Factors Associated With Post-treatment Control Of Viral Load In HIV-infected Patients: A Meta-analysis

Objective: The acquired immunodeficiency syndrome(AIDS)is an important public health problem affecting human health.The human immunodeficiency virus(HIV)has claimed more than 30 million lives over the past four decades.Antiretroviral therapy(ART)is one of the major medical successes of the late 20 th century.Effective ART results in indefinite viral suppression,restored immune function,improved quality of life,and reduced viral transmission.It can even bring the life expectancy of people living with HIV(PLWH)close to normal.However,this treatment still has some limitations.ART does not eliminate the viral reservoir and lifelong medication is required to maintain the viral suppression.Due to the adverse reactions of ART drugs,the economic burden of long-term drug use,and the pressure caused by social psychology,many patients cannot use ART for a lifetime.While the majority of patients receiving ART experience viral rebound shortly after treatment interruption(TI),a small percentage,called post-treatment controllers(PTCs),can maintain viral inhibition for a long time.This study aimed to investigate the factors related to maintaining viral inhibition after ART discontinuation,to find effective predictors of PTCs,and to provide a basis for the study of ART discontinuation to screen patients and for the clinical needs of long-term ART discontinuation.Methods: Articles in the Pub Med,Web of Science,Embase,and Cochrane Library databases published between January 2011 and July 2022 were searched.The main medical subject words used for the search included ‘HIV’,‘AIDS’,‘ART’,‘interruption’,and ‘PTC’.The results were imported into End Note X9 to screen references according to inclusion and exclusion criteria and extract relevant data.The bias risk assessment tools were used to assess the study quality and bias risk.The studies with available data were included in the metaanalysis,and the fixed effects model was used to combine the data.I2 was calculated to estimate the proportion of heterogeneity,and subgroup analysis was performed to determine the source of heterogeneity.Publication bias was graphically evaluated using funnel plots and Egger’s tests,the proportion(based on a single arm)was used as the effect estimate,and significance was determined using the Z-test.The meta-analysis was performed using R language 4.2.1,Stata 16.0 and Excel 2019.Results: A total of 11479 published journal articles were retrieved,and 31 articles that met the inclusion criteria were selected.The median time to viral rebound without intervention after TI was 3 weeks,ranging from 1 to 8.68 weeks.Nearly one year after TI,the median proportion of PTCs was 8.1%,ranging from 3.2% to 15.3%.The pooled proportion for of which the time to viral rebound was more than 12 weeks was 5.1%(95% CI: 3.5%~7.6%,I2 = 0%).In the subgroup analysis,factors associated with maintaining viral suppression for more than 12 weeks after TI were assessed.Individuals who started ART during the acute or early stages of HIV infection(8.7%;95% CI: 5.5~13.5%)were found to have significantly higher rates of maintaining viral suppression for more than 12 weeks after TI than those who started ART during in the chronic stage of HIV infection(2.7%;95% CI: 1.2%~5.8%).The Z-test was used to compare the proportions of the combined estimates.When Z was 2.66 at P= 0.01 < 0.05 were considered significant.The percentage of PTCs was approximately 7.2%(95% CI:5.6%~8.7%,I2 = 35.8%).No publication bias was observed in funnel plots and Egger’s test(P = 0.371>0.05).In the meta-analysis,the impact of seven factors that might be associated with PTC rates was assessed,and none showed a significant correlation with the proportion of PTC.Conclusion: In this study,about 5.1% of PLWH maintained viral suppression more than 12 weeks after TI.ART initiation in the acute or early phases can delay viral rebound after TI.No reliable indicator has been found to predict the rebound time of the virus.Many vaccines and antibodies have also been shown to be effective in prolonging viral control in people without PTC,and more research is needed to develop alternative ART therapies that can effectively inhibit or even eliminate.