Abstract
BACKGROUND: 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. METHODS: Two 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. RESULTS: The total HIV-1 DNA rapidly decreased from baseline [median = 3.00 log(10) copies/10(6) peripheral blood mononuclear cells (PBMCs)] to week 24 (median = 2.55 log(10) copies/10(6) 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/10(6) PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log(10) copies/10(6) 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%. CONCLUSIONS: Baseline 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.