CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Background: Estimating HIV and Hepatitis C virus (HCV) incidence from cross-sectional data is critically important to monitor epidemics, and plan and evaluate intervention programs. To date, incidence estimation has focused on HIV using multiassay algorithms (MAA), pooled RNA testing, or age based prevalence models. Leveraging estimated infection duration as a proxy for time- at-risk, a method proposed by Osmond et. al. (1994) for use in populations of young men who have sex with men, we estimate HIV and HCV incidence among persons who inject drugs (PWID) in India. Methods: 14,450 PWID were recruited from 15 Indian cites using respondent driven sampling. Using Osmond’s approach, annual HIV incidence was estimated as the ratio of the number of individuals seropositive divided by person-years (PY) at risk, which was time since injection initiation for those HIV- or HIV+ without a prior positive test. For HIV+ individuals with a prior positive test, PY at risk was estimated as the time between injection initiation and last test date. Modifications were made by reducing PY by predetermined fractions (1/2, 1/3, 1/4) among those who HIV+ without a prior positive test to account for the likelihood of seroconversion earlier in an individual’s injection history. Estimated HIV incidence from the Osmond approach was compared to estimates from a validated MAA. We also used the Osmond approach to estimate HCV incidence. Results: Annual HIV incidence using the Osmond approach was 2.4% (95% CI: 2.3-2.5) compared to 2.5% (CI: 2.0-2.9) using the MAA (Figure 1). Annual HIV incidence estimates increased to 2.6%, (CI: 2.5-2.7), 2.7% (CI: 2.6-2.8), and 2.7% (CI: 2.6-2.8), when truncating PY by 1/2, 1/3, and 1/4 respectively. Osmond annual HIV incidence by site ranged from 0.7% in Bhubaneshwar to 6.8% in Moreh. The Osmond approach tended to overestimate the MAA in sites where fewer PWID reported prior HIV testing. Osmond annual HCV incidence was 4.8% (CI: 4.7-4.9), and increased to 6.1%, (CI: 6.0-6.3), 6.7% (CI: 6.5-6.9), and 7.1% (CI: 6.9-7.2), when truncating the PY of HCV+ individuals without a prior positive HCV test by 1/2, 1/3, and 1/4, respectively. Osmond annual HCV incidence by site ranged from 0.4% in Gangtok to 9.7% in Kanpur. Conclusion: These findings suggest HIV incidence among PWID can be estimated from cross-sectional data using a simpler and less laboratory intensive approach. HCV incidence was higher than HIV incidence, and was more variable because prior HCV testing in this population was low (8.7%).

