CROI 2019 Abstract eBook

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Oral Abstracts

trained and qualified to provide HIV testing and dispense PrEP, the so called “key population-led health services or KPLHS”, to around 50% of all Thai PrEP users. Four years after Thai Guidelines recommended PrEP, only 4% of 150,000 Thais at risk access PrEP. Government needs to de-medicalize PrEP and accept KPLHS roles in ending AIDS now. Over a decade, the world’s largest cohort (RV254) of 600 acute HIV cases has been established at TRC-AC. Through available routine NAT screening, early and frequent HIV testing has formed among certain populations. Immediate ART, together with extensive virologic/immunologic studies, demonstrated very low HIV reservoir even though there is no good news so far for HIV remission/cure. Crucial data for global HIV cure research are generated from Thailand although it is still too far away to get government’s attention. Achievements described is the outcome of continuing commitment of government, civil society, academics and royal family. Policy makers and politicians, who change frequently, are vital in the process since all successful pilot projects need to be scaled up. The country needs some influential ‘watch dogs’ to keep these strategies on track. Too much international appraisal can cause complacency among policy makers and politicians. 12 DENIAL, DOOM, OR DESTINY? RESURGENT STIs IN HIV CARE AND PREVENTION Jeanne M. Marrazzo , University of Alabama at Birmingham, Birmingham, AL, USA Antiretroviral therapy (ART) that achieves virologic suppression essentially eliminates the risk of sexual transmission to HIV-uninfected partners, informing the hope that treatment as prevention can play a major role in crippling the HIV epidemic. Moreover, persons who appropriately use preexposure prophylaxis (PrEP) can avoid HIV acquisition, and use of the currently approved agent, tenofovir-emtricitabine (TDF-FTC), is increasing globally. As uptake of these approaches has escalated, sexual behaviors have evolved on the different timelines that defined their implementation: first in people living with HIV as increasingly powerful ART reliably effected HIV suppression, then in people at risk for HIV as PrEP was rolled out. As ART enhanced quality of life and, naturally, sexual health, increases in rates of sexually transmitted infections (STIs) were reported among people living with HIV-notably syphilis, especially among men who have sex with men (MSM). This might be considered the “first new wave” of STIs in the post-ART era. As PrEP uptake has gained traction, a “second new wave” of increasing STI incidence has gathered strength, with record rates of gonorrhea and syphilis in MSM. The high efficacy of PrEP, especially in MSM, means that individuals at risk can avoid HIV acquisition in the absence of barrier methods of protection. Critically, MSM are not the only concern. In sub-Saharan Africa, PrEP is being rolled out in settings where syndromic management is still the standard approach to STI management-clearly, a suboptimal situation. Demonstration projects of PrEP in these settings have not had the capacity or intent to evaluate concomitant shifts in STI incidence at a community level. The implications of rising STI rates require reassessment of the alignment and prioritization of HIV research funding, health policy, and community engagement and inform numerous questions. Are STIs an inevitable byproduct of biomedical HIV control, and should the answer change our view of sexual health? Do we need to think differently about management of non-HIV STIs (screening, diagnosis, treatment, partner management) in those at risk for HIV? Is high STI incidence likely to undermine success of TasP or PrEP in the long term or in certain populations? Should new approaches focus on broader spectrum prevention (agents that inhibit HIV and other viruses)? What are the broad implications, including funding and trial design, for clinical STI research? From the outset of the HIV epidemic it became clear that the virus capitalized on the immune defenses of the host to create an immune environment that would further foster availability of cellular targets and viral replication. Several studies in animal models of SIV and in humans at various stages of disease have concluded that immune activation represents an independent prognostic factor in HIV including treated disease with successful virologic suppression. Systemic inflammation and immune activation in HIV have been linked to excess risk for both AIDS and non-AIDS serious events in both untreated and treated people living with HIV (PLWH), and seem to accelerate the detrimental effect of other comorbidities such as smoking or diabetes or aging. In addition, inflammation and cellular activation can be critical in viral persistence contributing to the preservation, expansion or population shifts of the HIV viral 13 INFLAMMATION: TAMING THE FLAMES Irini Sereti , NIAID, Bethesda, MD, USA

