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      Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis

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          Abstract

          Objective:

          Adolescent and young adult (AYA) populations (12–24 years) represent over 40% of new HIV infections globally. Adolescence is sometimes characterized by high-risk sexual behaviour and a lack of engagement with healthcare services that can affect adherence to antiretroviral therapy (ART). Despite adherence to ART being critical in controlling viral replication, maintaining health and reducing onward viral transmission, there are limited data on ART adherence amongst AYA globally. We undertook a systematic review and meta-analysis of published studies reporting adherence to ART for AYA living with HIV.

          Design and methods:

          Searches included Embase, Medline and PsychINFO databases up to 14 August 2013. Eligible studies defined adequate adherence as at least 85% on self-report or undetectable blood plasma virus levels. A random effects meta-analysis was performed and heterogeneity examined using meta-regression.

          Results:

          We identified 50 eligible articles reporting data from 53 countries and 10 725 patients. Using a pooled analysis of all eligible studies, 62.3% [95% confidence interval (CI) 57.1–67.6; I 2 : 97.2%] of the AYA population were adherent to therapy. The lowest average ART adherence was in North America [53% (95% CI 46–59; I 2 : 91%)], Europe [62% (95% CI 51–73; I 2 : 97%)] and South America [63% (95% CI 47–77; I 2 : 85%] and, with higher levels in Africa [84% (95% CI 79–89; I 2 : 93%)] and Asia [84% (95% CI 77–91; I 2 : 0%].

          Conclusion:

          Review of published literature from Africa and Asia indicate more than 70% of HIV-positive AYA populations receiving ART are adherent to therapy and lower rates of adherence were shown in Europe and North America at 50–60%. The global discrepancy is probably multifactorial reflecting differences between focused and generalised epidemics, access to healthcare and funding.

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          Most cited references36

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          Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa.

          To determine adherence to and effectiveness of antiretroviral therapy (ART) in adolescents vs. adults in southern Africa. Observational cohort study. Aid for AIDS, a private sector disease management program in southern Africa. Adolescents (age 11-19 years; n = 154) and adults (n = 7622) initiating ART between 1999 and 2006 and having a viral load measurement within 1 year after ART initiation. Primary: virologic suppression (HIV viral load < or = 400 copies/mL), viral rebound, and CD4 T-cell count at 6, 12, 18, and 24 months after ART initiation. Secondary: adherence assessed by pharmacy refills at 6, 12, and 24 months. Multivariate analyses: loglinear regression and Cox proportional hazards. A significantly smaller proportion of adolescents achieved 100% adherence at each time point (adolescents: 20.7% at 6 months, 14.3% at 12 months, and 6.6% at 24 months; adults: 40.5%, 27.9%, and 20.6% at each time point, respectively; P < 0.01). Patients achieving 100% 12-month adherence were significantly more likely to exhibit virologic suppression at 12 months, regardless of age. However, adolescents achieving virologic suppression had significantly shorter time to viral rebound (adjusted hazard ratio 2.03; 95% confidence interval: 1.31 to 3.13; P < 0.003). Adolescents were less likely to experience long-term immunologic recovery despite initial CD4 T-cell counts comparable to adults. Compared with adults, adolescents in southern Africa are less adherent to ART and have lower rates of virologic suppression and immunologic recovery and a higher rate of virologic rebound after initial suppression. Studies must determine specific barriers to adherence in this population and develop appropriate interventions.
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            Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression.

            For antiretroviral therapy, the 95% adherence "threshold" is based on nucloside-exposed patients who are receiving partially suppressive, unboosted protease inhibitor regimens. Using unannounced pill counts and electronic medication monitoring, viral suppression is common with a 54%-100% mean adherence level to nonnucleoside reverse-transcriptase-inhibitor regimens. Although perfect adherence is an important goal, viral suppression is possible with moderate adherence to potent regimens.
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              A comparison study of multiple measures of adherence to HIV protease inhibitors.

              Poor adherence to HIV protease inhibitors may compromise the effectiveness of treatment. Few studies have compared methods for measuring adherence or have related adherence measures to a clinical outcome. To examine the relationship among a composite score of adherence, the three primary measures of adherence, and HIV virologic response. Longitudinal cohort study. Public HIV clinic. 108 HIV-infected adults receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitors who were monitored for 666 monthly intervals. Medication Event Monitoring System (MEMS), pill count, and interview combined into a composite adherence score (CAS), and HIV viral load. Mean antiretroviral adherence differed by adherence measure (MEMS, 0.63; pill count, 0.83; interview, 0.93; and CAS, 0.76). Composite adherence score decreased significantly over time. Composite adherence score, MEMS values, pill values, and interview values were statistically significantly associated with achievement of an undetectable viral load within 6 months of initiating therapy. Composite adherence score showed the strongest predictive relationship (odds ratios for a 10% increase in adherence for CAS, MEMS, pill count, and interview, respectively, were 1.26 [95% CI, 1.16 to 1.37], 1.13 [CI, 1.06 to 1.21], 1.10 [CI, 1.02 to 1.19], and 1.35 [CI, 0.94 to 1.94]). Different measures applied to the same patient suggest different levels of adherence. Adherence may be underestimated by MEMS and overestimated by pill count and interview. A summary measure combining several measures is more strongly related to a clinical response, but more practical measurement methods are needed for clinical use.
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                Author and article information

                Journal
                AIDS
                AIDS
                AIDS
                AIDS (London, England)
                Lippincott Williams & Wilkins
                0269-9370
                1473-5571
                24 August 2014
                30 July 2014
                : 28
                : 13
                : 1945-1956
                Affiliations
                [a ]School of Medicine
                [b ]Infectious Disease Epidemiology, School of Public Health
                [c ]Communicable Diseases Section, Department of Medicine, Imperial College London, London, UK.
                Author notes
                Correspondence to Sung-Hee Kim, Department of Medicine, School of Public Health, Norfolk Place, London W2 1PG, UK. Tel: +44 75009700080; e-mail: Sung-hee.kim08@ 123456imperial.ac.uk
                Article
                10.1097/QAD.0000000000000316
                4162330
                24845154
                f9c4c378-6d1c-4231-bf08-64097ea23c5a
                © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

                This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 25 November 2013
                : 26 March 2014
                : 24 April 2014
                Categories
                Epidemiology and Social
                Custom metadata
                TRUE

                adolescence,antiretroviral therapy,highly active,hiv,medication adherence,patient compliance,young adult

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