CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Results: 5,627 IN tests were linked to NYS HIV registry; 4,208 (75%) had paired PR-RT tests. 3,533 (63%) cases were stage 3 HIV infection at time of IN testing. Among the 4,626 cases where the IN test was not an initial test, 63% of first IN tests occurred ≥11 years after HIV diagnosis. Resistance to ≥1 IN drug was seen in <1% of 1,001 initial tests and in 8.6% of 4,626 non-initial tests. Among 3,415 non-initial tests for which paired PR/RT sequences were obtained, 400 (11.7%) showed IN resistance, 231 (6.8%) showed resistance to >1 drug class and 55 (1.6%) showed resistant to all drug classes. Of 3,515 newly diagnosed HIV cases in NYS in 2014, 16% had an initial IN test, compared to 55%who were tested for PR-RT. Higher rates of initial IN testing were seen among males (18%), Whites and Hispanics (19%), MSM and MSM/IDU risk (21%), and New York City residents (18%). Conclusions: Our data shows the rate of IN testing at time of diagnosis is rising but is lower than PR-RT testing, which is consistent with the recommendations. Infrequent resistance seen in the initial-test group suggests transmitted IN inhibitor resistance is not a major concern at present. Initial IN testing varies across population subgroups. Time from HIV diagnosis to IN test and percent stage 3 HIV infection in our study suggests that in this period the majority of IN-GRTs were ordered for long-standing cases at advanced stage of disease. 502 Immunologic Criteria Are Poor Predictors of Virologic Outcomes in Nigeria Nicaise Ndembi 1 ; Fati M. Ibrahim 1 ; James Okuma 1 ; Ahmad Aliyu 1 ; Samuel Peters 1 ; Charles Mensah 1 ; Alash’le Abimiku 2 ; Clement Adebamowo 2 ; Manhattan E. Charurat 3 ; Patrick Dakum 1 1 Inst of Human Virology, Abuja, Nigeria; 2 Inst of Human Virology, Univ of Maryland Sch of Med, Baltimore, MD, USA; 3 Inst of Human Virology, Baltimore, MD, USA Background: Nigeria has made significant gains in scaling-up access to HIV prevention, treatment and support services and by the end of 2014, provided antiretroviral therapy (ART) to over 747,382 individuals. The main objective of this study was to determine predictors of immunologic failure in absence of routine viral load (VL) monitoring. Methods: This was a retrospective cohort study of 12,456 HIV-infected patients enrolled into HIV care at the University of Abuja Teaching Hospital between February, 2005 and December, 2014. Immunologic failure defined as having a decrease in CD4 cell count to pretherapy baseline level (or below) or persistent CD4 levels <100 cells/mm3 after 6 months on ART. HIV genotyping was performed on a subset of patients with 2 consecutive VL measurements >1,000copies/ml. To identify predictors of immunologic failure, univariate and multivariate analyses were performed using log binomial models to estimate relative risks (RR) and confidence intervals. All statistical analyses were performed with the statistical software package SAS release 9.1 (SAS Institute Inc, Cary, North Carolina). Results: A total of 5,928 patients who initiated ART were included in the analysis. The entry point for 3,924 (66.2%) was through VCT, 3,468 (58.5%) were initiated on NVP containing regimen and 2,140 (36.1%) initiated on TDF, baseline CD4 was 268±23.7 cells/ul, and mean VL was 3.3±1.3.log10copies/ml. Among 2,602 patients with immunologic failure, 868 (33.3%) had VL measurements and 381 (43.9%) of these had a detectable VL. Fifty six samples (56/198; 28.3%) had no resistance; 160 (80.1%) harbored NRTI resistance; 151 (76.3%) M184I/V; 29 (14.6%) had ≥ 3 TAMs, and 37 (18.7%) had K65R, of which all were on TDF. One hundred and sixty-two samples (81.8%) harbored NNRTI resistance; 72 (36.4%) Y181C and 68 (34.3%) K103N with 53 % having ≥ 2 etravirine associated mutations. Service entry point [RR (95%CI): 0.79 (0.64–0.91); p<0.001]; being on NVP containing regimen [RR (95%CI): 1.21 (0.99 – 1.45); p=0.023]; WHO stage III or IV [0.76 (0.60 – 0.96); p=0.013]; baseline CD4 cell count <200cells/ul [0.19 (0.16 – 0.22); p<0.001]; male gender [1 (1.07–1.40); p=0.005] were associated with immunologic failure. Conclusions: Immunologic criteria for failure erroneously classified patients without virological replication as failing therapy in our program. Clinico-immunological monitoring without viral testing resulted in frequent unnecessary ART regimen switches and accumulation of HIV drug resistance mutations. 