Pegylated interferon (Peg-IFN)-α2a resulted in viral suppression and reduction in integrated proviral HIV DNA in 9 of 20 ART-suppressed subjects undergoing analytical ART interruption (ATI; NCT00594880). Here we evaluated if Peg-IFN-α2b, in the presence of HIV reactivation (ATI), would be safe, maintain viral suppression during ATI and decrease latent viral reservoir in chronic HIV infection.
20 individuals with well controlled HIV infection (on ART, VL <50 copies/ml) received weekly 1 μg/kg Peg-IFN-α2b sc for 20 weeks, with a 4 week ATI (weeks 5-9 of IFN treatment). In addition to safety monitoring, HIV measures (see Table 1) were assessed at baseline and week 20. Final statistical analysis: we used Wilcoxon Signed rank test to test differences between time points; exact Fisher tests to compare frequency of viral suppression during ATI; Spearman tests, mixed effect models and hierarchical clustering to test relationships between HIV reservoir measurements.
At completion study participants were 20% females, 70% AA. Median age was 47. 18 subjects completed treatment (2 early terminations) with 7 serious events (neutropenia). Peg-IFN-α2b suppressed plasma HIV RNA during the 4 week ATI in 52% (95% CI= 32-73%), similar to NCT00594880 and higher than historical controls (13%; 95% CI= 3-36%, p= 0.0127; NCT00051818) At week 20, we observed a significant reduction in HIV RNA-expressing GALT cells (p= 0.012) and a reduction in integrated HIV DNA in circulating CD4s (p= 0.0797). Other markers did not change significantly. However, higher baseline levels of rectal mucosa RNA, integrated DNA, TILDA, p24 and 2LTR were associated with a greater decrease after the intervention. Reservoir measurements were weakly correlated at baseline and their changes over time did not correlate to one another. Amount of HIV rebound during the 4-week ATI was not associated with a change in reservoir measures.
Treatment with Peg-IFN-α2b (20 weeks, 4-week ATI) 1) is safe and well tolerated, 2) maintains viral suppression during a 4-week ATI in half of the subjects and 3) is associated with significant decrease of rectal mucosa HIV RNA and a decrease trend in integrated HIV DNA (PBMC) Randomized studies incorporating an ART-only arm, repeated sampling and multiple latent reservoir assessments, such as our ongoing NCT02227277, should allow to conclusively interpret the reduction in HIV reservoir measures observed in subjects with high baselines and confirm our pilot study observations.