CROI 2016 Abstract eBook

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Poster Abstracts

Results: Of the 37 children, 14 started cART during the first year of infection (3-12 mo) and 23 children between 20-131 mo. Three time points (pre cART, 2 and 4 years on VS) were able to study in 23 children while in 14 only pre cART and at 4 years on VS could be performed. The median CA-HIV-DNA levels pre cART was 2.67 (IQR: 1.72- 3.07) log 10 /10 6 PBMCs and was significantly lower when compared to 2 and 4 years on VS with median levels of 1.96 (IQR:1.32-2.56) log 10 (p<0.05) and 1.91 (IQR: 0.78-2.36) log 10 /10 6 PBMCs (p<0.005), respectively. However, no changes in CA-HIV-DNA levels between 2 and 4 years on VS was found. Moreover, initiation of therapy before or after 12 months of age did not modify CA-HIV-DNA levels. No correlation between clinical stage or CD4 counts and CA-HIV-DNA levels were found. Conclusions: CA-HIV-DNA levels is markedly reduced by therapy after 2 years of VS. However, once CA-HIV-DNA levels reaches a set point, it remains stable despite prolonged therapy and they could not been reduced by cART initiation between 3 -12 months of age. Collectively, these findings suggest that the strongest effect of cART on viral reservoirs is restricted to a very short period after infection, and extended ART prophylaxis may play a central role to limit the set point of CA-HIV-DNA levels. 838 HIV-1 DNA Dynamics Over a Decade or More of Viral Suppression in Perinatal Infection Priyanka Uprety 1 ; Kunjal Patel 2 ; Brad Karalius 2 ; Kaitlin Rainwater-Lovett 1 ; Carrie Ziemniak 1 ;Ya Chen 1 ; Suzanne Siminski 3 ; Russell B.Van Dyke 4 ; George R. Seage 2 ; Deborah Persaud 1 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Frontier Sci & Tech Rsr Fndn, Inc, Amherst, NY, USA; 4 Tulane Univ Sch of Med, New Orleans, LA, USA Background: In perinatal HIV-1 infection, whether age at and duration of virologic suppression (VS) effects long-term decay of HIV-1-infected cells following ≥10 years of combination antiretroviral therapy (cART) is unknown. Methods: Total HIV-1 DNA was quantified using droplet digital PCR methods in peripheral blood mononuclear cells (PBMCs) from perinatally-HIV-infected youth enrolled in the US-based Pediatric HIV/AIDS Cohort Study who achieved VS (two consecutive plasma viral load [pVL] <400 copies/mL) after cART initiation and maintained suppression during follow-up. Piecewise linear mixed effects regression models estimated HIV-1 DNA trajectories following VS for all study participants (N=61 youths; n=402 PBMC samples during VS), and after stratification into youth with VS before one year of age (Group 1; N=13; n=118), and youth with VS between one and five years of age (Group 2; N=48; n=284). Results: Groups 1 and 2 initiated cART at a median age of 2.1 months and 1.7 years and achieved VS within a median of 5.9 and 10.2 months of cART, respectively. The median duration of VS was 11.9 and 9.5 years for Groups 1 and 2, respectively, with a median of 9 and 5.5 PBMC samples tested per study participant during VS. The median ages at last study visit were 12.6 years for both groups. PVLs and CD4% at cART initiation or at last study visit did not differ between the two groups. Estimated mean HIV-1 DNA concentrations at the time of VS were 2.21 and 2.19 log 10 copies/million PBMCs in Groups 1 and 2, respectively. In the two years following VS, HIV-1 DNA decreased by -0.48 (95% CI: -0.77, -0.18) and -0.15 (95% CI: -0.23, -0.07) log 10 copies/million PBMCs per year in Groups 1 and 2, respectively (Figure). Between two and 14 years after VS, HIV-1 DNA decreased by -0.03 (95% CI: -0.07, -0.00) and -0.05 (95% CI: -0.07, -0.03) log 10 copies/million PBMCs per year, respectively. Following 10 years of VS, estimated HIV-1 DNA concentrations averaged 0.98 and 1.50 log 10 copies/million PBMCs in Groups 1 and 2, respectively. Conclusions: HIV-1 infected cells continually decreased during a decade or more of cART in perinatal infection, irrespective of age at VS. A more rapid decrease in the first two years of VS was observed among those with VS before 1 year of age. The basis of decreasing concentrations of circulating HIV-1-infected cells in perinatal infection requires further study.

Poster Abstracts

839 Value of Ultrasensitive HIV Assay in Infants With Negative Routine Laboratory Results Arjen J. Stam 1 ; Denise van Hout 1 ; Sibyl P. Geelen 1 ; Annelies Riezebos-Brilman 2 ; Joop Schellekens 3 ; E. H. Schölvinck 2 ; KikiTesselaar 1 ;Tom F.Wolfs 1 ; Monique Nijhuis 1 ; Anne M.Wensing 1 1 Univ Med Cntr Utrecht, Utrecht, Netherlands; 2 Univ Med Cntr Groningen, Groningen, Netherlands; 3 CERTE, Groningen, Netherlands Background: Early cART after vertical infection can prevent the development of HIV specific antibodies and has the potential to restrict the size of the HIV reservoir. Ever since the Mississippi baby (who temporarily retained HIV control after early initiated therapy was discontinued) parents question if therapy should be continued in HIV infected children who initiated cART in an early phase after birth and are seronegative. Methods: Case-series of vertically infected children in whom the presence of an ongoing HIV infection was questioned. Clinical data and standard diagnostic data were collected. DNA was extracted from PBMCs or dried blood spots. Detection and quantification of HIV DNA was performed by different ultrasensitive assays (1cp/E6 cells). HIV specific T-cell activity was investigated by ELISPOT Results: 7 children born in Africa who presented at Dutch hospitals after adoption (median age 12 months) were included. At presentation all children had negative HIV serology. Child 1 was treated for 8 weeks with monotherapy and had no written documentation of HIV infection. This infant repeatedly tested negative for HIV-RNA during 21 months off therapy, HIV antibody and ultrasensitive HIV-DNA tests were also negative. All other children had documented records of positive HIV status in the country of origin and had locally initiated cART. HIV RNA could only be detected in infant 2. In this child a slow viral decay was seen before full suppression was reached at 13 months on cART. Despite the prolonged viremia no HIV antibodies or HIV-specific T-cell activity were observed. In child 3 cART was discontinued resulting in a viral rebound (5.64 x 10 6 cp/mL) and HIV seroconversion. Retrospective analysis of PBMC obtained before therapy interruption showed positive HIV DNA results. The four other children continued cART after ultrasensitive DNA assays confirmed the HIV infection. Conclusions: Standard diagnostic tests can provide false hope of a cure and erroneous discontinuation of cART with risk of viral rebound. By using ultrasensitive tools developed to investigate the viral reservoir, HIV infection could be confirmed in children with negative HIV serology and undetectable viral loads. In one child, without any proper documentation of HIV status, the negative ultrasensitive DNA tests reinforced the decision to stop ART and led to the conclusion that it is unlikely this child was infected with HIV. Remarkly no HIV specific T-cell immunity was mounted in one child despite prolonged viremia.

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CROI 2016