CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

had higher weight gain compared to those starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; among INSTIs, weight gain was greater with dolutegravir and raltegravir versus elvitegravir-containing regimens. Recent smaller analyses also report weight gain among patients with virologic suppression switched from PI- or NNRTI-containing regimens to INSTI regimens, and a minor weight increase in those switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). In summary, weight gain is common among PLWH starting ART and may occur following regimen switches. Rigorous clinical trial data is needed to confirm findings from observational cohorts, in addition to studies of potential mechanisms linking antiretroviral agents and body weight. Victor Valcour , University of California San Francisco, San Francisco, CA, USA HIV infection is a leading cause of cognitive impairment in people under the age of 60, worldwide. Historically, there was little need to differentiate cognitive disorders due to HIV from that of age-associated neurodegenerative disorders, such as Alzheimer’s disease, because few patients living with HIV survived into geriatric age groups where prevalence of these neurodegenerative disorders increase exponentially. This talk will provide recent evidence of persistent clinically meaningful cognitive challenges in patients aging with HIV. We will review likely neuropathogenic mechanisms and recent data on the typical clinical presentation. We will review data captured, primarily from clinical settings, that can inform potential interactions among HIV infection, vascular central nervous system damage, and Alzheimer’s disease as we address facts and fiction around brain aging with HIV. Addressing one of the most challenging clinical geriatric neuroHIV issues of the current time, we will discuss current knowledge around differential diagnosis related to cognitive disorders in people living with HIV over the age of 60 years. only proper use will be associated with protection against HIV-infection. PrEP failures have many causes which need to be clearly diagnosed. System failures refer to the lack or limited access to PrEP because of unavailability, lack of awareness among people at risk and health care providers, and cost. Governments should endorse WHO guidelines and offer PrEP to those who need it. Doctors failures refer to insufficient knowledge of PrEP with the failure to rule out HIV-infection when starting or renewing PrEP, or reluctance to prescribe PrEP. People failures are mostly due to the deferred or improper use of PrEP since strict adherence to PrEP is critical for effectiveness. Assay failures refer to the challenges of HIV diagnosis due to the low sensitivity of HIV tests during the first days/weeks following HIV acquisition, the impact of TDF/FTC use on HIV antibody and viral load assays and also the challenge of ruling out HIV-infection in case of false positive serologic assays on PrEP. Drugs failures which are the most feared causes of PrEP failure remain rare with only a handful of breakthrough HIV-infections in people with good adherence to PrEP. These cases are potentially due to the acquisition of a virus with TDF and/or FTC resistance, exposure to a very high HIV inoculum, pharmacokinetic variability in blood and/or tissues, drug drug interactions, concomitant STIs or altered microbiota. PrEP failures can lead to drug resistance when started or maintained in a person with HIV-infection. In clinical trials, most cases of HIV-infection with resistance occurred when PrEP was started in someone with undiagnosed HIV- infection. In case of HIV-infection antiretroviral therapy including drugs with a high genetic barrier to resistance (boosted darunavir, dolutegravir, bictegravir) should be immediately initiated pending the results of a genotypic resistance test. Overall, true biomedical failures of PrEP remain rare, but these cases should be thoroughly investigated to understand the reasons of PrEP failures. implementation an effectiveness that was better than in clinical trials. However, despite its high effectiveness, and because of its increased use, a number of PrEP failures have been reported highlighting that, as any preventive tool,

