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      Self-Reported Side Effects and Adherence to Antiretroviral Therapy in HIV-Infected Pregnant Women under Option B+: A Prospective Study

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          Abstract

          Background

          Antiretroviral therapy (ART) regimens containing efavirenz (EFV) are recommended as part of universal ART for pregnant and breastfeeding women. EFV may have appreciable side effects (SE), and ART adherence in pregnancy is a major concern, but little is known about ART SE and associations with adherence in pregnancy.

          Methods

          We investigated the distribution of patient-reported SE (based on Division of AIDS categories) and the association of SE with missed ART doses in a cohort of 517 women starting EFV+3TC/FTC+TDF during pregnancy. In analysis, SE were considered in terms of their overall frequency, by systems category, and by latent classes.

          Results

          Overall 97% of women reported experiencing at least one SE after ART initiation, with 48% experiencing more than five SE. Gastrointestinal, central nervous system, systemic and skin SE were reported by 81%, 85%, 79% and 31% of women, respectively, with considerable overlap across groups. At least one missed dose was reported by 32% of women. In multivariable models, ART non-adherence was associated with systemic SE compared to other systems categories, and measures of the overall burden of SE experienced were most strongly associated with missed ART doses.

          Conclusion

          These data demonstrate very high levels of SE in pregnant women initiating EFV-based ART and a strong association between SE burden and ART adherence. ART regimens with reduced SE profiles may enhance adherence, and as countries expand universal ART for all adult patients, counseling must include preparation for ART SE.

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          Most cited references28

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          Barriers and facilitating factors to the uptake of antiretroviral drugs for prevention of mother-to-child transmission of HIV in sub-Saharan Africa: a systematic review

          Objectives To investigate and synthesize reasons for low access, initiation and adherence to antiretroviral drugs by mothers and exposed babies for prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa. Methods A systematic literature review was conducted. Four databases were searched (Medline, Embase, Global Health and Web of Science) for studies conducted in sub-Saharan Africa from January 2000 to September 2012. Quantitative and qualitative studies were included that met pre-defined criteria. Antiretroviral (ARV) prophylaxis (maternal/infant) and combination antiretroviral therapy (ART) usage/registration at HIV care and treatment during pregnancy were included as outcomes. Results Of 574 references identified, 40 met the inclusion criteria. Four references were added after searching reference lists of included articles. Twenty studies were quantitative, 16 were qualitative and eight were mixed methods. Forty-one studies were conducted in Southern and East Africa, two in West Africa, none in Central Africa and one was multi-regional. The majority (n=25) were conducted before combination ART for PMTCT was emphasized in 2006. At the individual-level, poor knowledge of HIV/ART/vertical transmission, lower maternal educational level and psychological issues following HIV diagnosis were the key barriers identified. Stigma and fear of status disclosure to partners, family or community members (community-level factors) were the most frequently cited barriers overall and across time. The extent of partner/community support was another major factor impeding or facilitating the uptake of PMTCT ARVs, while cultural traditions including preferences for traditional healers and birth attendants were also common. Key health-systems issues included poor staff-client interactions, staff shortages, service accessibility and non-facility deliveries. Conclusions Long-standing health-systems issues (such as staffing and service accessibility) and community-level factors (particularly stigma, fear of disclosure and lack of partner support) have not changed over time and continue to plague PMTCT programmes more than 10 years after their introduction. The potential of PMTCT programmes to virtually eliminate vertical transmission of HIV will remain elusive unless these barriers are tackled. The prominence of community-level factors in this review points to the importance of community-driven approaches to improve uptake of PMTCT interventions, although packages of solutions addressing barriers at different levels will be important.
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            A Systematic Review of Individual and Contextual Factors Affecting ART Initiation, Adherence, and Retention for HIV-Infected Pregnant and Postpartum Women

            Background Despite progress reducing maternal mortality, HIV-related maternal deaths remain high, accounting, for example, for up to 24 percent of all pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART) is effective in improving outcomes among HIV-infected pregnant and postpartum women, yet rates of initiation, adherence, and retention remain low. This systematic literature review synthesized evidence about individual and contextual factors affecting ART use among HIV-infected pregnant and postpartum women. Methods Searches were conducted for studies addressing the population (HIV-infected pregnant and postpartum women), intervention (ART), and outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. Individual and contextual enablers and barriers to ART use were extracted and organized thematically within a framework of individual, interpersonal, community, and structural categories. Results Thirty-four studies were included in the review. Individual-level factors included both those within and outside a woman’s awareness and control (e.g., commitment to child’s health or age). Individual-level barriers included poor understanding of HIV, ART, and prevention of mother-to-child transmission, and difficulty managing practical demands of ART. At an interpersonal level, disclosure to a spouse and spousal involvement in treatment were associated with improved initiation, adherence, and retention. Fear of negative consequences was a barrier to disclosure. At a community level, stigma was a major barrier. Key structural barriers and enablers were related to health system use and engagement, including access to services and health worker attitudes. Conclusions To be successful, programs seeking to expand access to and continued use of ART by integrating maternal health and HIV services must identify and address the relevant barriers and enablers in their own context that are described in this review. Further research on this population, including those who drop out of or never access health services, is needed to inform effective implementation.
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              The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: A systematic review and meta-analysis