503 Global Tenofovir Resistance Following 1st-Line Regimens for Adult HIV-1 Infection John Gregson 1 ; MichelleTang 2 ; Nicaise Ndembi 3 ; Raph Hamers 4 ;Vincent C. Marconi 5 ; Elliot Raizes 6 ; Rami Kantor 7 ; RobertW. Shafer 2 ; Ravindra K. Gupta 8 ; for theTenoRes StudyTeam 1 London Sch of Hygiene & Trop Med, London, UK; 2 Stanford Univ, Stanford, CA, USA; 3 Inst of Human Virology, Abuja, Nigeria; 4 Amsterdam Inst for Global Hlth and Develop, Amsterdam, Netherlands; 5 Emory Univ Sch of Med, Atlanta, GA, USA; 6 CDC, Atlanta, GA, USA; 7 Brown Univ, Providence, RI, USA; 8 Univ Coll London, London, UK Background: Antiretroviral therapy (ART) is pivotal for controlling HIV-1 infection through widescale treatment as prevention (TasP) and pre exposure prophylaxis (PreP). Tenofovir (TDF) is a key component of both approaches, though few data exist on regional burden of TDF resistance and the risk factors for its emergence. hylaxis (PreP). Tenofovir (TDF) is a key component of both approaches, though few data exist on regional burden of TDF resistance and the risk factors for its emergence. Methods: We conducted an international multi-centre retrospective study of individuals undergoing genotyping following virological failure with 1 st -line TDF-containing ART (with a 3TC or FTC plus either efavirenz (EFV) or nevirapine (NVP)). Meta-analysis and multiple logistic regression were used to identify covariates associated with emergence of TDF resistance (defined as presence of K65R/N or K70E/G/Q mutations). Results: Prevalence of TDF resistance amongst 1926 patients in 36 countries with treatment failure (as locally defined) was highest in low and middle income regions: 59.8% West/Central, 55.9% in Eastern and 55.2% in Southern Africa; 39% in Asia; 35.3% in Latin America, and lowest in high income regions: 18.8% in Western Europe and 22.6% in North America. Pre-ART CD4 cell count was associated with TDF resistance across regions (OR 1.49 (1.26-1.77) for CD4 count <100 cells/mm 3 versus ≥100 cells/mm 3 ). Use of 3TC versus FTC and NVP versus EFV increased the risk of tenofovir resistance [OR 1.49 (1.20 – 1.84)] and [OR 1.46 (1.28-1.67)] respectively across regions. The mean plasma viral load at virological failure was not different in the presence or absence of TDF associated mutations [145,700 copies/ml (SE 12,480) versus 133, 900 copies/ml (SE 16650), p=0.626]. Conclusions: TDF resistance emerges in a high proportion of patients who develop virological failure on a TDF-containing first line regimen in low-middle income regions. The risk of TDF resistance was also independently associated with a pre-ART CD4 count <100, the use of 3TC compared with FTC, and the use of EFV compared with NVP. Based on viral loads at faliure, TDF-resistant viruses have the potential to be as transmissible as viruses without TDF resistance. 504 Incompatibility of HIV-1 Resistance to Both Cenicriviroc and Neutralizing Antibodies Takeo Kuwata 1 ; Ikumi Enomoto 1 ; Masanori Baba 2 ; Shuzo Matsushita 1 1 Kumamoto Univ, Kumamoto, Japan; 2 Kagoshima Univ, Kagoshima, Japan Background: Cenicriviroc is a CCR5 antagonist, which prevents human immunodeficiency virus type 1 (HIV-1) from cellular entry. The CCR5-binding regions of the HIV-1 envelope glycoprotein are important targets for neutralizing antibodies (NAb), and cenicriviroc-resistant mutations may therefore affect sensitivity to NAbs. Methods: We used in vitro induction of HIV-1 variants resistant to cenicriviroc or NAbs. Sensitivity of resistant variants and their recombinants to cenicriviroc and to NAb was determined to examine the relationship between resistances to cenicriviroc and to NAb. Results: The cenicriviroc-resistant variant KK652-67, which was isolated in vitro in the presence of an increasing concentration of cenicriviroc, was sensitive to neutralization by NAbs against the V3 loop, the CD4-induced (CD4i) region, and the CD4-binding site (CD4bs), compared with the parental HIV-1 strain KKWT fromwhich cenicriviroc-resistant KK652-67 was obtained. The V3 region of KK652-67 was important for cenicriviroc resistance, similar to other CCR5 antagonists, and critical to the high sensitivity of NAbs to the V3, CD4i, and CD4bs epitopes. Moreover, variants resistant to anti-V3 NAb 0.5γ and anti-CD4i NAb 4E9C were induced from cenicriviroc-resistant KK652-67 by in vitro passages in the presence of each NAb. Acquisition of resistance to both 0.5γ and 4E9C resulted in reversion to the cenicriviroc-sensitive phenotype comparable to the parental KKWT. Resistance to 0.5γ and 4E9C was caused by novel mutations, R315K, G324R, and E381K, in the V3 and C3 regions near the cenicriviroc-resistant mutations. Importantly, these amino acid changes in the CCR5-binding region were also responsible for reversion to the cenicriviroc-sensitive phenotype. Conclusions: These results suggest the presence of key amino acid residues where resistance to cenicriviroc is incompatible with resistance to NAbs. This implies that cenicriviroc and neutralizing antibodies may restrict the emergence of resistant variants each other.

Poster Abstracts

195

CROI 2016