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      Adherence to Antiretroviral Therapy During and After Pregnancy: Cohort Study on Women Receiving Care in Malawi's Option B+ Program

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          Abstract

          One-third of women enrolled in Malawi's program to prevent human immunodeficiency virus mother-to-child-transmission (Option B+) adhered inadequately to antiretroviral therapy during pregnancy and breastfeeding. Long-term virological outcomes must be closely monitored, and effective interventions to improve adherence should be deployed.

          Abstract

          Background.  Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART.

          Methods.  We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days “covered” by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease.

          Results.  Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4–21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center.

          Conclusions.  One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented.

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          Most cited references21

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          Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance.

          Nonadherence to highly active antiretroviral therapy (HAART) is a major cause of human immunodeficiency virus (HIV) drug resistance; however the level of nonadherence associated with the greatest risk of resistance is unknown. Beginning in February 2000, 195 patients at the Johns Hopkins Outpatient Center (Baltimore, MD) who were receiving HAART and who had HIV loads of <500 copies/mL were recruited into a cohort study and observed for 1 year. At each visit, adherence to HAART was assessed and plasma samples were obtained and stored for resistance testing, if indicated. The overall incidence of viral rebound with clinically significant resistance was 14.5 cases per 100 person-years. By multivariate Cox proportional hazards regression, a cumulative adherence of 70%-89%, a CD4 cell nadir of <200 cells/microL, and the missing of a scheduled clinic visit in the past month were independently associated with an increased hazard of viral rebound with clinically significant resistance. Clinicians and patients must set high adherence goals to avoid the development of resistance.
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            Adherence to nonnucleoside reverse transcriptase inhibitor-based HIV therapy and virologic outcomes.

            Adherence of 95% or more to unboosted protease regimens is required for optimal virologic suppression in HIV-1-infected patients. Whether the same is true for nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy is unclear. To assess the relationship between adherence to NNRTI-based therapy and viral load in treatment-naive patients. Observational cohort study. Private-sector HIV and AIDS disease management program in South Africa. 2821 adults infected with HIV who began NNRTI-based therapy between January 1998 and March 2003 (2764 patients [98%] were enrolled after December 2000). Adherence was assessed by monthly pharmacy claims. The primary end point was sustained viral load suppression ( 400 copies/mL). The median follow-up period was 2.2 years (interquartile range, 1.7 to 2.7 years). The proportion of patients with sustained viral load suppression ranged from 13% (41 of 325 patients) in patients who filled less than 50% of antiretroviral drug prescriptions to 73% (725 of 997 patients) in those who filled 100% of antiretroviral drug prescriptions. Each 10% increase in pharmacy claim adherence greater than 50% was associated with a mean absolute increase of 0.10 in the proportion of patients with sustained virologic suppression (P 0.20 x 10(9) cells/L), baseline viral load greater than 10(5) copies/mL (hazard ratio, 1.39 [CI, 1.14 to 1.70]), nevirapine-based regimen (hazard ratio, 1.43 [CI, 1.16 to 1.75]), and low pharmacy claim adherence (hazard ratio, 1.58 [CI, 1.48 to 1.69], per 10% decrease in adherence to 50%). Observational study with adherence stratification at study end and lack of standardized timing for outcome measurement. Virologic outcomes improve in a linear dose-response manner as adherence to NNRTI-based regimens increases beyond 50%.
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              Adherence to highly active antiretroviral therapy assessed by pharmacy claims predicts survival in HIV-infected South African adults.

              It is unclear how adherence to highly active antiretroviral therapy (HAART) may best be monitored in large HIV programs in sub-Saharan Africa where it is being scaled up. We aimed to evaluate the association between HAART adherence, as estimated by pharmacy claims, and survival in HIV-1-infected South African adults enrolled in a private-sector AIDS management program. Of the 6288 patients who began HAART between January 1999 and August 2004, 3805 (61%) were female and 6094 (97%) were black African. HAART adherence was >or=80% for 3298 patients (52%) and 100% for 1916 patients (30%). Women were significantly more likely to have adherence>or=80% than men (54% vs 49%, P 200 cells/microL). Pharmacy-based records may be a simple and effective population-level tool for monitoring adherence as HAART programs in Africa are scaled up.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                01 November 2016
                26 July 2016
                26 July 2016
                : 63
                : 9
                : 1227-1235
                Affiliations
                [1 ]Institute of Social & Preventive Medicine
                [2 ]Department of Infectious Diseases, Bern University Hospital, University of Bern, Switzerland
                [3 ]Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa
                [4 ]The Baobab Health Trust
                [5 ]International Training & Education Center for Health
                [6 ]Lighthouse Trust
                [7 ]Department of HIV and AIDS, Ministry of Health, Lilongwe
                [8 ]Dignitas International, Zomba
                [9 ]Department of Medicine, College of Medicine, University of Malawi, Blantyre
                [10 ]The International Union Against Tuberculosis and Lung Disease, Paris, France
                Author notes
                Correspondence: A. D. Haas, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland ( andreas.haas@ 123456ispm.unibe.ch ).
                Article
                ciw500
                10.1093/cid/ciw500
                5064160
                27461920
                e388b0d8-9a6d-4939-8bb0-9ccd6b901d44
                © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@ 123456oup.com .

                History
                : 3 May 2016
                : 17 July 2016
                Funding
                Funded by: Bill and Melinda Gates Foundation;
                Award ID: OPP1090200
                Funded by: United States Agency for International Development–National Institutes of Health initiative Partnerships for Enhanced Engagement in Research Health;
                Award ID: AID-OAA-A-11-00012
                Funded by: National Institute of Allergy and Infectious Diseases;
                Award ID: 5U01-AI069924
                Funded by: Centers for Disease Control and Prevention;
                Funded by: Swiss National Science Foundation;
                Award ID: 3233B-150934
                Categories
                HIV/AIDS

                Infectious disease & Microbiology
                adherence,antiretroviral therapy,option b+,mother-to-child-transmission,hiv

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