              Poor adherence to antiretroviral therapies (ARTs) in human immunodeficiency virus (HIV)-infected patients increases the risk of incomplete viral suppression, development of viral resistance, progression to acquired immune deficiency syndrome and death. This study assesses the impact of specific treatment-related adverse events (AEs) on adherence to ART in the adult HIV patient population. A systematic review of studies involving adult HIV-infected patients aged ≥ 16 years that reported an odds ratio (OR) for factors affecting adherence to ART was conducted through a search of the EMBASE® and Medline® databases. Database searches were complemented with a search of titles in the bibliographies of review papers. Studies conducted in populations limited to a particular demographic characteristic or behavioural risk were excluded. To qualify for inclusion into a meta-analysis, treatment-related AEs had to be defined similarly across studies. Also, multiple ORs from the same study were included where study sub-groups were distinct. Random effects models were used to pool ORs. In total, 19 studies and 18 ART-related AEs were included in meta-analyses. Adherence to ART was significantly lower in patients with non-specific AEs than in patients who did not experience AEs [OR = 0.623; 95% confidence interval (CI): 0.465–0.834]. Patients with specific AEs such as fatigue (OR = 0.631; 95% CI: 0.433–0.918), confusion (OR = 0.349; 95% CI: 0.184–0.661), taste disturbances (OR = 0.485; 95% CI: 0.303–0.775) and nausea (OR = 0.574; 95% CI: 0.427–0.772) were significantly less likely to adhere to ART compared to patients without these AEs. Knowledge of specific treatment-related AEs may allow for targeted management of these events and a careful consideration of well-tolerated treatment regimens to improve ART adherence and clinical outcomes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 October 2016
                2016
                : 11
                : 10
                : e0163079
                Affiliations
                [1 ]Division of Epidemiology & Biostatistics, University of Cape Town, Cape Town, South Africa
                [2 ]Centre for Infectious Diseases Epidemiology & Research, University of Cape Town, Cape Town, South Africa
                [3 ]HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, Columbia University, New York, NY, United States of America
                [4 ]Anova Health Institute, Johannesburg, South Africa
                [5 ]Department of Obstetrics & Gynaecology, University of Cape Town, Cape Town, South Africa
                [6 ]New Somerset Hospital, Cape Town, South Africa
                [7 ]ICAP, Columbia University, Mailman School of Public Health, New York, NY, United States of America
                [8 ]College of Physicians & Surgeons, Columbia University, New York, NY, United States of America
                University of Maryland School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: TP LM EJA AC JAM.

                • Formal analysis: TP AC LM.

                • Methodology: AC.

                • Resources: CAM RHR.

                • Supervision: LM EJA.

                • Visualization: TP AC LM.

                • Writing – original draft: TP AC.

                • Writing – review & editing: LM EJA RHR CAM JAM GP.

                Author information
                http://orcid.org/0000-0003-4554-2922
                Article
                PONE-D-16-13067
                10.1371/journal.pone.0163079
                5070813
                27760126
                42029a3b-ba94-4963-a00a-a16af3f07f00
                © 2016 Phillips et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 March 2016
                : 2 September 2016
                Page count
                Figures: 3, Tables: 2, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000071, National Institute of Child Health and Human Development;
                Award ID: 1R01HD074558
                Award Recipient :
                Funded by: HIV Center for Clinical and Behavioral Studies
                Award ID: P30-MH43520
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004513, Harry Crossley Foundation;
                Award ID: Harry Crossley Senior Clinical Fellowship 2015-2016
                Award Recipient :
                This research was funded by the President's Emergency Plan for AIDS Relief (PEPFAR) through the National Institute of Child Health and Human Development (NICHD), grant number 1R01HD074558( https://www.nichd.nih.gov/grants-funding/Pages/default.aspx). Drs. Mellins and Remien were also supported by the HIV Center for Clinical and Behavioral Studies (P30-MH43520 ( http://www.cumc.columbia.edu/publications/press_releases/hiv_center.html) and Annibale Cois was supported by the Harry Crossley Foundation (Harry Crossley Senior Clinical Fellowship 2015-2016). Tamsin Phillips is supported by a bursary from the South African Centre for Epidemiological Modelling and Analysis. Additional funding comes from the Elizabeth Glaser Pediatric AIDS Foundation ( http://www.pedaids.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                The variables and observations included in this report are provided as supporting information. However, because data collection for the parent study ( https://clinicaltrials.gov/ct2/show/NCT01933477) is ongoing, the full study dataset will not be available until mid-2017 approximately. At that time, the data will be housed in a standard data repository linked to the Centre for Infectious Diseases Epidemiology & Research at the University of Cape Town, South Africa. The Supporting Information file contains the minimal data set underlying the findings of this specific study.

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