CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

150LB LINKAGE TO CARE AFTER HIV SELF-TESTING IN ZIMBABWE: A CLUSTER- RANDOMISED TRIAL Euphemia Sibanda 1 , Melissa Neuman 2 , Mary Tumushime 1 , Karin Hatzold 3 , Constancia Watadzaushe 1 , Miriam N. Mutseta 4 , Jeffrey Dirawo 1 , Sue Napierala 5 , Getrude Ncube 6 , Miriam Taegtmeyer 7 , Cheryl Johnson 8 , Katherine Fielding 2 , Helen A. Weiss 2 , Elizabeth L. Corbett 2 , Frances Cowan 7 1 Centre for Sexual Health and HIV/AIDS Research Zimbabwe, Harare, Zimbabwe, 2 London School of Hygiene & Tropical Medicine, London, UK, 3 Population Services International, Washington, DC, USA, 4 Population Services International, Harare, Zimbabwe, 5 RTI International, San Francisco, CA, USA, 6 Ministry of Health and Child Welfare, Harare, Zimbabwe, 7 Liverpool School of Tropical Medicine, Liverpool, UK, 8 WHO, Geneva, Switzerland Background: HIV self-testing (HIVST) enables novel strategies, but needs new approaches to maximise linkage to care. We investigated: 1) whether financial incentives for community-selected volunteers (CVs) who distributed HIVST-kits improved timely linkage, and 2) if community-based HIVST increased facility- based ART initiation. Methods: Trained CVs distributed HIVST kits door-to-door for 4-6 weeks in 38 rural wards in Zimbabwe. Using a cluster-randomised design with 1:1 randomisation of wards, CVs were allocated to receive stipend-only (one-off payment of US$50) or stipend-plus: US$50 + US$0.20 incentive per client linked to confirmatory HIV testing, non-communicable disease screen, family planning or male circumcision. Client self-report of HIVST uptake and linkage was assessed 6 weeks later by population survey. The primary outcome was linkage to any post-HIVST service, analysed with random-effects logistic regression, adjusted for imbalance between arms. We used a difference-in-differences quasi-experiment to investigate trends in ART initiation at public facilities in both HIVST and non-HIVST communities, from 6 months before to 3 months after HIVST distribution. Generalised estimation equations (GEE) were used to analyse the relationship between campaign period and trial arm on ART initiation. . Results: A total of 39,205 HIVST kits were distributed by 445 CVs in the stipend-plus arm (mean/CV 88; 95%CI 85-92) and 41,173 by 447 CVs in the stipend-only arm (mean/CV 93; 95%CI 89-96). Overall 7,146/ 8,566 (83.4%) household members responded at 6 weeks; 50.3% had self-tested, 46.5% in males and 46.2% in young people <25 years old. Self-test HIV prevalence was 8.0%; 36.3% of self-testers were first-time testers. Incentives had no effect on the primary outcome, but confirmatory testing by newly diagnosed/untreated HIVST+ clients was significantly higher in the stipend-plus arm, 25/33 (75.8%) versus 20/40 (50.0%), adjusted risk ratio 1.59, 95%CI 1.05-2.39 (Table). GEE modelling of 12,808 ART initiations from 168 clinics (1192 clinic-months) showed a 27% increase in ART initiation in HIVST versus non-HIVST communities (95%CI 14-43%), with no difference by incentive arm (Table). Conclusion: Community-based HIVST campaigns achieved high uptake, including among youth, men and first-time testers, and increased demand for ART. A small linkage incentive to distributors may have increased timely linkage to care in HIV-positive participants not already on ART. Funding: UNITAID-PSI STAR, PACTR20160700170178

