CROI 2016 Abstract eBook

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Oral Abstracts

26LB Effect of Sequential Vacc-4x/GM-CSF Immunization and Romidepsin on the HIV Reservoir Steffen Leth 1 ; Jesper Højen 1 ; Mariane Schleimann 1 ; Sara Nissen 1 ; Alejandra Mørk 2 ; Maja Sommerfelt 2 ; Lars Østergaard 1 ;Thomas Rasmussen 1 ; MartinTolstrup 3 ; Ole S. Søgaard 3 1 Aarhus Univ Hosp, Aarhus, Denmark; 2 Bionor Pharma, Oslo, Norway; 3 Aarhus Univ Hosp, Aarhus Nord, Denmark Background: Immune priming prior to reversal of latency may facilitate killing of infected CD4+ T cells and could be a component of an HIV cure. To clinically assess this concept, we evaluated whether therapeutic HIV immunization followed by latency reversal would impact measures of viral transcription, plasma viremia, and reservoir size in HIV patients on suppressive antiretroviral therapy (ART). Methods: This single-arm phase Ib/IIa trial enrolled 20 HIV-infected adults who received 6 intradermal immunizations with Vacc-4x adjuvanted with GM-CSF prior to receiving intravenous romidepsin 5 mg/m 2 once weekly for 3 weeks while maintaining ART. This “shock & kill” approach was followed by a monitored antiretroviral pause (MAP). Co-primary endpoints were changes from baseline in total HIV DNA in CD4+ T cells (by ddPCR) and infectious units per million ([IUPM] by quantitative viral outgrowth assay [qVOA]) as markers of the reservoir size. HIV transcription was quantitated by cell-associated unspliced HIV RNA in CD4+ T cells. Plasma HIV RNA was analyzed by the Cobas Taqman assay. Safety was evaluated at each study visit. Results: Seventeen of 20 enrolled participants (3 females, 17 males, median age 48.5 years, median CD4 670 cells/mm 3 ) completed all Vacc-4x/GM-CSF immunizations and romidepsin infusions. Reductions in the latent reservoir were observed with both assays. Total HIV DNA was reduced by 40% (95% CI: 11–59, p=0.012). qVOA was evaluable at baseline and at least one follow-up time point in 6/17 participants. The 6 evaluable participants had a median reduction in IUPM of 40% (p=0.019). As previously observed, HIV transcription increased rapidly within the first hours after each romidepsin administration. Eight participants had at least one quantifiable plasma HIV RNA (range: 21–619 c/ml) during the romidepsin infusion period. Median time from interrupting ART to plasma HIV RNA>50 copies/ml during the MAP was 14 days. Three SAEs were observed, none related to study therapy. A total of 141 AEs in 20 participants were recorded, 133 grade 1, five grade 2 and three grade 3. None of the grade 3 AEs were related to study medications. Conclusions: This is the first reported dual intervention designed to target the HIV reservoir. We used Vacc-4x/GM-CSF therapeutic HIV immunization prior to romidepsin treatment and found a significant reduction in the latent HIV reservoir. These results may serve as a benchmark for further optimization of this strategy. 27 A Patient Navigation/Contingency Management RCT for Hospitalized HIV+ Substance Users Lisa R. Metsch 1 ; Daniel J. Feaster 2 ; Lauren Gooden 3 ; Moupali Das 4 ;TimMatheson 5 ; Maxine L. Stitzer 6 ; Mamta K. Jain 7 ; Allan Rodriguez 2 ; Raul Mandler 8 ; Carlos del Rio 9 1 Columbia Univ Mailman Sch of PH, New York, NY, USA; 2 Miller Sch of Med, Univ of Miami, Miami, FL, USA; 3 Columbia Univ Mailman Sch of PH, Miami, FL, USA; 4 Gilead Scis, Inc, Foster City, CA, USA; 5 San Francisco Dept of PH, San Francisco, CA, USA; 6 Johns Hopkins BayviewMed Cntr, Baltimore, MD, USA; 7 Univ of Texas Southwestern Med Cntr, Dallas, TX, USA; 8 Natl Inst on Drug Abuse, NIH, Rockville, MD, USA; 9 Emory Univ Sch of Med, Atlanta, GA, USA Background: HIV-infected substance users are less likely to be virally suppressed due to lower rates of adherence to treatment and engagement in care. We tested the impact of patient navigation (PN) and contingency management (CM) on increasing viral suppression (<200 copies/µL) in HIV-infected substance users who were poorly engaged in care Methods: Project Hope (CTN0049) is a completed 3-arm RCT to test 6 months of PN and PN+CM versus treatment as usual (TAU) on increasing 12-month viral suppression rates. The PN arm included up to 11 sessions in which navigators motivated participants to attend HIV care and substance use treatment and provided instrumental support including making and attending appointments with participants. PN+CM added contingency management; participants could earn up to $1,160 for target behaviors including attending HIV care visits, picking up medications, attending substance use treatment, providing drug-free urines, and achieving viral suppression. Differences in viral suppression at 12 months, the primary outcome, were tested by treatment arm using intention-to-treat analysis with generalized estimating equations for binary outcomes. Results are final. Results: 801 HIV-infected out of care substance users were recruited from 11 hospitals in the US between July 2012 and January 2014. The sample was predominately male (68%), black (78%) and middle aged (m=44, SD=10). Participants reported use of stimulants (81%), marijuana (55%), high levels of alcohol (49%) and opioids (26%). Median CD4 count was 109. Viral suppression at baseline was similar across arms (PN=11%, PN+CM=10%, TAU=11%, p=.930).The percentage of patients attending at least 6 PN sessions was 74% in PN and 90% in the PN+CM arms. Average payment to an incentivized PN+CM participant was $668. Viral suppression at 12 months, available for 752 (94%), was not different across the 3 arms (PN=36%, PN+CM=38%, TAU=34%, p=.311). In secondary analyses, viral suppression (PN=39%, PN+CM=46%, TAU=35%, p(PN+CM vs TAU)=.038) and attendance at an HIV care visit (PN=79%, PN+CM=87%, TAU=69%, p(PN vs TAU)=.003); p(PN+CM vs PN)=.014) at 6 months were significantly different between arms. Conclusions: PN and PN+CM had improved indicators of HIV care in the short run, but these improvements are transitory and did not persist. At the primary 12 month assessment, neither PN nor PN+CM had any impact on viral suppression in this sample of difficult to treat, substance using, unsuppressed HIV positive individuals recruited in the hospital.

Oral Abstracts

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CROI 2016