [3.0-5.7] among adults enrolled from in-patient wards [vs 2.2 [1.6-3.0] from PMTCT, ref: VCT]. Compared to adults who initiated ART 18 months earlier, aHR for adults who initiated ART 12 and 6 months earlier was 1.8 [1.3-2.5] and 1.3 [0.9-1.9] respectively. Male aHR was 1.4 [1.0-1.8]. AHR of adults enrolled at urban health facilities was 1.4 [1.1-1.8, ref: rural health facilities]. AHR for adults with CD4+ ≥200 cells/μL vs <200 cells/μL was 0.8 [0.6-1.0]; and adults attending facilities with performance-based financing since 2004–2006 [vs. 2007–2008] had aHR 0.8 [0.6-0.9]. Conclusions Attrition was low in the Rwandan national program. The above patient and facility correlates of attrition can be the focus of interventions to sustain high retention.
    Full-text · Article · Aug 2014 · BMC Public Health
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    • "factors can reduce adherence [9] [10]. Antiretroviral drugs are also used for HIV prevention in a variety of settings, including prevention of mother-to-child transmission, pre-exposure prophylaxis in HIVuninfected individuals (PrEP), and " treatment for prevention " in HIVinfected individuals [11] [12] [13]. "
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    ABSTRACT: Background: Antiretroviral drugs are used for the treatment and prevention of HIV infection. Non-adherence to antiretroviral drug regimens can compromise their clinical efficacy and lead to emergence of drug-resistant HIV. Clinical trials evaluating antiretroviral regimens for HIV treatment and prevention can also be compromised by poor adherence and non-disclosed off-study antiretroviral drug use. This report describes the development and validation of a high throughput, qualitative method for the identification of antiretroviral drugs using high-resolution mass spectrometry (HRMS) for the retrospective assessment of off-study antiretroviral drug use and the determination of potential antiretroviral therapy (ART) non-compliance. Methods: Serum standards were prepared that contained 15 antiretroviral drugs: 9 protease inhibitors (PIs), 4 nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs), and 2 non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs). Analytical separation was achieved on a Hypersil Gold PFP (100×3mm) column and the eluent was analyzed using the Thermo Exactive Orbitrap mass spectrometer (Exactive-MS) operated in full scan mode. Limit of identification, signal intensity precision, retention time analysis, selectivity, and carryover studies were conducted. Concordance with liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods was evaluated using remnant plasma samples from a clinical trial. Results: The limit of identification ranged from 5 to 10ng/ml for 14 drugs (9 PIs, 1 NNRTI, 4 NRTIs) and was 150ng/ml for 1 NNRTI. Precision studies with high and low control mixtures revealed signal intensity coefficients of variation of 3.0-27.5%. The Exactive-MS method was selective for the compounds of interest. Overall, concordance ranged from 89.1% to 100% for the screening of antiretroviral drugs in clinical plasma specimens as compared to LC-MS/MS methods. Conclusion: Using the Exactive-MS, we developed and validated a highly selective, robust method for the multiplexed detection of 15 antiretroviral drugs.
    Full-text · Article · Mar 2014 · Clinica chimica acta; international journal of clinical chemistry
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    • "Evaluation of the impact of prevention of mother-to-child transmission (PMTCT) of HIV programmes, particularly provision of triple antiretroviral drugs (ARVs) to pregnant women, is done at different levels: process (intervention carried out as intended), adherence (intervention worked as intended or compliance) and outcome (intervention decreased the health problem or effectiveness: real life as opposed to research settings) levels. While there are two systematic reviews with meta-analyses that reported on process and intermediary indicators (Nachega et al., 2012; Wettstein et al., 2012), to date no published review has summarized the ultimate effectiveness of triple ARVs given as therapy or prophylaxis, in reducing new HIV infections in children from Sub-Sahara African, using outcome indicators such as mother-to-child transmission (MTCT) rate. Here, we report some methodological challenges identified when conducting a systematic review and meta-analyses on this topic to illustrate the need for better studies to be able to determine the impact of such interventions in programmatic settings. "
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    ABSTRACT: We report on data limitations when conducting systematic review and meta-analysis on the effect of triple antiretroviral drugs on mother-to-child transmission risk of HIV in sub-Saharan Africa. Data published since 2007 lag behind current prevention programme realities and long-term effectiveness studies are limited. There is considerable betweenstudies heterogeneity and the preventive effect is context specific. Competing risk for infection (weaning) is rarely considered in individual studies, leading to incorrect estimation of the postnatal transmission rate. Non-biomedical risk factors of transmission (e.g. adherence, health systems performance) are not usually reported. Studies using primary data and systematic review should consider these challenges.
    Full-text · Article · Jan 2014
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