Additionally, several 2DR have demonstrated suboptimal efficacy with high rates of emergency drug resistance at virological failure. Unboosted integrase inhibitors with a high barrier to resistance offer the option of non-PI-based 2DR and, to date, dolutegravir/rilpivirine and dolutegravir/lamivudine have demonstrated high efficacy in stable switch and first-line therapy, respectively; these combinations, however, face the challenge proving efficacy, bu t the challenge of shifting the paradigm of 3DR that has been central to practice for over 2 decades. Current guidelines still prefer 3DR – howmuch evidence is required for 2DR to be elevated from ‘alternative’ status? Must 2DR be better than 3DR in some way or simply similar? With injectable options on the horizon we need to consider not only how to best use 2DR, but how to deliver treatment in new way. Who will want to trade daily pills for regular injections and how can we integrate that into busy clinical practice? Many questions about 2DR remain unanswered, including the impact of baseline resistance, efficacy in suboptimal adherence and the importance of compartment penetration. The balance between embracing progress and employing caution when 3DR has delivered so much is a tricky one, but the decisions we help our patients make should be considered within a robust ethical framework. We need to ensure that future studies fill the gaps in our knowledge so we can incorporate 2DR into our practice in the safest and most appropriate manner. Asa Radix , Callen–Lorde Community Health Center, New York, NY, USA Transgender and gender diverse youth (i.e., those whose gender identity does not align with their sex assigned at birth), especially transfeminine youth of color, face high rates of verbal and physical violence, unsafe school environments, family rejection and homelessness. Stigma and discrimination against transgender people have been linked to adverse health outcomes, such as low self-esteem, depression and substance use, which are inextricably tied to HIV vulnerability. Although data on HIV incidence and prevalence are limited for transgender youth, young transgender women of color are disproportionately impacted. Few data exist for transgender men and gender diverse individuals assigned female at birth, however trans men who have sex with cisgender men and engage in sexual risk behaviors such as condomless sex, are at heightened risk for HIV infection. Transgender youth face unmet medical needs, including access to gender-affirming care and HIV/STI testing, counseling and prevention services. Research has shown underutilization of pre-exposure prophylaxis (PrEP) among those at risk for HIV. This presentation will review recent epidemiologic data related to HIV in transgender and gender diverse youth and describe current and evolving developmentally appropriate and culturally sensitive HIV prevention interventions. To be successful clinical settings should seek to engender resilience through self-acceptance and increased sense of belonging, provide navigation of legal and other structural barriers to care and offer avenues for peer support and social activism. The Callen-Lorde Community Health Center in New York City operates one of the largest and longest-running transgender clinic programs in the United States, serving over 4000 clients (including 1,215 who are aged 24 and under) though on-site and mobile health services. The clinic illustrates best practices for HIV prevention including implementation of trauma-informed medical care, multidisciplinary teams with expertise in transgender medicine, facilitated referrals to surgeons and specialists, comprehensive sexual health education and a robust PrEP program. Adolescent girls and young women (AGYW) in sub-Saharan Africa (SSA) are at substantial risk for HIV infection. Oral PrEP has the potential to provide HIV protection if used consistently. Two blinded efficacy trials of oral PrEP in women in SSA did not show evidence of HIV protection in AGYW because of low adherence in these trials; adherence was lowest in AGYW. These findings led to concerns that AGYW did not perceive their risk or did not want to use HIV prevention products. Recent open-label demonstration studies of oral PrEP in AGYW however have shown that young women do perceive their risk and that uptake of open-label oral PrEP is high. Challenges remain, however with taking a pill a day. This presentation will present updates on findings from open-label studies about uptake and continuation of oral PrEP in AGYW, as well as strategies that have been shown to improve PrEP continuation. Progress on expanding national programmes and lessons learned from these will also be Sinead Delany-Moretlwe , Wits Reproductive Health and HIV Institute, Johannesburg, South Africa

159 I KEEP FORGETTING: HIV, AGING, AND COGNITIVE DISORDERS

Oral Abstracts

162 YOUNG TRANSGENDER INDIVIDUALS

160 PrEP FAILURES: DIAGNOSIS, RESISTANCE, AND TREATMENT Jean-Michel Molina , Hôpital Saint-Louis, Paris, France PrEP with TDF/FTC has shown in demonstration projects and real life

163 ENGAGING YOUNG WOMEN IN SUB-SAHARAN AFRICA

161 CAN TWO DRUGS TANGO: THE ROLE OF DUAL THERAPY Laura Waters , Mortimer Market Centre, London, UK

In an era of largely well-tolerated antiretrovirals with high virological efficacy, the new ‘battle’ is that of two vs three drug regimens (2DR vs 3DR). The majority of studied 2DR have been boosted-protease inhibitor based so, despite any possible benefit of fewer drugs, hampered by the limitations of the PI class including tolerability, long-term toxicity and extensive drug-drug interactions.

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CROI 2019