CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: Of the 18 HCs with analyzable viral decay results, 14 (78%) had entry iSCA values ≥0.4 cp/mL and were included in estimation of phase 1 viral decay; 7 (39%) had sufficient detectable iSCA results for estimation of phase 2 viral decay. The median pre-ART VL by iSCA was 81 cp/mL for the HCs and 56,550 cp/mL for the NCs. There was a strong correlation between HIV RNA measurements by the iSCA and Abbott assays (Spearman r=0.90). Phase 1 viral decay did not differ between HCs and NCs (median 0.58 vs. 0.66 log10 cp/day, P=0.81). Phase 2 decay rates were significantly shorter in HCs compared to NCs (0.069 vs. 0.040 log10 cp/day, P=0.04), corresponding to a half-life of 10 vs. 17 days. Twelve weeks after ART initiation, 94% of HCs had iSCA VLs <0.4 cp/mL. No significant changes in soluble markers of inflammation were detected after 12 weeks of ART. Conclusion: The viral decay results reveal the extremely low numbers of medium- and long-lived HIV-expressing cells in ART-treated HCs. Furthermore, the second phase decay rates suggest differences in the composition or turnover of the cellular populations supporting active viral replication between HCs and NCs. These findings highlight potential directions for future HIV reservoir studies. 326 PEGYLATED IFN-ALPHA-2B DECREASES LATENT HIV MEASURES IN ART-SUPPRESSED SUBJECTS Livio Azzoni 1 , Emmanouil Papasavvas 1 , Nicolas Chomont 2 , Qingsheng Li 3 , Bonnie J. Howell 4 , Douglas D. Richman 5 , Pablo Tebas 6 , KaramMounzer 7 , Jay Kostman 8 , Luis Montaner 1 1 Wistar Inst, Philadelphia, PA, USA, 2 Univ de Montréal, Montreal, QC, Canada, 3 Univ of Nebraska, Lincoln, NE, USA, 4 Merck & Co, Inc, West Point, PA, USA, 5 Univ of California San Diego, La Jolla, CA, USA, 6 Univ of Pennsylvania, Philadelphia, PA, USA, 7 Philadelphia FIGHT, Philadelphia, PA, USA, 8 Philadelphia FIGHT Community Hlth Cntrs, Philadelphia, PA, USA Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Poster and Themed Discussion Abstracts

327 EFFECTS OF PEG-IFNΑ ON THE HIV-1 DNA LEVELS IN HIV-1/HCV COINFECTED INDIVIDUALS Victoria P. Strouvelle , Valentina Vongrad, Dominique L. Braun, Yik Lim Kok, Roger Kouyos, Karin Metzner, Huldrych F. Günthard, for the Swiss HIV Cohort Study Univ of Zürich, Zürich, Switzerland Background: Studies exploring effects of PEG-IFNα (pIFNα) on total HIV-1 DNA levels in HIV-suppressed patients have varied; therefore in a retrospective longitudinal study we assessed the effects of pIFNα on HIV-1 DNA levels in PBMC from Swiss HIV Cohort Study patients. Methods: Patients inclusion criteria were: 1. HIV-1/HCV co-infected, 2. on ART, 3. virally suppressed (< 50 HIV-1 RNA copies/ml of plasma) for ≥6 months, and 4. treated with pIFNα for ≥24 weeks. Samples were collected before, during, and post pIFN treatment (all follow-up time points available). Patients were categorised into three groups: Chronic HIV infection (n=22), Acute HIV infection (n=8), and a control group of no ART during pIFNα treatment (n=10). Patients with >1 pIFNα treatment were also included in the chronic group (n=4). HIV-1 DNA from HIV-1/HCV co-infected patients was quantified by an in-house qPCR assay measuring the U3-R region of the HIV-1 LTR. Clinical data were assessed for the effects of IFNα on the HIV-1 viral load (VL), lymphocyte and CD4 cell populations. Wilcoxon matched-pairs signed rank test was applied to all data sets to investigate significance. Results: A total of 247 samples were quantified for HIV-1 DNA with a mean number of time points (range) of 6.6 (2-12) in chronic, 5.6 (2-10) in acute and 5.7 (3-9) in the no ART groups. Maximum follow-up time was 112 months post-pIFNα. Patients were all Caucasian, mainly male (90%) with a mean age of 42 yrs. (27-55) and infected with HIV-1 subtype B (92.5%). pIFNα treatment caused general and CD4-lymphopenia in all patients as previously described. All ART treated patients maintained an undetectable VL. In non-ART- treated patients, pIFNα treatment decreased the HIV viral load by 0.89 log on average. Pre-IFNα HIV-1 DNA levels were on average 0.66 log higher in the chronic vs. the acute group. Total HIV-1 DNA levels remained stable before, during, and after pIFNα treatment with no clear trend found to suggest an effect of pIFNα on HIV-1 DNA levels in PBMCs (Figure 1). Repeated IFNα administration did not have an additional effect on HIV-1 DNA levels in the four patients studied.

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