CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

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 delivery was associated with higher pre-ART VL (relative odds [RO] 0.39 for a 1-log increase in pre-ART VL, p<0.001); later GA at ART initiation (RO, 0.87 for a 1-week increase in GA at ART initiation, p<0.001); and inversely associated with higher pre-ART CD4 cell counts (RO, 1.08 for a 50-unit increase in pre-ART CD4 cell count, p=0.025).

Oral Abstracts

Conclusions: These data provide novel evidence on VS after ART initiation in pregnancy in African populations using a standardised first-line regimen. The rapid early declines in VL to <3 log within a month on ART in most women are encouraging. However one-quarter of the cohort still had detectable VL at the time of delivery, demonstrating the importance of early initiation of ART in pregnancy.

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CROI 2015