Evaluation Of The Eficacy Of Integrase Inhibitor Regimens For Treatment Of HIV/AIDS Patients In Yunnan Province

Objectives:To evaluate the safety and efficacy of DTG and RAL regimens containing integrase inhibitors（INSTIs）for 48 weeks in adult HIV-1 patients.Methods:Using a retrospective cohort study,148 HIV/AIDS patients treated with an INSTIs-containing regimen in Yunnan Provincial Infectious Disease Hospital from January2008 to January 2019 were used as the study subjects.According to different antiviral treatment regimens,they were divided into the DTG regimen group and the RAL regimen group.For all enrolled cases,their baselines during the 48-week ART course and 4 weeks,8weeks,12 weeks,24 weeks,and 48 weeks after treatment were analyzed Of changes in blood routine,blood lipid and blood glucose,and liver and kidney function indexes.The main observational endpoint of virological indicators was the proportion of patients with HIV-1RNA<50 copies/m L at 48 weeks.For all patients enrolled as an intention-to-treatmen analysis,follow-up protocol analysis was performed on the patients who completed the follow-up of the experimental protocol.The main observation endpoint of immunological indicators was the change trend of CD₄⁺T/CD₈⁺T,CD₄⁺T lymphocyte count and CD₄⁺T%at 48 weeks,and the difference in time required between the two programs CD₄⁺T/CD₈⁺T≥1,CD₄⁺T lymphocyte count>500 and CD₄⁺T%≥29%.All patients were monitored for adverse reactions recorded within 48 weeks,and the incidence and reasons for discontinuation of INSTIs.Finally,resistance sites and drug susceptibility analysis were performed in non-INSTIs-associated drug-resistant populations who failed treatment during ART.Results:According to the inclusion and exclusion criteria,a total of 148 patients were eligible for the study,91 of whom used the RAL protocol at baseline and 57 patients used the DTG protocol.1.During the 48-week ART procedure,similar efficacy was detected in the two regimens in terms of blood lipids,blood routine and liver and kidney function.2.The proportion of patients with HIV-1<50 copies/m L at the 48-week period was in the PP group and the ITT group,respectively.（ITT:DTG program group accounted for 82%,RAL program group accounted for 71%;PP:DTG program group accounted for 84%,RAL program group accounted for 82%）,DTG group and RAL group at 48 weeks HIV-1<50 copies/m L.There was no significant difference in the HIV-1<50 copies/m L level between the DTG group and the RAL group at 48 weeks（c2=3.406,P=0.065）.3.48 weeks immunological indicators reached CD₄⁺T cell count>500 cells/u L,CD₄⁺T%>29%,the proportion of CD₄⁺T/CD₈⁺T>1 in DTG group was 20.12%,RAL group was 18.25%,adjusted The difference was-0.021（95%CI:-0.564～0.502,P=0.824）,and there was no significant difference between the two groups.4.Common adverse reactions were central nervous system symptoms,with 14%in the DTG group and 13%in the RAL group;followed by gastrointestinal side effects,11%in the DTG group and 12%in the RAL group.In the analysis of risk factors for the replacement regimen due to central nervous system toxicity,the risk of discontinuation was lower in the RAL group compared with the DTG group（HR:0.44,95%CI:0.21-0.95,P=0.036）.5.Of the 16 patients treated with ART,non-INSTIs resistance occurred,of which 6 were subtype C,5 were CRF01＿AE,3 were CRF07＿BC,1 was CRF08＿BC,and 1 was subtype B.Among any NRTIs mutations,K70R accounted for 70.6%and M184V accounted for 62.5%.Of the NNRTIs mutations,the most common were 179D for 35.3%and 227L for 35.3%,followed by K103N for 29.4%.Conclusions:1.Patients treated with the DTG regimen and the RAL regimen showed similar viral suppression rates at 48 weeks,and starting ART as early as possible was more conducive to inhibiting HIV-1 replication.2.The DTG and RAL schemes have similar changes in HIV patients with antiviral treatment within 48 weeks.DTG has a significant effect on blood lipids and renal function,while RAL has a significant effect on liver function.When choosing any treatment with DTG or RAL,blood lipids,liver and kidney functions should be regularly tested.3.Although compared with RAL,neuropsychiatric symptoms in patients in the DTG group are indeed more common.But in general,these adverse reactions are still relatively rare.Regular monitoring of patients during ART is important for early detection of neurotoxicity.If DTG has neuropsychiatric side effects,switching to another INSTIs or PIs can still effectively inhibit viral replication.