CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

135 ARV PROPHYLAXIS/ART INITIATION AT BIRTH LIMITS THE SIZE OF THE RESERVOIR IN CHILDREN Marta Massanella 1 , Jintanat Ananworanich 2 , Louise Leyre 1 , Thidarat Jupimai 3 , Panadda Sawangsinth 3 , Mark de Souza 4 , Suteeraporn Pinyakorn 2 , Piyarat Suntarattiwong 5 , Pope Kosalaraksa 6 , Thitiporn Borkird 7 , Kulkanya Chokephaibulkit 8 , Suparat Kanjanavanit 9 , Thanyawee Puthanakit 10 , Nicolas Chomont 1 1 Centre de Research du Centre Hospitalier de l’Université de Montreal, Montreal, QC, Canada, 2 US Military HIV Research Program, Bethesda, MD, USA, 3 HIV–NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 4 SEARCH, Bangkok, Thailand, 5 Queen Sirikit National Institute of Child Health, Bangkok, Thailand, 6 Khon Kaen University, Khon Kaen, Thailand, 7 Hat Yai Hospital, Songkhla, Thailand, 8 Mahidol University, Bangkok, Thailand, 9 Nakornping Hosp, Chiang Mai, Thailand, 10 Chulalongkorn University, Bangkok, Thailand Background: Early antiretroviral therapy (ART) limits the size of the HIV reservoir in adults; however pediatric data are limited. We assessed the impact of age of ARV prophylaxis (proARV)/ART initiation on the size of the HIV reservoir in early-treated vertically infected infants. Methods: We measured markers of HIV persistence in infants (4-23 weeks of age) who received uninterrupted triple proARV since birth (n=9) and those who did not receive proARV or interrupted either triple or AZT prophylaxis (n=17). In addition, samples from suppressed children (median 2.7 years of age) who initiated continuous ART/proARV at birth (n=12) or later (range 3-26 weeks, n=63) were also studied. Total and integrated HIV DNA in CD4 T-cells were quantified by real-time PCR and we used TILDA to measure the frequency of CD4 T cells producing multiply spliced RNA (msRNA) as a proxy for virus production, with and without stimulation. Results: Viral loads were significantly lower in infants who received continuous proARV from birth compared to those who interrupted or never received prophylactic treatment (p<0.001). Similarly, levels of integrated HIV DNA tended to be lower in infants receiving uninterrupted proARV compared to those in whom proARV was interrupted or not initiated (p=0.08). The frequencies of cells producing msRNA spontaneously and after stimulation were significantly lower in infants who received uninterrupted proARV (p=0.003 and p=0.005, respectively). Importantly, the frequency of latently infected cells was significantly lower in infants who received uninterrupted proARV since birth (p=0.048). After ART initiation, children who received proARV/ART since birth had significantly lower total and integrated HIV DNA than children starting treatment later (p=0.01 and p=0.03, respectively). Although TILDA values were equally low and often below the limit of detection in both treated groups (43% and 47% samples with detectable TILDA, in the immediate and deferred groups, respectively), the size of the inducible reservoir correlated with age at which continuous proARV/ART was initiated for the first time (r=0.28, p=0.04). Conclusion: Neonatal proARV without complete viral suppression significantly limits the size of the reservoir. Notably, uninterrupted ART dramatically restricts the pool of cells harboring total and integrated HIV DNA. Importantly, the age at which continuous proARV /ART is initiated for the first time impacts the size of the inducible reservoir. 136 LOW HIV RESERVOIR AT 84 WEEKS IN VERY EARLY TREATED HIV- INFECTED CHILDREN IN BOTSWANA Roger L. Shapiro 1 , Mathias Lichterfeld 2 , Michael D. Hughes 1 , Kara Bennett 3 , Kenneth Maswabi 4 , Gbolahan Ajibola 4 , Pilar Garcia-Broncano 5 , Sikhulile Moyo 4 , Terence Mohammed 4 , Patrick Jean-Philippe 6 , Maureen Sakoi 4 , Oganne Batlang 4 , Shahin Lockman 2 , Joseph Makhema 4 , Daniel R. Kuritzkes 2 1 Harvard University, Boston, MA, USA, 2 Brigham and Women’s Hospital, Boston, MA, USA, 3 Bennett Statistical Consulting, Inc, New York, NY, USA, 4 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 5 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 6 NIH, Rockville, MD, USA Background: Markers of HIV-1 reservoir size and immune responses are poorly described in HIV-infected infants treated very early in life. Methods: The Early Infant Treatment Study (EIT) screens HIV-exposed children in Botswana by Roche TaqMan qualitative DNA PCR, and offers antiretroviral treatment (ART) for HIV-infected infants < 7 days of age. Nevirapine, zidovudine (ZDV), lamivudine (3TC) are provided as initial ART, and changed to lopinavir/ ritonavir, ZDV, 3TC at 2+ weeks. Study visits and HIV RNA testing occur at enrollment, weeks 1, 2, 4, 8, 12, 24, then every 3 months. At least 1 million

Johannesburg, South Africa, 7 Malawi Coll of Med–Johns Hopkins Univ Rsr Proj, Blantyre, Malawi, 8 University of Zimbabwe, Harare, Zimbabwe, 9 GHESKIO, Port- au-Prince, Haiti, 10 Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana, 11 Byramjee Jeejeebhoy Government Medical College, Pune, India, 12 National Health Laboratory Service, Johannesburg, South Africa, 13 DAIDS, NIAID, Bethesda, MD, USA, 14 University of Witwatersrand, Johannesburg, South Africa Background: Cytology-based cervical cancer screening, confirmation of high-grade squamous intraepithelial lesions by colposcopic biopsy (bHSIL), and loop electrosurgical excision (LEEP) treatment are difficult to implement in resource-constrained settings. We hypothesized that screening with high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of HPV positive women (HPV Test&Treat) may improve outcomes measured by reduction in bHSIL during follow-up. Methods: A5282 is a randomized, open-label, phase 2, multinational clinical trial enrolling HIV-infected women age 18 or older with cervical hrHPV detected and having no cervical lesions or limited lesions appropriate for cryotherapy. Women were randomized to HPV Test&Treat or Cytology-based screening. For HPV Test&Treat, cervical biopsies were obtained followed by treatment with cervical cryotherapy, and in the Cytology Arm, women with abnormal cytology underwent colposcopy and directed biopsies followed by LEEP if bHSIL was detected. Women were followed every 6 months through 30 months. The primary endpoint was time to bHSIL detected at Month 6 through study completion and compared using log-rank test. The cumulative rate of bHSIL was estimated by the Kaplan-Meier method. Results: HIV+ women (N=288, HPV Test&Treat 145, Cytology-based 143) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm 3 . In the HPV Test&Treat Arm, 39 (27%) of women had bHSIL at entry and 142 (98%) underwent cryotherapy; in the Cytology Arm, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, and LEEP was performed on 12 (8%). In follow-up, time to bHSIL was similar between arms (see Figure, log-rank test p=0.92): 30 (21%) and 31 (22%) developed bHSIL and time to bHSIL was similar between arms (Figure, p=0.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, p=0.13). There were no statistically significant differences in prevalence of abnormal cytology results at any follow-up visit (p≥0.16); bHSIL during study follow-up in the HPV Test&Treat armwere independently predicted by the presence of hrHPV (p=.014) and abnormal cytology (p=.03) at Month 6. Conclusion: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to a single round of cytology-based screening. This may be due to a poorer than expected response to cryotherapy in this population. More effective treatment options are required to improve outcomes from screen-and-treat programs.

Oral Abstracts

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CROI 2018