Abstract
BackgroundFactors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.MethodsTwo sets of study populations were included: 490 China AIDS Clinical Trial (CACT) participants (Training cohort, followed up for 144 to 288 weeks) and 117 outpatients from Peking Union Medical College Hospital (PUMCH) (Validation cohort, followed up for more than 96 weeks). All patients were chronically HIV-1-infected and achieved successful HIV-1 plasma RNA suppression within week 48. Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, 144 and 288 weeks after combined antiretroviral therapy (cART) initiation were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.ResultsThe total HIV-1 DNA rapidly decreased from baseline [median = 3.00 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (median = 2.55 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 plasma RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (< 100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.ConclusionsBaseline total HIV-1 DNA and CD4+ T cell count are two independent predictors of total HIV-1 DNA after treatment. The derived model based on these two baseline factors provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART.
Highlights
A critical goal of antiretroviral therapy is to reduce the size of the total HIV-1 DNA reservoir which poses a major obstacle for HIV-1 eradication [1,2,3]
High total HIV-1 DNA levels during combined antiretroviral therapy (cART) have been associated with faster viral rebound after structured treatment interruption (STI) [8,9,10], while low total HIV-1 DNA levels may increase the possibility of prolonged viral remission after cART interruption, which was observed in the Mississippi baby [11] and post-treatment controllers (PTCs) [12, 13]
In the VISCONTI cohort study, the median total HIV-1 DNA level was near 100 copies/106 peripheral blood mononuclear cells (PBMCs) in the 14 PTCs when cART was discontinued, which served as a milestone of relatively successful HIV1 reservoir control, potentially leading to prolonged remission or functional cure [12]
Summary
A critical goal of antiretroviral therapy is to reduce the size of the total HIV-1 DNA reservoir which poses a major obstacle for HIV-1 eradication [1,2,3]. A cross-sectional study has reported that 28% out of 522 patients who are initiated cART during the chronic phase can achieve low total HIV-1 DNA (< 150 copies/106 PBMCs) after long-term viral suppression [18]. As it is associated with ART-free remission, total HIV-1 DNA could serve as a usefully virologic parameter for monitoring therapeutic effects. Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions
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