reservoirs. The etiology of immune activation and inflammation in treated HIV is considered multifactorial encompassing residual viral replication, mucosal injury at effector sites that leads to innate immune activation and potentially dysbiosis, incomplete CD4 restoration, tissue fibrosis and coinfections. Inflammation and fibrosis in HIV are also accompanied by coagulopathy. Biomarkers that signify the degree of inflammation such as IL-6, CRP, sCD14 as well as D-dimer levels have been found in numerous studies to be strong independent predictors of morbidity and mortality in PLWH. It is though unclear if and to what extent, altering these biomarkers with anti-inflammatory or other therapies could alter clinical outcomes. Efforts to counteract the chronic inflammation in HIV have focused on the various facets of its etiology largely with small or moderate success. At the moment the best approach is treatment with antiretroviral therapy, preferably at diagnosis at early stages of disease when CD4 counts are still high, in combination with aggressive treatment of possible comorbidities. A better understanding of the etiologic pathways and how they intersect leading to chronic inflammation in HIV will be critical for improved, and efficacious, treatment interventions. 14 HV VACCINE WITH LEEP DID NOT PREVENT RECURRENT CERVICAL HSIL IN HIV-INFECTED WOMEN Cindy Firnhaber 1 , Avril Swarts 2 , Masangu Mulongo 3 , Bridgette Goeieman 3 , Sophie Williams 3 , Simon Levin 3 , Mark Faesen 3 , Pamela Michelow 4 , Timothy Wilkin 5 1 University of Colorado, Aurora, CO, USA, 2 Clinical HIV Research Unit, Johannesburg, South Africa, 3 Right to Care, Johannesburg, South Africa, 4 National Health Laboratory Service, Johannesburg, South Africa, 5 Weill Cornell Medicine, New York, NY, USA Background: Women living with HIV are at high risk for cervical HSIL and rates are especially high in sub-Saharan Africa. These women have high HSIL recurrence rates after loop electroexcision procedure (LEEP) requiring additional monitoring and treatment. More effective treatment for HSIL lesions in HIV infected women is needed. Some retrospective studies suggest that the Human Papillomavirus (HPV) vaccine used as adjuvant therapy with LEEP improves response to treatment of High-grade Squamous Intraepithelial lesions (HSIL) in HIV negative women. We evaluated the effectiveness of the HPV quadrivalent vaccine in preventing the recurrence of HSIL after LEEP in HIV infected women in Johannesburg South Africa. Methods: We performed a double-blind, randomized clinical trial that enrolled 180 HIV infected women, between the ages of 18-65 years and cervical HSIL on histology in Johannesburg South Africa according to Consort criteria. The women were excluded if they were pregnant. Women received the quadrivalent HPV or placebo vaccine (1:1) at entry, week 4, and week 26. LEEP was performed at week 4. Colposcopy and directed biopsies and cervical cytology were performed at week 26 and 52. The primary endpoint was cervical HSIL by histology or cytology at either week 26 or 52, and this was compared between arms using Chi-square analysis. Results: Participant characteristics included median age 39, median CD4 489, and 94% had HIV suppression (<200 copies/ml) on antiretroviral therapy. Of the 180 women enrolled, 179 women underwent LEEP and 174 women completed the vaccine/placebo series and had evaluable results at week 26 or 52. The proportion experiencing the primary endpoint of HSIL was similar in the vaccine and placebo groups, 53% vs. 45% (RR 1.16, 95% CI .87-1.6, P=.29). Similar results were seen when using only histologic results at 26 and 52 weeks (32% vs. 31%, RR 1.04, 95% CI .67-1.04, P=.9). HSIL recurrence was associated with a LEEP result of HSIL and positive margins on LEEP at week 4. Conclusion: This randomized, double-blind clinical trial did not find evidence to support an adjuvant role for HPV vaccination for preventing recurrent HSIL post-LEEP in women living with HIV. Recurrent HSIL was high despite virologic suppression with antiretroviral therapy. More effective treatment strategies are needed to reduce the burden of recurrent cervical HSIL in this high risk population. 15 OPTIMAL LUNG CANCER SCREENING CRITERIA AMONG PERSONS LIVING WITH HIV Subhashini A. Sellers 1 , Andrew Edmonds 1 , Catalina Ramirez 1 , Sushma Cribbs 2 , Igho Ofotokun 2 , Laurence Huang 3 , Alison Morris 4 , Meredith C. McCormack 5 , Ken M. Kunisaki 6 , Maria P. Rivera 1 , M. Brad Drummond 1 , Adaora Adimora 1

Oral Abstracts


CROI 2019

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