Adherence to Antiretroviral Therapy During and After Pregnancy in Low-, Middle and High
Income Countries: A Systematic Review and Meta-Analysis
Jean B. Nachega1,2, Olalekan A. Uthman2,3, Jean Anderson2, Karl Peltzer4, Sarah Wampold1, Mark Cotton2, Edward J. Mills5,
Yuh-Shan Ho6, Jeffrey S. A. Stringer7, James McIntyre8, and Lynne Mofenson9
1) Johns Hopkins University, USA; 2) Stellenbosch University, South Africa; 3) Keele University, UK; 4) University of the Free State, South Africa; 5) University of Ottawa, Canada;
;6) Asia University, Taiwan; 7) University of Alabama at Birmingham, USA; 8) University of Cape Town, South Africa; and 9) NICHD/National Institutes of Health, USA.
Context: Data on antiretroviral therapy (ART) adherence during pregnancy are
limited, and no systematic review has been published.
Objective: To estimate ART adherence rates during pregnancy and postpartum in
high-, middle- and low-income countries.
Data source: Search of MEDLINE, EMBASE, SCI Web of Science, NLM Gateway
and Google scholar databases and manual search of retrieved articles’
Study selection: All studies reporting adherence as a primary or secondary outcome
among HIV-infected pregnant women.
Data extraction: 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, 51studies 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%, I2=97.7%) of pregnant women 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 the postpartum
period (53.0%, 95% 32.8% to 72.7%) (p=0.005).
Conclusions: Our findings indicate that only 73.5% of pregnant women achieves
good enough ART adherence. Optimal adherence remains a challenge in pregnancy,
but especially during the postpartum period. Investigation of specific risk factors and
interventions to address them are urgently needed globally.
We first stabilized the raw ART adherence proportions from each
study using the Freeman-Tukey variant of the arcsine square root
transformed proportion suitable for pooling. We used a
DerSimonian-Laird random effects model due to anticipated
variations in study population, health care delivery systems and
Our meta-analysis showed ART adherence during pregnancy and postpartum is
significantly below that recommended for adequate virologic suppression.
Optimal adherence remains a challenge in both high- and low-income countries
during pregnancy and particularly during the postpartum period. It is crucial to
monitor ART adherence, investigate specific risk factors for non-adherence, and
develop interventions to assist ante- and postpartum women in adhering to ART
to ensure the long-term efficacy of ART for both maternal health and PMTCT.
Globally, ~1.4 million HIV-infected women give birth each
year, 91% of whom reside in sub-Saharan Africa.
Antiretroviral therapy (ART) use during and after pregnancy
is critical for preserving maternal health and preventing
mother-to-child HIV transmission (PMTCT). In high-income
countries, MTCT rates as low as 1-2% have been achieved
with combination ART (cART) during pregnancy. In low- and
middle-income countries where breastfeeding is common
and access to PMTCT services can be problematic, MTCT
rates can be as high as 25-48%.
Ensuring ART adherence is a major public health concern in
both high-and low-income countries. Virologic and clinical
success depend on good adherence, and in its absence,
HIV quickly develops therapy-limiting drug resistance.
Adherence is particularly important in pregnant and lactating
women. In addition to non-adherence increasing viral failure
risk, maternal HIV progression and development of drug
resistance, there may be increased MTCT risk. Data on ART
adherence during pregnancy are limited, and no systematic
review of ART adherence in pregnancy has been published.
These data are critical especially now that there is a global
movement towards use of triple ARV prophylaxis during
pregnancy and breastfeeding for PMTCT.
To estimate the proportion of women with adequate
ART adherence levels
postpartum in low-, middle- and high-income countries.
during pregnancy and
The US National Institutes for Allergy and Infectious Disease-National Institutes of Health (NIAID-
NIH), Division of AIDS (DAIDS): R01 AI005535901 and K23 AI 068582-01 (JBN); The US NIH-
Fogarty International Center (FIC)/Health Resources and Services Administration (HRSA)/US
President Emergency Plan for AIDS Relief (PEPFAR) Grant Award, T84HA21652-01-00 for Medical
Education Partnership Initiative (MEPI) (JBN).
Jean B. Nachega, MD, PhD, Johns Hopkins University Bloomberg School of
Public Health, Department of International Health, Global Disease Epidemiology
and Control Program; 615 N. Wolfe Street, Suite W5031, Baltimore, MD 21205,
USA; Tel: 410-955-2378; Fax: 410-502-6733; E-mail: firstname.lastname@example.org
Types of studies: all studies (cross-sectional, cohort, randomised
controlled trials) that reported ART adherence rates as a primary
or secondary outcome. Types of participants: HIV-infected
pregnant women on ART during antenatal or postnatal period or
both. Types of interventions: any type of ART. Outcome
measures: adherence rates regardless of measures (such as
self-reported, pill count, etc.).
PubMed, EMBASE, SCI Web of Science, NLM Gateway and
Of 72 eligible articles, 51studies involving 20,153 HIV-infected
pregnant women were included. Most 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 ART
adherence 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%, I2=97.7%, Figure 1) of
women 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 the postpartum (53.0%, 95% 32.8% to 72.7%) period
(p=0.005) (Figure 2).
Figure 2: Pooled proportion of pregnant women to ART, by subgroups
Figure 1: Pooled proportion of pregnant women to ART