CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Methods: We previously estimated vaginal SHIVSF162P3 acquisition time points after repeated virus exposure throughout the menstrual cycles of 43 pigtail macaques (Macaca nemestrina). Cycles of 16 different macaques were monitored for 80 days to determine days 1-16 and 17 and up (follicular and luteal phases, respectively). Vaginal biopsies were collected in the two phases. The superficial, non-nucleated (Stratum corneum) and underlying nucleated cell layers were quantitated by microscopy supported by image analysis software. Results: The vaginal epitheliumwas thicker in the follicular than the luteal phase (mean 350, 230 micrometers [um] respectively; p=0.006, Mann-Whitney test). To get a more dynamic picture of thinning, we analyzed four-day segments of the cycle and found the epitheliumwas thickest on days 13-16 (mean 389 um), and thinnest on days 29-32 (134 um). A large relative thickness change occurred in the S. corneumwith a mean 106 and 16 um at these times, respectively. The number of animals with estimated SHIV acquisition in each four-day menstrual cycle segment strongly correlated with thinness of the S. corneum (Pearson’s r = 0.7, p<0.05), but only moderated correlated with the nucleated cell layer (Pearson’s r=0.5, p=0.17). Conclusions: These data provide a more detailed, dynamic picture of the layered vaginal epithelium during progesterone changes than previously described. Extensive relative thinning occurred in the superficial S. corneum. This glycogen-rich layer has terminally differentiated cells, likely maintains the vaginal microbiome and exfoliates invading pathogens. Although the relationship with infection data could only be studied using aggregate data from animals in a separate study, the data support S. corneum thinning as a factor in susceptibility to SHIV infection. A better understanding of innate resistance mechanisms to vaginal SHIV or HIV infection could lead to novel HIV prevention strategies for women. 2:30 pm– 4:00 pm How Fast? How Often? Achieving Viral Suppression in Pregnant and PostpartumWomen 863 Specific Effects of ZDV, 3TC and LPV/r on HIV-1 RNA Viral Load During Pregnancy Patumrat Sripan 1 ; Sophie Le Coeur 5 ; Lily Ingsrisawang 2 ;Tim R. Cressey 3 ; Jean-MarcTréluyer 6 ; Naïm Bouazza 4 ; Frantz Foissac 4 ; Gonzague Jourdain 3 ; Marc G. Lallemant 3 ; Saïk Urien 7 1 ED420, University of Paris Sud 11, Paris Descartes, Paris, France/PHPT-IRD UMI 174, Chiang Mai, Thailand/Department of Statistics, Faculty of Science, Kasetsart University, Bangkok, Thailand; 2 Department of Statistics, Faculty of Science, Kasetsart University, Bangkok, Thailand; 3 PHPT-IRD UMI 174, Faculty of Associated Medical Sciences, Chiang Mai University/Harvard School of Public Health, Chiang Mai, Thailand; 4 EA 08 Université Paris Descartes, Sorbonne Paris Cité, Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France; 5 Institut d’Etudes Démographiques, Institut de Recherche Pour le Développement (UMR 196 CEPED), Paris, France/Harvard School of Public Health, Boston, MA, USA/Faculty of Associated Medical Science, Chiang Mai University, Chiang Mai, Thailand; 6 EA 08 Université Paris Descartes, Sorbonne Paris Cité, Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Service de Pharmacologie Clinique, AP-HP, Groupe Hospitalier Paris Centre, CIC-0901 Inserm, Cochin-Necker, Paris, France; 7 EA 08 Université Paris Descartes, Sorbonne Paris Cité, Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, CIC-0901 Inserm, Cochin-Necker, Paris, France Background: HIV-infected women commonly receive zidovudine (ZDV) + lamivudine (3TC) + lopinavir/ritonavir (LPV/r) during pregnancy for the prevention of mother-to-child transmission (PMTCT) in Thailand. Our aims were to evaluate the role of 3TC added to ZDV+LPV/r and the specific effect of each drug on maternal HIV-1RNA viral load (VL) reduction for the PMTCT. Methods: A total of 1,655 plasma VL levels from 702 pregnant women enrolled in the PHPT-5 perinatal HIV prevention trial in Thailand (NCT01511237, NCT00409591) were included. ART naïve pregnant women received either (1) ZDV only (plus