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Meta-Analysis
. 2019 Jun 17;6(6):CD012962.
doi: 10.1002/14651858.CD012962.pub2.

Rapid initiation of antiretroviral therapy for people living with HIV

Alberto Mateo-Urdiales  1 , Samuel Johnson, Rhodine Smith, Jean B Nachega, Ingrid Eshun-Wilson
Affiliations
Meta-Analysis

Rapid initiation of antiretroviral therapy for people living with HIV

Alberto Mateo-Urdiales et al. Cochrane Database Syst Rev. .

Abstract

Background: Despite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low-and-middle-income countries. High rates of loss to follow-up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow-up, improve virological suppression rates, and reduce mortality.

Objectives: To assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies.

Search methods: We searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts.

Selection criteria: We included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion.

Data collection and analysis: Two review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta-analysis. We assessed the certainty of the evidence using the GRADE approach.

Main results: We included seven studies with 18,011 participants in the review. All studies were carried out in low- and middle-income countries in adults aged 18 years old or older. Only one study included pregnant women.In all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART.Comparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate-certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate-certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low-certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low-certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low-certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events.

Authors' conclusions: RCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low- and middle-income settings. The studies demonstrating these effects delivered rapid ART combined with several setting-specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems.

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Conflict of interest statement

AMU has no known conflicts of interest. SJ has no known conflicts of interest. RS has no known conflicts of interest. JBN has no known conflicts of interest. IEW has no known conflicts of interest.

Figures

1
1
Conceptual model of factors influencing the HIV care continuum
 ART: antiretroviral therapy, IRIS: immune reconstitution inflammatory syndrome; PLWH: people living with HIV
2
2
Study flow diagram
3
3
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies
4
4
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study
5
5
Forest plot of comparison 1. Rapid ART versus standard care, outcome 1.1, mortality
6
6
Forest plot of comparison 1. Rapid ART versus standard care, outcome 1.2, virological suppression at 12 months
1.1
1.1. Analysis
Comparison 1 Rapid ART versus standard care, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Rapid ART versus standard care, Outcome 2 Virological suppression at 12 months.
1.3
1.3. Analysis
Comparison 1 Rapid ART versus standard care, Outcome 3 Retention in care.
1.4
1.4. Analysis
Comparison 1 Rapid ART versus standard care, Outcome 4 Uptake of ART at 90 days.
1.5
1.5. Analysis
Comparison 1 Rapid ART versus standard care, Outcome 5 Uptake of ART at 12 months.
1.6
1.6. Analysis
Comparison 1 Rapid ART versus standard care, Outcome 6 Treatment modification.
2.1
2.1. Analysis
Comparison 2 Rapid ART versus standard care: subgroup analysis by time of ART initiation, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 Rapid ART versus standard care: subgroup analysis by time of ART initiation, Outcome 2 Virological suppression at 12 months.
2.3
2.3. Analysis
Comparison 2 Rapid ART versus standard care: subgroup analysis by time of ART initiation, Outcome 3 Retention in care.
2.4
2.4. Analysis
Comparison 2 Rapid ART versus standard care: subgroup analysis by time of ART initiation, Outcome 4 Uptake of ART at 90 days.
2.5
2.5. Analysis
Comparison 2 Rapid ART versus standard care: subgroup analysis by time of ART initiation, Outcome 5 Uptake of ART at 12 months.
3.1
3.1. Analysis
Comparison 3 Rapid ART versus standard care, virological suppression: analysis by method of measurement, Outcome 1 Virological suppression at 12 months in participants on ART for at least 6 months.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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