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Meta-Analysis
. 2021 Aug 2;224(3):377-388.
doi: 10.1093/infdis/jiaa683.

Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis

Silvia Bertagnolio  1 , Lucas Hermans  2   3 , Michael R Jordan  4   5   6 , Santiago Avila-Rios  7 , Collins Iwuji  8 , Anne Derache  9 , Eric Delaporte  10 , Annemarie Wensing  2   3 , Theresa Aves  11 , A S M Borhan  11 , Alvin Leenus  11 , Neil Parkin  12 , Meg Doherty  1 , Seth Inzaule  1 , Lawrence Mbuagbaw  11
Affiliations
Meta-Analysis

Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis

Silvia Bertagnolio et al. J Infect Dis. .

Abstract

Background: Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC).

Methods: We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR).

Results: Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR.

Conclusions: This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization's recommendation to avoid using NNRTIs in countries where levels of PDR are high.

Keywords: ART; HIV drug resistance; NNRTIs; pretreatment HIV drug resistance; treatment failure; virological failure.

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Figures

Figure 1.
Figure 1.
Study selection procedure. Abbreviations: ART, antiretroviral therapy; NNRTI, nonnucleoside reverse transcriptase inhibitor.
Figure 2.
Figure 2.
Summary of risk of bias of included studies.
Figure 3.
Figure 3.
Risk of virological failure (VF) among people with pretreatment HIV drug resistance (PDR) compared to people without PDR initiating NNRTI-based antiretroviral therapy. The dotted vertical line represents the overall risk of VF if PDR is present. The open diamond represents the overall risk of VF if PDR is present. Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 4.
Figure 4.
Risk of virological failure (VF) among people with NNRTI pretreatment HIV drug resistance (PDR) compared to people without PDR initiating NNRTI-based regimens. The dotted vertical line represents the overall risk of VF if NNRTI PDR is present. The open diamond shows the confidence intervals of the overall risk of VF if NNRTI PDR is present. Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 5.
Figure 5.
A, Risk of acquisition of new resistance mutations in people with pretreatment HIV drug resistance (PDR) compared to people without PDR initiating NNRTI-based regimens. B, Risk of HIV treatment discontinuation or switch among people with pretreatment HIV drug resistance (PDR) compared to people without PDR initiating NNRTI-based regimens. Abbreviations: CI, confidence interval; OR, odds ratio.
Figure 6.
Figure 6.
Risk of virological failure in patients with NNRTI pretreatment HIVDR (PDR) compared to those without PDR receiving efavirenz in combination with lamivudine/emtricitabine and tenofovir. Abbreviations: CI, confidence interval; OR, odds ratio.
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References

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    1. World Health Organization. Surveillance of HIV drug resistance in adults initiating antiretroviral therapy.http://www.who.int/hiv/pub/drugresistance/pretreatment_drugresistance/en/. Accessed 10 January 2020.
    1. World Health Organization. Guidelines on the public health response to pretreatment HIV drug resistance. https://bit.ly/2C5GI7T. Accessed 15 August 2019.

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