Baseline Resistance to Second-Generation INSTIs, First-Line NRTIs Unlikely in HIV

Study results published in Clinical Infectious Diseases indicate a low prevalence of baseline resistance to certain antiretroviral therapy (ART) regimens among patients newly diagnosed with HIV infection in Europe.

Researchers sourced data for this study from MeditRes HIV, a consortium of centers in Portugal, Spain, France, Italy, and Greece. Patients included in the analysis were ART-naive and diagnosed with HIV between 2018 and 2021. The prevalence of surveillance drug resistance mutations and clinically relevant resistance to integrase strand transfer inhibitors (INSTIs) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs) were reported. The Standford Algorithm was used to evaluate clinically relevant resistance, defined as mutations with a resistance level of 3 or greater.

The patients (N=2705) included in the final analysis were most commonly men (72.2%); aged 30 to 50 years (45.3%); born in Europe (47.2%); and contracted HIV through homosexual intercourse (43.0%). The majority (56.3%) patients were infected with HIV subtype B (56.3%), and most patients did not have hepatitis B (71.2%) or C (75.2%) coinfection. In general, the patients had CD4 counts of 350 to 1000 cells/mm³ (36.7%) and an HIV viral load of less than 100,000 copies/mL (40.5%).

The overall prevalence of surveillance drug resistance mutations was 0.30%. For patients receiving NRTIs, resistant mutations were observed in 5.77%, of whom 3.14% had singleton mutations.

The percentage of patients with clinically relevant resistance was low overall but tended to be higher among those receiving INSTIs (2.33%) vs NRTIs (1.74%). For INSTIs, the highest rate of clinically relevant resistance was observed for raltegravir- and elvitegravir-based regimens (both 2.29%), followed by dolutegravir- and bictegravir-based regimens (both 0.15%). For NRTIs, resistance rates were highest for abacavir-based regimens (1.74%), followed by lamivudine/emtricitabine-based regimens (1.07%) and tenofovir alafenamide-based regimens (0.89%; intermediate resistance).

In regard to INSTIs, the researchers noted a discrepancy between clinically relevant resistance and surveillance drug resistance mutation rates (2.33% vs 0.30%, respectively). This was primarily due to the detection of previously unknown resistant mutations.

In a univariate analysis, age (<30 vs >50 years) was significantly predictive of higher rates of NRTI-associated surveillance drug resistant mutations (5.95% vs 2.69%; P =.0051) and clinically relevant resistance (3.15% vs 1.11% P £.0127). Female vs male sex was significantly predictive of higher rates of INSTI-associated surveillance drug resistant mutations (0.85% vs 0.20%; P =.0263), and clinically relevant resistance to second-generation INSTIs was more likely in patients infected with a non-B HIV subtype (P =.02).

Limitations of this study include that the majority of samples were sourced from Spain, France, and Italy, and interruptions in data collection and reporting due to the COVID-19 pandemic.

The researchers concluded, “[T]he evaluation of resistance data may not be an issue for rapid initiation of an INSTI first-line based regimen and can be deferred until resistance data become available.” Further evaluation is needed for rapid initiation of INSTI-based regimens for newly diagnosed individuals.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.