activation state of LCs changes susceptibility to HIV-1, leading to LC infection and subsequent HIV-1 transmission. In this study we investigated the role of LCs in HCV infection and transmission. We hypothesized that HIV-1 replication in HIV-1-infected MSM leads to mucosal changes that allow HCV entry and subsequent dissemination to hepatocytes. Methods: Therefore, we analyzed the immune cells within mucosal anal biopsies from HIV-1 infected MSM individuals as a potential entry route for HCV during sexual contact. We investigated the role of LCs in HCV infection and transmission using human primary isolated LCs and the ex vivo tissue transmission model. Results: Notably, we detected Langerhans cells (LCs) within the mucosal anal tissue. Immature LCs were neither infected nor transmitted HCV to hepatocytes in vitro and ex vivo. As sexual transmission is mostly observed within HIV-1 infected individuals, we pre-exposed tissues with HIV-1 and, strikingly, HIV-1 pre-exposure significantly increased HCV transmission by LCs. HIV-1 replication is crucial for the increased HCV transmission as treating ex vivo tissue with HIV-1 replication inhibitors significantly decreased HIV-1-induced HCV transmission. Activation of LCs did not lead to infection by HCV but these activated LCs, in contrast to immature LCs from same donor, were efficient in transmitting HCV to hepatocytes. Conclusion: Thus, our data strongly suggest that HIV-1 replication in mucosal tissues in HIV-1 infected MSM changes LC function, which causes HCV capture and subsequent transmission to hepatocytes. This novel transmission mechanism by LCs implicates also that the activation state of LCs is an important determinant for HCV susceptibility after sexual contact. 589 CHANGE IN HIV RISK BEHAVIOR IN PWID ON HCV TREATMENT WITH OR WITHOUT OAT AND PrEP Sarah Kattakuzhy 1 , Laura Nussdorf 2 , Kristi Hill 2 , Rachel Silk 1 , Chloe Gross 1 , Elizabeth Akoth 1 , PoonamMathur 1 , Benjamin Emmanuel 1 , Nadeera Sidique 3 , Chloe S. Chaudhury 2 , David Sternberg 4 , Henry Masur 2 , Shyam Kottilil 1 , Elana S. Rosenthal 1 1 University of Maryland, Baltimore, MD, USA, 2 NIH, Bethesda, MD, USA, 3 Drexel College of Medicine, Philadelphia, PA, USA, 4 University of Maryland, College Park, College Park, MD, USA Background: People who inject drugs (PWID) have a significantly increased risk for HIV infection. In this regard, HCV infection may foreshadow HIV acquisition in current epidemics. Studies of PWID have demonstrated a high desire to obtain HCV treatment, therefore, offering HCV treatment may provide an opportunity to engage PWID in services to prevent HIV transmission, such as buprenorphine and pre-exposure prophylaxis (PrEP). The ANCHOR study was developed to investigate a model of comprehensive care to treat HCV and reduce harm in PWID. Methods: The ANCHOR study is an ongoing single center study evaluating treatment of HCV embedded in an urban harm reduction center. Enrolled patients have chronic HCV, opioid use disorder, and injected opioids within 3 months. Patients are treated with sofosbuvir/velpatasvir and offered uptake of buprenorphine and PrEP. The Darke HIV Risk Taking Behaviour Survey (HRBS) is administered at day 0, weeks 4, 12, 24, 48, 72, and 96. Paired t-test analysis was performed to evaluate for statistically significant changes in HIV risk behavior from day 0 to week 4. Results: 55 HIV seronegative patients are enrolled and started on sofosbuvir/ velpatasvir. Participants are predominantly male (76%), median 57 years, black race (96%). Week 4 data is available on 44 (80%) participants. Of those, 16 (29%) were on opioid agonist therapy (OAT) at screening and 22 (50%) started buprenorphine by week 4. No patients were on PrEP at baseline, and 11 (20%) started PrEP by week 4. There was an overall significant mean decrease in HRBS score in all patients (-2.3, P=0.0028) and among patients who started both PrEP and buprenorphine (-5.1, P=0.007). In patients who started buprenorphine alone, a significant decrease in HRBS drug risk sub-score was found (mean -2.4, p=0.03), however not in the overall score. There was no significant HRBS change based on baseline OAT status or PrEP uptake alone. At the time of CROI, results will be available for 100 patients. Conclusion: Preliminary results at week 4 of the ANCHOR study support that initiation of HCV treatment is associated with decreased HIV risk taking behaviors in PWID with HCV. Collocating buprenorphine and PrEP with HCV therapy in PWID may provide an opportunity to further ameliorate the risk of HIV acquisition. However, long term outcome data are needed to assess if this effect is amplified over the course of treatment, and sustained beyond SVR.

Poster Abstracts

588 HIV-1 ENHANCES SEXUAL TRANSMISSION OF HEPATITIS C VIRUS BY HUMAN LANGERHANS CELLS Bernadien Nijmeijer , Ramin Sarrami Forooshani, Gaby Steba, Richard Molenkamp, Renee Schreurs, Matthijs Siegenbeek van Heukelom, Marc van der Valk, Carla Ribeiro, Teunis Geijtenbeek Academic Medical Center, Amsterdam, Netherlands Background: Sexual transmission of Hepatitis C virus (HCV), until recently, was thought to be rare. However, there has been a significant rise in the incidence of HCV infection among HIV-infected men-who-have-sex-with-men (MSM) and studies suggest that HCV can be sexually transmitted within this population. The mechanisms underlying this sexual transmission are unclear. Human Langerhans cells (LCs) have been shown to be involved in limiting dissemination upon sexual contact by degrading HIV-1 and preventing HIV-1 transmission. The

CROI 2018 216