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Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia

BACKGROUND: Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out...

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Autores principales: Mody, Aaloke, Sikazwe, Izukanji, Czaicki, Nancy L., Wa Mwanza, Mwanza, Savory, Theodora, Sikombe, Kombatende, Beres, Laura K., Somwe, Paul, Roy, Monika, Pry, Jake M., Padian, Nancy, Bolton-Moore, Carolyn, Holmes, Charles B., Geng, Elvin H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988277/
https://www.ncbi.nlm.nih.gov/pubmed/29870531
http://dx.doi.org/10.1371/journal.pmed.1002574
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author Mody, Aaloke
Sikazwe, Izukanji
Czaicki, Nancy L.
Wa Mwanza, Mwanza
Savory, Theodora
Sikombe, Kombatende
Beres, Laura K.
Somwe, Paul
Roy, Monika
Pry, Jake M.
Padian, Nancy
Bolton-Moore, Carolyn
Holmes, Charles B.
Geng, Elvin H.
author_facet Mody, Aaloke
Sikazwe, Izukanji
Czaicki, Nancy L.
Wa Mwanza, Mwanza
Savory, Theodora
Sikombe, Kombatende
Beres, Laura K.
Somwe, Paul
Roy, Monika
Pry, Jake M.
Padian, Nancy
Bolton-Moore, Carolyn
Holmes, Charles B.
Geng, Elvin H.
author_sort Mody, Aaloke
collection PubMed
description BACKGROUND: Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia’s HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. METHODS AND FINDINGS: We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28–41], median CD4 268 cells/μL [IQR 134–430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%–16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%–6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%–13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%–49.9%), 13.6% increase in retention at six months (95% CI, 7.3%–20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%–41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%–46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. CONCLUSIONS: In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards.
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spelling pubmed-59882772018-06-16 Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia Mody, Aaloke Sikazwe, Izukanji Czaicki, Nancy L. Wa Mwanza, Mwanza Savory, Theodora Sikombe, Kombatende Beres, Laura K. Somwe, Paul Roy, Monika Pry, Jake M. Padian, Nancy Bolton-Moore, Carolyn Holmes, Charles B. Geng, Elvin H. PLoS Med Research Article BACKGROUND: Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia’s HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. METHODS AND FINDINGS: We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28–41], median CD4 268 cells/μL [IQR 134–430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%–16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%–6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%–13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%–49.9%), 13.6% increase in retention at six months (95% CI, 7.3%–20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%–41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%–46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. CONCLUSIONS: In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards. Public Library of Science 2018-06-05 /pmc/articles/PMC5988277/ /pubmed/29870531 http://dx.doi.org/10.1371/journal.pmed.1002574 Text en © 2018 Mody et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mody, Aaloke
Sikazwe, Izukanji
Czaicki, Nancy L.
Wa Mwanza, Mwanza
Savory, Theodora
Sikombe, Kombatende
Beres, Laura K.
Somwe, Paul
Roy, Monika
Pry, Jake M.
Padian, Nancy
Bolton-Moore, Carolyn
Holmes, Charles B.
Geng, Elvin H.
Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia
title Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia
title_full Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia
title_fullStr Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia
title_full_unstemmed Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia
title_short Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia
title_sort estimating the real-world effects of expanding antiretroviral treatment eligibility: evidence from a regression discontinuity analysis in zambia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988277/
https://www.ncbi.nlm.nih.gov/pubmed/29870531
http://dx.doi.org/10.1371/journal.pmed.1002574
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