NNRTI Ineffective Among Patients With Pretreatment HIV Drug Resistance

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Authors conducted a systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating NNRTI-based ART.

In regions with a high level of pretreatment HIV drug resistance (PDR) due to the use of antiretroviral therapy (ART), nonnucleoside reverse transcriptase inhibitors (NNRTIs) should be avoided, according to findings from a systematic review and meta-analysis published in The Journal of Infectious Diseases.

Investigators searched publication databases for papers relating to PDR with ART among individuals living with HIV. The investigators defined PDR as at least 1 HIV drug resistance mutation, nonnucleoside reverse transcriptase inhibitor (NNRTI) PDR as at least 1 mutation causing resistance to NNRTIs, and virological failure as viral load of at least 1000 copies/mL.

The final dataset included 29 cohort studies and 3 case-control studies comprising 31,441 patients. For the outcome of viral failure, investigators determined that these studies had significant publication bias (Egger test b, 2.69; standard error, 0.364; P <.001).

Of the studies (n=30) which investigated PDR on virological failure among patients receiving NNRTI therapies, risk for virological failure was higher among patients with PDR (odds ratio [OR], 3.07; 95% CI, 2.40-3.94). This increased risk was observed among both adults (n=25 studies; OR, 2.78; 95% CI, 2.19-3.53) and children (n=5 studies; OR, 7.47; 95% CI, 2.12-26.41) with significant study heterogeneity (I2, 64.8; P <.001).

The occurrence of new mutations leading to resistance was more likely to occur among patients who had PDR with NNRTI-based ART initiation than those without (n=2 studies; OR, 2.45; 95% CI, 1.70-3.52).

Of the studies (n=8) which investigated PDR on virological failure among patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), risk was for failure was increased among patients with PDR or NNRTI PDR (OR, 3.77; 95% CI, 1.96-7.28).

This study may have been limited by the inability to assess single vs dual class resistance, though the information was not available.

These data indicated that risk for virological failure was increased among individuals with PDR or NNRTI PDR, likely making NNRTI therapy ineffective among these patient populations. These results informed the 2019 guidelines from the World Health Organization.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Bertagnolio S, Hermans L, Jordan MR, et al. 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. J Infect Dis. Published online November 17, 2020. doi:10.1093/infdis/jiaa683.