Background: HIV-1 establishes latency in resting memory CD4+ T cells, creating a major barrier to eradication. Assessing the efficacy of HIV-1 cure strategies is hindered by the lack of an accurate and scalable assay for latent HIV-1. Standard DNA PCR assays overestimate the latent reservoir by 10-100 fold and mainly measure defective proviruses. The quantitative viral outgrowth assay (QVOA) does not capture all proviruses with potential to cause rebound. To address these issues, we developed an entirely novel approach to reservoir measurement that is rapid and scalable. Methods: Defective proviruses make up over 93% of all proviruses; the most common defects are large internal genome deletions and APOBEC-mediated G to A hypermutation. We analyzed 338 sequences containing large deletions obtained via full-genome sequencing from 28 ART-suppressed individuals. Our analysis indicated that simultaneously probing the HIV-1 genome with two selected amplicons correctly identifies 90% of deleted proviruses as defective. To address hypermutation, we incorporated a pair of probes in one amplicon that distinguish between hypermutated and intact proviruses. Employing both of these features using droplet digital PCR (ddPCR) to analyze proviruses on an individual level, we developed an intact proviral DNA assay (IPDA) which eliminates 95% of all defective proviruses and is predicted to overestimate the reservoir by only 1.9 fold. Results: Extensive plasmid controls and HIV-1 cell lines validated the specificity and linearity of the IPDA. We assessed the reservoir size in 29 HIV-1 infected, ART suppressed individuals using the IPDA and compared to QVOA and total DNA measurements. The median frequency of cells with intact proviruses (IPDA) was 56.23 per million CD4+ T cells. The frequencies measured by the IPDA were a median of 52-fold higher than those measured by QVOA and 19-fold lower than total DNA measurements. For 13 of the HIV-1 infected individuals, we assessed the correlation between the fraction of intact proviruses as measured by IPDA and by full-length, single genome sequencing and found a significant correlation. Conclusion: The IPDA correctly distinguishes intact proviruses frommost deleted or hypermutated proviruses by interrogating the HIV-1 genome in regions commonly deleted or mutated by APOBEC3G. By measuring primarily intact proviruses, we anticipate the IPDA will better assess the impact of eradication strategies on the true reservoir of virus that must be eliminated to achieve an HIV-1 cure. 152LB CLONES OF CD4 T CELLS WITH UNIQUE GENE SIGNATURE CONTRIBUTE TO HIV-1 PERSISTENCE Lillian B. Cohn 1 , Israel T. da Silva 2 , Renan Valieris 2 , Amy Huang 1 , Julio C. Lorenzi 1 , Yehuda Z. Cohen 1 , Joy A. Pai 1 , Allison Butler 1 , Marina Caskey 1 , Mila Jankovic 1 , Michel Nussenzweig 1 1 The Rockefeller University, New York, NY, USA, 2 AC Camargo Cancer Center, São Paulo, Brazil Background: Latently infected CD4+ T cells are the major barrier to HIV-1 cure. These cells have been difficult to study due to their scarcity in blood and lack of distinguishing surface markers. To investigate the cells that contribute to the latent reservoir, we developed a method to enrich and isolate reactivated latent cells from ART suppressed donors by combining antibody staining, magnetic enrichment, and flow cytometry (latent cell capture, or LURE). Methods: Surface expression of viral Envelope protein was used to enrich reactivated latent T cells producing HIV-RNA by combining antibody staining, magnetic enrichment, and flow cytometry. Single cell RNA sequencing was performed to obtain a more comprehensive understanding of the nature of the captured reactivated primary latent cells. Results: We obtain enrichment of reactivated latent T cells producing HIV-RNA. The degree of enrichment was found to be dependent in part on the size of the latent reservoir as measured by viral outgrowth assays in infectious units per million. We performed virus reconstruction from single cell RNA sequencing reads to identify intact, full length virus produced by single cells. Viruses reconstructed from single cells were identical to those found in viral outgrowth cultures. These captured cells represent clones of in vivo expanded T cells as determined by the sequence of their T cell receptors. Comparison of gene expression data from reactivated latent cells to autologous activated uninfected cells or to productively in vitro infected cells revealed a specific gene signature that prominently includes genes implicated in silencing the virus. Conclusion: We conclude that reactivated latent T cells share a gene expression program that may allow for cell division without activation of the cell death pathways that are normally triggered by HIV-1 replication. We speculate

Oral Abstracts

151 NOVEL PARADIGM FOR MEASURING HIV-1 RESERVOIR ALLOWS QUANTITATION OF INTACT PROVIRUSES

Katherine Bruner 1 , Alexandra J. Murray 1 , Ya-Chi Ho 2 , Gregory Laird 1 , Zheng Wang 1 , Kyungyoon J. Kwon 1 , Subul A. Beg 1 , Andrew Timmons 1 , Sarah B. Laskey 1 , Janice E. Clements 1 , Janet Siliciano 1 , Robert Siliciano 1 1 Johns Hopkins University, Baltimore, MD, USA, 2 Yale University, New Haven, CT, USA

55

CROI 2018