Higher HIV viral load prior to antiretroviral therapy (ART) initiation is associated with a shorter time to viral rebound after analytic treatment interruption (ATI), according to study findings published in Med.
Data for this study were sourced from the RV254 trial, which was conducted in Thailand among patients with HIV infection who were observed for 2 to 15 years after ART initiation. In this study, researchers sought to identify biomarkers that may predict time to HIV viral rebound following ATI among patients (N=67) who were virologically suppressed via ART for a median of 3.1 years.
Among patients included in the study, 27 received no intervention, 9 received vorinostat/hydroxychloroquine/maraviroc (VHM), 18 received a therapeutic HIV Ad26/MVA mosaic vaccine regimen, and 13 received broadly neutralizing human monoclonal antibody treatment with VRC01. Of all patients, 95.5% were Thai, 97% were men, 94% were men who have sex with men (94%), 73.2% were infected with HIV subtype CRF01_AE (73.2%), and the median age was 27 (IQR, 25-32) years.
After ATI, the time to viral rebound, defined as an HIV viral load of at least 1000 copies/mL, did not differ significantly on the basis of treatment type (P =.28). However, patients who received VRC01 had a significantly delay in the time to viral rebound compared with those who received no intervention (P =.027).
No significant difference in the time to viral rebound was observed on the basis of patients’ Fiebig stage (P =.5).
Time to viral rebound was correlated with HIV viral load at the time of diagnosis (P =.022), time to virologic suppression after ART initiation (P <.001), and viral load area under the curve (AUC; P =.026). Using Kaplan-Meier survival curves, a cutoff of 4.7 log10 copies/mL was optimal for identifying patients with shorter vs longer times to viral rebound (P =.011). Other variables that significantly differentiated patients with shorter vs longer times to viral rebound included a viral load AUC cutoff of 5.8 log10 copies/mL (P =.011), a CD4 count of 326 cells/mm3 prior to ART initiation (P =.024), and a time to virologic suppression of 12 weeks following ART initiation (P =.008).
These results were corroborated when HIV viral rebound was defined as a HIV viral load of at least 20 copies/mL.
In sensitivity analyses, the cutoff for total viral load AUC was not significant when the Ad26/MVA group was removed (P =.067). In addition, CD4 cell counts prior to ART initiation were also no longer a significant predictor of time to viral rebound after the exclusion of patients who received VHM (P =.137), nor when both those who received VHM or Ad26/MVA were excluded (P =.067).
This study was limited by its small sample size, and the results may not be generalizable to other patient populations.
According to the researchers, this study “emphasizes that clinical parameters during acute [HIV infection] have long-term consequences on rebound kinetics for individuals who initiated ART early and underwent treatment interruption on average 3 years later.”
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Mdluli T, Li Y, Pinyakorn S, et al. Acute HIV-1 infection viremia associate with rebound upon treatment interruption. Med. 2022;S2666-6340(22)00276-8. doi:10.1016/j.medj.2022.06.009