nevirapine at onset of labor); (2) ZDV+LPV/r; or (3) ZDV+3TC+LPV/r. HIV-1 RNA VL time courses were analysed using non-linear mixed effect modelling and dependent on VL at treatment initiation and duration of treatments. An Emax response model was used to describe the impact of these ARV regimens on VL reduction during pregnancy. A mechanistically-based equation was developed to determine the contribution of each drug assuming ZDV and 3TC have the same target and mechanism of action, and the effect of LPV/r was added as a separate component. Results: Of the 702 women, 278 (40%) received ZDV monotherapy, 146 (20%) ZDV+LPV/r and 278 (40%) ZDV+3TC+LPV/r during pregnancy. The maximum effect of each regimen on HIV-1 RNA VL was significantly different (p<0.02), with 1.67, 3.8 and 4.57 log 10 copies/mL reduction for ZDV alone, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. Time to reach half of maximum effect (T 50 ) was significantly longer with ZDV alone compared with ZDV+3TC+LPV/r (p<0.001). However there was no significant difference between ZDV+LPV/r and ZDV+3TC+LPV/r (p=0.13). The mechanistically-based model estimated that 110 days of ZDV or 3TC were necessary to achieve half of ZDV or 3TC maximum effect on viral load suppression (maximum effect: minus 1.38 and 2.05 log 10 copies/mL, respectively) whereas only 10 days of LPV/r were necessary to achieve half of LPV/r maximum effect (maximum effect: minus 2.32 log 10 copies/mL). Using the mean VL at treatment initiation (4.07 log 10 copies/mL), the model indicated that the addition of 3TC reduced the time to undetectable VL (<50copies/mL) by 3 weeks: 7.3 weeks with ZDV+LPV/r compared with 4.4 weeks for ZDV+3TC+LPV/r assuming a common T 50 for ZDV and 3TC. Conclusions: The addition of 3TC to ZDV+LPV/r during pregnancy reduces time to reach undetectable VL in pregnant women, especially those with a high VL at treatment initiation and subsequent high risk of MTCT. 864 Viral Suppression After Antiretroviral Therapy Initiation in Pregnancy in South Africa Landon Myer 1 ;Tamsin Phillips 1 ; Nei-Yuan Hsiao 2 ; Allison Zerbe 3 ; Jo Ramjith 1 ; Linda-Gail Bekker 1 ; James A. McIntyre 4 ; Elaine J. Abrams 3 1 University of Cape Town, Cape Town, South Africa; 2 National Health Laboratory Services/University of Cape Town, Cape Town, South Africa; 3 ICAP at Columbia University, New York, NY, US; 4 Anova Health Institute, Johannesburg, South Africa Background: HIV viral load (VL) is the principle determinant of mother-to-child transmission (MTCT) risk and rapid lowering of VL is a primary goal of antiretroviral therapy (ART) for prevention of MTCT. However there are few data on the trajectory of viral load (VL) and time to viral suppression <50 copies/mL (VS) following ART initiation in HIV-infected pregnant women. Methods: Consecutive pregnant women initiating ART in Cape Town, South Africa were recruited into a prospective cohort from ART initiation through delivery, with VL measured immediately prior to initiation (pre-ART), 1-4 weeks after initiation, during the 3rd trimester, and at 1 week postpartum. All women initiated TDF+FTC+EFV. Analyses examined changes in log VL trajectories after initiation using non-linear mixed models, the proportions of women achieving VS over time using product-limit methods, and the probability of VS at delivery using logistic regression. Results: From April 2013 to May 2014, 629 ART-naïve pregnant women were enrolled (median age, 28 years; median CD4 cell count, 343 cells/ m L; median gestation age (GA), 21 weeks; median VL, 4.0 log10 copies/mL [IQR: 3.4-4.6]). Most women achieved VL<3 log within 4 weeks of ART start (Figure 1a) but the median time to VS<50 copies/mL was 14.1 weeks (95% CI, 13.3-15.3). Time to VS was strongly influenced by pre-ART VL: women with VL <3, 3-4, 4-5 and >5 log10 copies/mL before ART initiation had median times to VS of 2.9, 9.6, 17 and 18.9 weeks, respectively (p<0.001; Figure 1b). 75% of women achieved VS by delivery. Adjusting for age and past ARV exposure, decreased probability of VS at TUESDAY, FEBRUARY 24, 2015 Session P-T1 Poster Session Poster Hall

Poster Abstracts

520

CROI 2015