CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

159 INTEGRATING NEW ANTIRETROVIRAL THERAPIES Chloe Orkin , Barts Health NHS Trust, London, UK

delays (up to 9 years) between licensing in adults and children. Dosage for commonly used drugs are still lacking in neonates and young children, i.e. abacavir is only licensed from 3 months of age and P1093, a dosing study of dolutegravir is still in progress. Lack of data and appropriate formulations prevents harmonization of adult and pediatric guidelines. Strategies to accelerate development includes modeling of dosing and adapting study design to facilitate rapid enrollment, this includes addressing tuberculosis, still a common infection. Studies to compare regimens and drug sequencing are uncommon in children, careful extrapolation of adult data for efficacy will inform pediatric practice in planning standard regimens and placing new drugs in the therapy sequence. Most children are infected with drug resistant HIV. As adult treatment programs mature, infants of mothers failing to suppress on PI are particularly vulnerable. Despite lopinavir/ritonavir (the preferred first line therapy for young children) having a high resistance threshold, children develop resistance, where resistance testing is unavailable consideration should be given to what the appropriate third line should be. Using dolutegravir as a first line regimen in mothers may compromise this drug in first line therapy in some infants. Pediatricians share excitement for long acting injectable drugs, their best use may be to prevent HIV infection in infants. Under these circumstances, resistance should be studied in order to predict its effect on initial therapy. As new drugs and drug combinations are developed tolerability and ease of use should be actively studied as should its contribution to therapy success. 162 TRANSITIONING TO NEW GENERIC ANTIRETROVIRALS IN SUB-SAHARAN AFRICA Tendani Gaolathe , Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana The pricing of drugs has influenced national ARV treatment guidelines in many Sub Saharan countries. The new possibility of integrase inhibitors - mostly dolutegravir (DTG) as first line was becoming a reality. This development called for policy adoption and introduction into national treatment guidelines, planning for roll-out, streamlining, and strengthening supply chain systems; all in the context of the newly adopted ‘treat all guidelines.’ For most SSA countries, integrase inhibitor use has been limited to 3rd line and beyond treatment failures. However with the anticipation that the cost of the FDC containing TDF/FTC and DTG will be cheaper than the current price of TDF/FTC/EFV 600 in low and middle income African countries and the advantages conveyed by the resistance barrier of this regimen a move to first line therapy was proposed. The generic drug competition and large volumes anticipated, especially with the adoption of the Treat all program in many SSA countries would even lower the prices more. Botswana, Kenya, South Africa, Nigeria and Uganda have been noted as the early adopters of integrase inhibitors as first line in their national formularies. By end of November 2017, the integrase inhibitor DTG had made it as first line into the national formulary and procurements done. Similarly other countries have introduced first line integrase inhibitor-based therapy into the national guidelines but were at different stages of planning. According to WHO, by November 2017 more than 20 countries had included DTG as a first line option With all the excitement, there is also uncertainty with DTG as a first line option, as there is limited evidence on DTG and TB (a common OI in SSA) and outcomes in pregnancy. For other countries there remained concerns about low availability of the low cost generic drugs, and the time and effort needed for approvals and registration in countries until the latter part of 2017. For the HIV-infected clients who are initiating antiretroviral therapy the challenges are few, but for transitioning, or treatment switches (for cost savings), this process has to be managed carefully. 163 THE OPIOID EPIDEMIC AND INFECTIOUS DISEASES: A PUBLIC HEALTH CRISIS Sally Hodder , West Virginia Clinical and Translational Science Institute, Morgantown, WV, USA The accelerating death rate due to drug overdose has been widely publicized in the popular media, yet there lurks an underlying veiled scourge of death and morbidity due to emergent infectious disease epidemics that are a consequence of the opioid epidemic. In the United States in 2016, there were more than 60,000 drug overdose deaths. To that toll must be added the nearly 20,000 additional deaths from viral hepatitis. Deaths in the U.S. due to the opioid epidemic exceed those due to HIV at the height of the AIDS epidemic in the U.S. Reported cases of acute hepatitis C increased nearly 3-fold from 2010 to 2015, largely due to increases in injection drug use. There was a more than 20%

