CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

374 Decay Rate and HIV-1 DNA Reservoir Size Following Early Infant Antiretroviral Therapy Priyanka Uprety 1 ; Kaitlin Rainwater-Lovett 2 ; Ellen G. Chadwick 3 ; Edmund Capparelli 4 ; Carrie Ziemniak 2 ; Katherine Luzuriaga 5 ; Larry Moulton 1 ; Deborah Persaud 2 International Maternal Pediatric Adolescent AIDS ClinicalTrial Network (IMPAACT) P1030 trial group 1 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 2 Johns Hopkins University School of Medicine, Baltimore, MD, US; 3 Northwestern University, Feinberg School of Medicine, Chicago, IL, US; 4 University of California San Diego, San Diego, CA, US; 5 University of Massachusetts Medical School, Boston, MA, US Background: In a perinatally HIV-infected child, ART at 30 hours of life was associated with reduced human immunodeficiency virus (HIV) reservoirs and 27 months of virologic remission. Knowledge of infected cell frequencies and decay as a function of age at ART is important for informing clinical trials aimed to study these effects. Methods: 18 perinatally HIV infected infants in a multicenter, open-label, phase I/II, trial of lopinavir+ritonavir-based ART (IMPAACT P1030 trial) initiated before (early-treated [ET]) or after (late-treated [LT]) 6 weeks (wks) of age were studied. Infants with available samples (n=18) were included in the study if they either achieved a 2-log viral load (VL) decrease from baseline and sustained VL<400 by 48 weeks or achieved and maintained VL to <400 by 24 weeks.Total PBMC HIV DNA and 2-LTR circles were quantifed by droplet digital PCR (<3 copies/million (c/m) at baseline, 24, 48, and 96 wks of ART and linear decay rates were estimated for each infant. Total HIV DNA was correlated with age at ART, and HIV DNA levels during ART. All data are reported as mean and 95% confidence interval, except for age of ART which is reported as median and range. Results: The median age of ART initiation was 5.71 (4.30-5.86) and 11.14 (6.86-23.43) wks for ET (n=5) and LT (n=13) infants, respectively. Before ART, HIV DNA in ET and LT was 3.16 [2.53, 3.78] and 3.27 [2.80,3.73] log 10 copies/million (c/m) (p=1.00). Overall, HIV DNA decayed faster in ET vs. LT (-0.034 [-0.054,-0.015] vs. (-0.017 [-0.022, -0.013] log 10 c per wk; p=0.03). From 0 to 24 wks of ART, HIV DNA decreased by 1.25 [0.96,1.55] and 0.89 [0.75,1.02] log 10 c/m in ET and LT, respectively (p=0.008), but did not differ between groups from 24 to 48 wks (p=0.58). After 48 weeks of ART, there was a trend towards lower HIV DNA in ET vs. LT (1.26 [-0.19,2.71] vs. 2.11 [1.51, 2.71] log 10 c/m; p=0.08). Overall, HIV DNA load at baseline was highly correlated with HIV DNA load at 24, 48 and 96 wks of ART (p<0.001). 2-LTR circles were detectable at baseline in 80% and 77% (p=1.00), at 24 weeks in 25% and 83.4% (p=0.12) and at 48 weeks in 0% and 80% (p=0.03) of ET and LT infants, respectively. Conclusions: Earlier initiation of ART did not substantially affect pre-ART infected cell frequencies but was associated with faster HIV decay. However, HIV-1 DNA burden established before initiation of ART determined the DNA reservoir during suppressive ART. 375 Detectable CMV in PBMC Is AssociatedWith Slower HIV DNA Decay During Suppressive ART Sara GianellaWeibel ; Christy Anderson; Susanna R.Var; Michelli Faria de Oliveira; Marta Massanella; Susan J. Little; Douglas D. Richman; Matt Strain; Josue Pérez-Santiago; David M. Smith University of California San Diego, La Jolla, CA, US Background: Asymptomatic CMV replication is frequent in HIV infected men, and is associated with increased immune activation, T cell proliferation and HIV disease progression. We hypothesized that persistent CMV replication influenced HIV DNA dynamics after initiation of antiretroviral therapy (ART) during early HIV infection. Methods: We investigated 397 peripheral blood mononuclear cell (PBMC) samples collected from 96 CMV-seropositive, recently HIV-infected men. Participants started ART within a median of 5 months from estimated date of infection (EDI) (range: 0-8), achieved suppressed HIV RNA in blood within a median of 6 months on ART (range: 1-8) and were followed for a median of 17 months after ART start (range: 12-75). The median CD4 count at presentation was 485 cells/ m l and the median peak HIV RNA was 4.8 log 10 HIV RNA cp./ml. Levels of CD4-associated HIV DNA and CMV DNA were measured by droplet digital PCR for each time-point (mean 4 TP/participant). Using a general linear mixed-effect regression model, associations between HIV DNA decay, age, frequency of detectable CMV, nadir CD4 count, peak HIV RNA level, time from EDI to ART start, and time from ART start to virologic suppression were evaluated. Results: Higher peak HIV RNA levels and higher frequency of detectable CMV in PBMC (>40% of sampled time-points) were associated with increased levels of HIV DNA during ART (p<0.01). Both factors were independently associated with higher HIV DNA in multivariable analysis (p<0.01). No other variable contributed significantly. The pattern of HIV DNA decay during ART differed significantly between participants with higher versus lower frequency of detectable CMV in PBMC (> vs < 40% of samples with detectable CMV). When considered separately, a linear model had a significantly better fit for HIV DNA decay in the low-frequency CMV group, while a quadratic model of HIV DNA decay had a better fit for participants with higher frequency of CMV DNA (p<0.01, see figure). In other words, individuals with more detectable CMV demonstrated a U-shaped pattern of HIV DNA decay while the low frequency CMV group had a linear pattern of decay.

Poster Abstracts

When considered separately, a linear model had a significantly better fit for HIV DNA decay in the low-frequency CMV group (<40% detectable CMV, left panel), while a quadratic model of HIV DNA decay had a better fit for participants with higher frequency of CMV DNA (>40% detectable CMV, right panel). Conclusions: Detectable CMV DNA in PBMC is associated longitudinally with higher HIV DNA levels, even among individuals who started ART early during HIV infection, suggesting that CMV replication may help maintain the stability of the HIV DNA reservoir. Future studies with anti-CMV therapeutics could help determine underlying mechanisms and if causal associations exist.

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CROI 2015