CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: INSPIRE 2 was a single arm trial conducted in US and Canada. INSPIRE 3 was a two arm trial with 3:1 randomization to rhIL-7 vs. control conducted in Europe and South Africa. Participants had to be receiving ART with plasma HIV-RNA<50 copies/mL and CD4 T-cell count between 101-400 cells/ m L. Patients with chronic hepatitis B or C co-infection or active infections were excluded. R-hIL-7 was administered at 20 m g/kg, in 3 weekly s/c injections per cycle. A repeat cycle was administered if, at any quarterly evaluation, CD4 Tcells fell below 550 cells/ m L. In INSPIRE 3, participants randomized to the control arm crossed to receive r-hIL-7 if CD4 cells were below 500 cells/ m L at 12 months. Results: 111 patients were included: 23 in INSPIRE 2 and 88 in INSPIRE 3 including 24 in the control arm. They received one (107), two (74), three (14) or four r-hIL-7 cycles (1) over a median follow-up of 23 months. R-hIL-7 was well tolerated. Four grade 4 events were observed including one asymptomatic ALT elevation. After the induction cycle in INSPIRE 2 and 3 respectively, 6% and 17% developed binding antibodies against IL-7 (neutralizing in 0% and 1%). After the second cycle binding antibodies developed in 82% and 77% (neutralising in 38% and 37%) without impact on the CD4 response. 13% and 17% of patients experienced at any time HIV RNA > 200 copies/mL in INSPIRE 2 and 3, respectively. HIV DNA per CD4 T cells and per PBMC was stable over follow up. The first cycle led to a substantial increase of CD4 T cells, mainly naïve and central memory without expansion of Treg cells. Half the patients spent more than 63% of their follow-up with more than 500 CD4 T cells/ m L. The baseline CD4 level was a strong predictor of the probability of staying above 500 CD4 T cells/ m L (HR=2.2, p<.0001) whereas there was no difference between the repeated cycles (HR=.99, p=.96). Conclusions: Repeated cycles of r-hIL-7 were well tolerated and achieved sustained immune restoration over 500 CD4 T cells/ m L in the majority of study participants. 338 CRF19_cpx Is an Evolutionary Fit HIV-1 Variant Exclusively AssociatedWith Rapid Progression to AIDS in Cuba Vivian Kouri 2 ; Ricardo Khouri 1 ;Yoan Alemán 2 ;Yeissel Abrahantes 2 ; Nico Pfeifer 3 ; Andrea-Clemencia Pineda-Peña 4 ; Jorge Pérez 2 ; Lissette Pérez 2 ; KristelVan Laethem 4 ; Anne-Mieke Vandamme 4 1 Fundação Oswaldo Cruz, Salvador, Brazil; 2 Instituto Pedro Kouri, Havana, Cuba; 3 Max Planck Institute for Informatics, Saarbrucken, Germany; 4 Katholieke Universiteit Leuven, Leuven, Belgium Background: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Methods: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as >3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, coreceptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Results: Subtyping revealed 25 subtype B strains, 6 C, 7 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All CRF19 were AIDS-RP. Data mining identified CRF19, oral candidiasis and RANTES levels as strongest predictors of AIDS-RP. CRF19 was more frequently associated with CXCR4 coreceptor use, higher fitness scores in the protease region, and higher viral load at diagnosis. Patient characteristics Clinical, immunological and virological markers for the non-AIDS, chronic-AIDS and AIDS-RP groups

Poster Abstracts

1) Patient characteristics at HIV diagnosis for the non-AIDS, chronic-AIDS and AIDS-RP groups. 2) Clinical, immunological and virological markers at sampling for the three studied groups. TDR (transmitted drug resistance): NRTI resistance mutations M41L, F116Y/T215S/K219Q, M41L/T215D and D67N/T215S/K219Q; NNRTI resistance mutations twice K103N and PI resistance mutations N88DN and M46L. Data are expressed as median values with interquartile ranges, or as proportion (%) with number of patients between brackets. Statistical differences between groups were tested using Kruskal-Wallis or Chi-square test for trend. Results were considered significant at p-value<0.05 (displayed in bold). N = number of patients. Conclusions: CRF19 is a recombinant of subtype D (C-part of Gag,PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination

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CROI 2015