The ‘pipeline’ of candidate anti-HIV drugs includes novel classes, novel mechanisms of action, biologics and broadly neutralizing monoclonal antibodies. Formulations under development include a diverse range of options such as long-acting oral weekly products and implants capable of providing treatment for several months. Patient acceptability survey outcomes of LA/ER injectable Cabotegravir-Rilpivirine in phase III trials have been very positive. Importantly, drugs are also being developed for patients with extensive anti-viral resistance. Moving towards the future, it is important to examine the efficacy of current ART regimes in first line therapy and beyond, including when switching virologically suppressed patients. In 2018, is efficacy driven mainly by virological factors (high baseline viral load and emergence of resistance) or by tolerability and simplicity? How do we address the data gaps in RCTs, which largely enroll well, young male patients and very few women, transgender, co-infected, complex or ethnically diverse patients? With a future moving towards reducing drug exposure can we ‘simplify’ ART? Near-normal life expectancy of people living with HIV makes it ever more important to use regimens that safeguard against future comorbidity. Advances in the triple therapy TAF-based backbone have reduced treatment-related discontinuations related to bone and renal toxicity, while maintaining efficacy rates of > 90% in treatment-naïve studies. Second generation integrase inhibitors, recommended in the first-line guidelines of ALL well-resourced settings, have reduced emergent resistance toward zero and offer options which avoid booster-related drug interactions. Successful ART simplification is determined by critical pharmacological, biological and behavioural factors including potency, the genetic barrier, adherence and duration of suppression. Attempts to reduce toxicity by using certain two-drug (2DR) combinations in first line therapy and in switch studies have produced unexpectedly disappointing results. However, other 2DR combinations (such as bPI+3TC and NNRTI+INSTI) have demonstrated efficacy similar to triple therapy in switch studies. Large first-line 2DR studies will soon report outcomes. Some data on the safety benefits of 2DR regimens vs TDF-containing regimes have been reported but more are needed. Improving simplicity, tolerability, acceptability while reducing toxicity will be key areas of focus for the ART regimes of the future. Small molecule inhibitors of HIV-1 replication have transformed antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP). Despite these successes, for many persons living with or at risk of acquiring HIV infection, the burden of taking daily medication poses significant challenges. Monoclonal antibodies that neutralize a broad range of HIV-1 isolates (bNAbs) may provide a long- acting alternative to daily oral therapy. The antiviral activity and preventive efficacy of several bNAbs administered singly or in combination have been demonstrated in non-human primate models and pilot human clinical trials, and large-scale efficacy trials of one bNAb for PrEP are currently underway. Significant challenges remain, however, in translating these promising preliminary results into practical, scalable and affordable preventive and therapeutic agents. These include identifying suitable combinations, potential immunogenicity of modified or synthetic bNAbs, developing formulations that allow self-administration, and process improvements that reduce the costs of manufacture to make bNAbs cost-effective alternatives to daily oral single- tablet regimens. 161 ANTIRETROVIRAL THERAPY IN CHILDREN: PRESENT CHALLENGES, FUTURE OPPORTUNITIES Helena Rabie , Stellenbosch University, Cape Town, South Africa Despite the reduction in mother to child transmission each year 100000– 220000 new HIV infections still occur in children below 14 years of age globally, with only 43% accessing antiretroviral therapy. The complexities of diagnosis, linkage to care and retention are known but all children have unique therapeutic challenges. High suppression rates in adults are not mirrored in children. In low- middle-income settings only 62.5% of children are suppressed after 12 months on therapy. Unsuitable formulations and poor access to protease inhibitors (PI) are contributory. Neonates, especially if premature or low birth weight, have unique dosing requirement and adolescents particular adherence challenges. As each developmental stage requires dosing information there are considerable 160 BROADLY NEUTRALIZING ANTIBODIES FOR HIV PREVENTION AND TREATMENT: DREAM OR PIPE DREAM? Daniel R. Kuritzkes , Brigham and Women’s Hospital, Boston, MA, USA

Oral Abstracts

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CROI 2018