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Meta-Analysis
. 2013 Apr 30;2013(4):CD009153.
doi: 10.1002/14651858.CD009153.pub3.

Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

Andrew Anglemyer  1 , George W Rutherford, Tara Horvath, Rachel C Baggaley, Matthias Egger, Nandi Siegfried
Affiliations
Meta-Analysis

Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

Andrew Anglemyer et al. Cochrane Database Syst Rev. .

Abstract

Background: Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART).

Objectives: To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples.

Search methods: We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language.

Selection criteria: Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART DATA COLLECTION AND ANALYSIS: Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form.

Main results: One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350-550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I(2)=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95% CI 0.17, 0.75] with substantial heterogeneity (I(2)=62%). We also performed subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner's CD4 cell count. Among couples in which the infected partner had ≥350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples.

Authors' conclusions: ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed.Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered.

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Conflict of interest statement

None known.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Newcastle‐Ottawa Scale for Bias Assessment
3
3
Screening process, PREVIOUS version of the review (Anglemyer 2011b)
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4
Screening process, CURRENT version of the review.
5
5
Forest plot of comparison: 1 Delayed vs Immediate ART (RCTs), outcome: 1.1 Linked Incident HIV Infection.
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6
Forest plot of comparison: 1 Delayed vs Immediate ART (RCTs), outcome: 1.2 All Incident HIV Infection.
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7
Forest plot of comparison: 2 Treated with ART vs Not Treated with ART (Observational Studies), outcome: 2.1 Incident HIV Infection.
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Forest plot of comparison: 3 Treated with ART vs Not Treated with ART (Observational Studies, sensitivity analysis), outcome: 3.1 Incident HIV Infection.
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9
Forest plot of comparison: 3 Treated with ART vs Not Treated with ART (< 200, 200‐350, and > 350 CD4 Subgroup Analysis) (Observational Studies), outcome: 3.1 Incident HIV Infection.
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10
Forest plot of comparison: 5 Treated with ART vs Not Treated with ART (Female/Male Subgroup Analysis) (Observational Studies), outcome: 5.1 Incident HIV Infection.
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11
Forest plot of comparison: 5 Treated with ART vs Not Treated with ART (Subgroup Analysis: LMIC) (Observational Studies), outcome: 5.1 Incident HIV Infection.
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Forest plot of comparison: 1 Delayed vs Immediate ART (RCTs), outcome: 1.3 Severe or Life‐Threatening Adverse Events (Grade 3 or 4).
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Forest plot of comparison: 1 Delayed vs Immediate ART (RCTs), outcome: 1.4 Grade 3 or 4 Laboratory Abnormalities.
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Funnel plot of comparison: 1 Treated with ART vs Not Treated with ART (Observational Studies), outcome: 2.1 Incident HIV Infection.
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Funnel plot of comparison: 2 Treated with ART vs Not Treated with ART (Observational Studies, sensitivity analysis), outcome: 3.1 Incident HIV Infection.
1.1
1.1. Analysis
Comparison 1 Delayed vs Immediate ART (RCTs), Outcome 1 Linked Incident HIV Infection.
1.2
1.2. Analysis
Comparison 1 Delayed vs Immediate ART (RCTs), Outcome 2 All Incident HIV Infection.
1.3
1.3. Analysis
Comparison 1 Delayed vs Immediate ART (RCTs), Outcome 3 Severe or Life‐Threatening Adverse Events (Grade 3 or 4).
1.4
1.4. Analysis
Comparison 1 Delayed vs Immediate ART (RCTs), Outcome 4 Grade 3 or 4 Laboratory Abnormalities.
2.1
2.1. Analysis
Comparison 2 Treated with ART vs Not Treated with ART (Observational Studies), Outcome 1 Incident HIV Infection.
3.1
3.1. Analysis
Comparison 3 Treated with ART vs Not Treated with ART (Observational Studies, sensitivity analysis), Outcome 1 Incident HIV Infection.
4.1
4.1. Analysis
Comparison 4 Treated with ART vs Not Treated with ART (< 200, 200‐349, and ≥350 CD4 Cells/µL Subgroup Analysis) (Observational Studies), Outcome 1 Incident HIV Infection.
5.1
5.1. Analysis
Comparison 5 Treated with ART vs Not Treated with ART (Female/Male Subgroup Analysis) (Observational Studies), Outcome 1 Incident HIV Infection.
6.1
6.1. Analysis
Comparison 6 Treated with ART vs Not Treated with ART (Subgroup Analysis: Low‐/Middle‐Income vs High‐income)) (Observational Studies), Outcome 1 Incident HIV Infection.
See this image and copyright information in PMC

Update of

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Anglemyer 2011a
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