A study of adherence to antiretroviral therapy and its effect on the risk of HIV-1 resistance in patients with virological failure
Authors:   Novosibirsk State Medical University, Novosibirsk, Russia, Kapustin D.V. ,   City Infectious Diseases Clinical Hospital No. 1, Novosibirsk, Russia, Krasnova E.I. ,   Novosibirsk State Medical University, Novosibirsk, Russia; City Infectious Diseases Clinical Hospital No. 1, Novosibirsk, Russia, Khokhlova N.I. ,   Novosibirsk State Medical University, Novosibirsk, Russia; City Infectious Diseases Clinical Hospital No. 1, Novosibirsk, Russia, Nalimova T.M. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Kriklivaya N.P. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Khalikov M.R. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Totmenin A.V. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Gotfrid L.G. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Gashnikova M.P. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Gashnikova N.M. ,   State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russia, Kuznetsova V.G. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Pozdnyakova L.L. ,   City Infectious Diseases Clinical Hospital No. 1, Novosibirsk, Russia, Kolpakova T.A. ,   Novosibirsk State Medical University, Novosibirsk, Russia, Poddubnaya L.V. ,   Novosibirsk State Medical University, Novosibirsk, Russia
Published: August 2024

Introduction. Over the past 10 years, there has been an increase in HIV-1 resistance to antiretroviral drugs worldwide. HIV infection patients with low adherence to antiretroviral therapy (ART) are most often at risk of developing acquired HIV-1 resistance. The identification of key factors affecting the degree of adherence will allow timely detection of patients with a high risk of poor adherence to ART and treatment defaulting, and develop individual management tactics for such patients to reduce the risk of resistance development. Aim. To study the factors influencing adherence to ART in patients with virological failure and the effect of adherence on the risk of developing acquired HIV-1 resistance to first-line antiretroviral drugs. Materials and methods. Two hundred and seventy one patients with an confirmed diagnosis of HIV infection, with different stages of the disease, aged 21 to 59 years, who were followed-up from March 2018 to August 2022 at the Center for the Prevention and Control of AIDS (City Infectious Clinical Hospital No. 1, Novosibirsk) and received ART, were enrolled in a study. The criterion to include patients in the study was a virological breakthrough during previously effective ART with first-line drugs (when an undetectable level of HIV RNA load was recorded for 3–6 months). A retrospective analysis of the degree of adherence to ART of the studied patients with HIV infection and virological breakthrough was performed, considering various factors. The HIV-1 drug resistance testing was carried out based on the State Research Center of Virology and Biotechnology VECTOR. Results. Men predominated among the patients – 56.4% (n = 153). The average age was 35.4 ± 2.85 years. Heterosexual transmission of HIV was dominant – 64.8%. Parenteral transmission of HIV (intravenous drug abuse) accounted for 31.5% of cases. According to the results of the retrospective analysis of the degree of adherence to ART, it was found that 48.3% (131 out of 271) of patients had missed medications, including low adherence in 31.7% (86 out of 271) patients; average – in 16.6% of patients (45 out of 271). Most often, poor adherence was reported in people with parenteral HIV transmission– 75.3% compared with sexual transmission – 36% (p < 0.001), and in rural residents – 62.5% compared with urban residents – 34.1% (p < 0.001). Among men, missed medication was detected more often than in women – 57.5 and 36.4%, respectively (p < 0.001). Also, a significant factor was the lack of permanent employment – poor adherence was in 69.5% of patients in this group compared with patients having permanent employment – 26.3% (p < 0.05). On the contrary, high adherence was more often observed in female patients – 63.6% compared with male ones – 42.5%; in the presence of permanent employment – 73.7% compared with 30.5% in it’s absence; in the case of sexual transmission – 64.0% compared with parenteral transmission – 24.7%; in urban residents – 65.9% versus 37.5% in rural residents (p < 0.05). According to the totality of all mutations revealed, HIV drug-resistant variants were found in 54.6% of the patients with virological ART failure (148 out of 271). Of the 148 HIV-1 drug-resistant variants, a combination of drug resistance mutations from the group of nucleoside reverse transcriptase inhibitors (NRTIs) was most often detected and non-nucleoside reverse transcriptase inhibitors (NNRTIs) – in 60.1% (89 cases). Isolated mutations to NRTIs were found in 15.5% (23) cases, for NNRTIs – in 12.2% (18). A combination of mutations of resistance to NRTIs + integrase inhibitors (IIs) was found in 4.1% (6) patients. The proportion of patients with resistance to NRTIs and PIs (protease inhibitors) was 2% (3); to NRTIs + IIs – 1.4% (2). A combination of mutations to three classes of drugs at once was detected in 6 patients: NRTIs + NNRTIs + IIs – 2.7% (4) and NRTIs + NNRTIs + PIs – 1.4% (2). An isolated mutation to IIs was in one patient (0.6%). Conclusion. The analysis showed that non-adherence was reported in a significant part of patients – 48.3% (low – 31.7%, moderate – 16.6%). Factors contributing to poor adherence to ART were: parenteral transmission of HIV (in 75.3% of people with poor adherence); living in rural areas (in 62.5%); lack of permanent employment (in 69.5%); male sex (in 57.5%). Among patients with detected HIV drug resistance (n = 148), individuals with poor adherence prevailed (70.9%) compared with patients who did not have HIV drug resistance (23.6%) (p < 0.001). Taking into account the data obtained, when choosing the initial ART regimen, it is necessary to analyze the degree of risk of non-adherence depending on social and other factors. The high frequency of registration of HIV drug-resistant mutations found in the Novosibirsk Region necessitates timely testing for drug-resistant HIV patients with virological ART failure and the introduction of screening for primary drug resistance in patients at risk of poor adherence.