CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Conclusion: We did not see a difference in treatment response between NS patients treated with PenG or APPG. Although treatment was not randomized, we continued to see no difference in response even after taking into account pre-treatment differences. 751 STOPPING SECONDARY TE PROPHYLAXIS IN SUPPRESSED PATIENTS WITH CD4 100-200 IS NOT SAFE Jose MMiro , for the Opportunistic InfectionTeam of the COHERE in EuroCoord IDIBAPS, Barcelona, Spain Background: Current guidelines recommend that secondary Toxoplasma gondii prophylaxis can be safely discontinued in HIV-infected patients with suppressed viremia on antiretroviral therapy (ART) and a CD4 cell count >200 cells/mm3. Whether such a policy can be extended to patients with CD4 cell counts between 100-200 cells/mm3 is unknown. Methods: The Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) included data from 10 European cohorts on 1151 HIV-infected patients who developed a toxoplasmic encephalitis (TE) and started ART after 1997. TE was diagnosed on the basis of the 1993 CDC case definition. A relapse was defined as a new TE episode after 4 months of the initial TE. Patient follow-up began at the date of the first TE and ended at the time of first TE relapse, last visit, or death, whichever occurred first. Incidence rates of TE relapses were calculated after stratification by current use of prophylaxis, current CD4 cell count, and current viral load (VL). Multivariate Poisson regression models were used to model incidence rate ratios (IRRs) of TE. Results: There were 79 TE relapses during 6,030 person-years of follow-up (PYFU). The incidence of TE relapses stratified by current CD4 cell count, detectable or undetectable VL, and use of prophylaxis is shown in the figure. Among patients who had a current CD4 cell count of 100-200 cells/mm3 and an undetectable VL (<400 copies/mL), incidence of TE was 0.9 episodes per 100 PYFU (95% CI, 0.11-3.2; 2 episodes during 224 PYFU) in those receiving T. gondii prophylaxis and 1.9 relapses per 100 PYFU (95% CI, 0.75-3.8; 7 episodes during 376 PYFU), in those who stopped prophylaxis (P=0.349). Among virologically suppressed patients on ART without secondary T. gondii prophylaxis, the incidence of TE in patients with CD4 100-200 was significantly higher than that seen in patients with CD4>200 cells/mm3 (0.5 (95% CI, 0.3-0.8) episodes per 100 PYFU; P=0.002). Doubling CD4 cell count/mm3 (IRR, 0.77; 95% CI, 0.68–0.87; P<.001) was the only TE relapse predictor; whereas detectable VL (IRR, 1.64; 95% CI, 0.92–2.93; P=0.092) and prophylaxis (IRR, 1.00; 95% CI, 0.61–1.64; P=.998) were not predictors. Conclusion: In suppressed HIV-infected adult patients, secondary prophylaxis against TE can be safely discontinued in patients with CD4 cell counts >200 cells/mm3. Conversely, secondary TE prophylaxis should not be stopped in virologically suppressed patients with CD4 counts of 100-200 cells/mm3

Poster and Themed Discussion Abstracts

752 ASYMTOMATIC INFECTION IN AN HIV COHORT: LEISHMANIASIS OUTBREAK IN FUENLABRADA, SPAIN Alicia Castro 1 , Eugenia Carrillo 2 , Juan V. San Martin 1 , Laura Botana 2 , Laura Molina 1 , Laura Fernandez 2 , Belen Matia 1 , Carmen Sanchez 2 , Jose Manuel Ruiz-Giardin 1 , Javier Moreno 2 1 Hosp Univ de Fuenlabrada, Fuenlabrada, Madrid, Spain, 2 Inst de Salud Carlos III, Majadahonda, Spain Background: The largest leishmaniasis outbreak in Europe was declared since June 2009 in Fuenlabrada (Madrid, Spain). Our aimwas to estimate the prevalence of asymptomatic Leishmania infection in the HIV cohort of Fuenlabrada, in this high exposure setting, and analyze the risk factors for the development of visceral leishmaniasis. Methods: A representative sample of the Fuenlabrada’s HIV cohort was selected for exposure test to Leishmania. An infected patient was defined as a positive result in, at least, one of following blood tests for Leishmania: PCR, serology (ELISA or IFAT) or SLA (stimulation to Leishmania antigen) lymphoproliferative test as marker of cellular immunity. Infected vs not infected patients, and visceral leishmaniasis vs asymptomatic infected patients, were analyzed with statistical tests looking for risk factors. This work has been supported by “Red de Investigación Cooperativa en Enfermedades Tropicales” (RICET + RD12/0018/0008), VI PN de I + D + I 2008–2011, ISCIII- Subdirección General de Redes y Centros de Investigación Cooperativa; and fondos FEDER Results: 583 patients of the Fuenlabrada’s HIV cohort were followed since 1st June 2004 to 31th December 2015. 135 representative patients were selected for exposure test to Leishmania, including 12 symptomatic patients (10 visceral and 2 cutaneous). 19 (15.4%) of the 123 asymptomatic patients fulfilled the definition for Leishmania infection, none of them became symptomatic during the study period. Total prevalence of the cohort was estimated 17.5%. Multivariate analysis was performed in infected vs not infected patients and find association to the “distance to Bosquesur park”, considered the focus of the outbreak, 1082 meters media distance to the park in infected vs 1719 meters not infected (ANOVA p=0.02). Multivariate analysis performed between patients who developed visceral leishmaniasis vs asymptomatic patients showed association to illness development only for patients with “negative SLA test with positive PCR or serology” (p<0,001, OR not calculable) and “less than 100 CD4 during outbreak period” (p=0,001, OR not calculable). Conclusion: In the TARGA era, 15.4% of our HIV cohort has been infected by Leishmania, but are asymptomatic. Negative SLA test with positive PCR or serology, reflects the absence of specific immune response to Leishmania, and is therefore an independent risk factor for visceral leishmaniasis 753 DOSING FOR TWO: PLACENTAL TRANSFER OF DARUNAVIR AND SIMULATION OF FETAL EXPOSURE Stein Schalkwijk , Aaron O. Buaben, Angela Colbers, David M. Burger, Rick Greupink, Frans G. Russel Radboud Univ Med Cntr, Nijmegen, Netherlands Background: Fetal antiretroviral exposure is usually derived from the cord-to-maternal (ctm) concentration ratio. This static parameter does not provide information on the pharmacokinetics in utero, limiting the assessment of a fetal exposure-effect relationship. Pregnancy physiologically-based pharmacokinetic (p-PBPK) modeling could provide a solution, although incorporation of placental antiretroviral transfer remains challenging. Here, we aimed to incorporate placental transfer into a p-PBPK model to simulate fetal exposure of darunavir at term.

CROI 2017 326