CROI 2019 Abstract eBook
524 RECTAL AND SEMINAL HIV-1 RNA DECAY IN INFECTED MSM INITIATING WITH DTG/ABC/3TC Marta Fernández 1 , Vanesa Agulló 1 , José A. García 1 , Sergio Padilla 1 , Javier García- Abellán 1 , Victoria Ortiz de la Tabla 2 , Félix Gutiérrez 1 , Maria Del Mar Masia 1 1 Hospital General Universitario de Elche, Elche, Spain, 2 Hospital Universitario San Juan De Alicante, Alicante, Spain Background: Antiretroviral therapy (ART) reduces significantly the risk of HIV-1 transmission. However, after starting ART, it is not clearly established at what time the protective effect of ART is achieved in reservoirs, e.g. the rectum or semen, which is particularly important in men who have sex with men (MSM). We carried out this study to quantify HIV-1 RNA decay in rectal mucosa and semen over 64 weeks (64w) in ART-naïve HIV-infected MSM starting dolutegravir+abacavir+lamivudine (DTG/ABC/3TC). Methods: Longitudinal cohort study of ART-naïve HIV-infected MSM. Rectal mucosal sampling was performed by high-resolution anoscopy (HRA) when possible, or by insertion of swab directly into rectum. Seminal plasma was obtained by centrifugation of semen collected at home within 2 hours before. HIV-1 RNA quantification (COBAS® Ampliprep/Taqman) of rectal mucosa and seminal plasma samples was performed at day 1 of initiating-ART (baseline) and every 4 weeks until w20 (all) and w64 (6 of 12). Results: 118 plasma, 117 rectal (86-HRA and 31-direct) and 89 seminal samples from 12 MSM, with median (IQR) age 36 (32-42) years and median baseline-CD4+ 465 (411-520) cell/μL, were included. At baseline, HIV-1 RNA was detectable in all plasma, seminal and 10 of 12 rectal samples with median viral load (VL) of 4.58 (4.32-4.84) log 10 copies/mL, 4.10 (3.59-4.44) log 10 cp/mL and 4.54 (3.82-5.11) log 10 cp/swab, respectively. All participants achieved plasma virologic suppression by w20 (7 of them by w4) (Figure). At w20, HIV-1 RNA was detectable in 5 of 12 seminal and 6 of 12 rectal samples with median VL of 2.50 (2.08-2.73) log 10 cp/mL and 2.24 (2.14-2.46) log 10 cp/swab, respectively. Of them, 3 seminal and 3 rectal samples were from aviremic individuals at w4. Median w20-CD4+ was 678 (532-797) cell/µL. At w64, HIV-1 RNA was only detectable in 1 of 6 seminal (VL=2,26 log 10 cp/mL) and 1 of 6 rectal (VL=1,81 log 10 cp/swab) samples. Conclusion: Viral decay after initiating DTG/ABC/3TC is slower in rectal mucosa and semen than in plasma. Half of the patients achieve undetectable HIV-1 RNA level in secretions at six months, although in some patients viral shedding persists up to one year.
by integrating local specificities of HIV epidemiology and the evolution of drug resistance. Methods: MARISA is a compartmental model built to capture the emergence and spread of NNRTI resistance in South Africa in 2005-2016. A first dimension accounts for the continuum of care: infection, diagnosis, first-line treatment with suppression or failure, and second-line treatment. Other dimensions include: disease progression (CD4 counts), NNRTI resistance, and gender. Model parameters are informed using data from the IeDEA-SA cohorts and literature estimates, or fitted using outputs from the Thembisa/UNAIDS models. Counter- factual scenarios are examined to assess the impact of increased treatment rates, earlier implementation of the treat-all policy, early switch to second-line treatment in case of failure, and drug-resistance testing of ART initiators. Results: MARISA can reproduce the time trends of HIV in South Africa in 2005-2016, with a decrease of new infections, undiagnosed individuals, and AIDS-related deaths (Fig 1). It also captures the dynamics of NNRTI resistance spread: a steady increase of acquired drug resistance (ADR, affecting 83% of individuals failing first-line treatment in 2016), and of transmitted drug resistance (TDR, reaching 7% of ART initiators in 2016). During that period, increasing treatment coverage would have resulted in fewer new infections and deaths, at the cost of higher TDR (+34% in 2016 for doubling the treatment rate). Earlier implementation of the treat-all policy by 5 years would have had a similar effect. Conversely, improving switching to second-line treatment would have led to lower TDR (-18% in 2016 for doubling the switching rate) and fewer new infections and deaths. Implementing baseline drug resistance testing would have had little impact. Conclusion: A rapid ART scale-up and delayed switching to second-line treatment were the key drivers of the observed spread of NNRTI-resistance in South Africa. Timely switch to second-line ART would have reduced but not prevented the spread of NNRTI resistance.
525 MODELING ANTIRETROVIRAL DRUG RESISTANCE IN SOUTH AFRICA, THE MARISA PROJECT Anthony Hauser 1 , Katharina Kusejko 2 , Leigh F. Johnson 3 , Fardo Goldstein 1 , Julien Riou 1 , Gilles Wandeler 4 , Matthias Egger 1 , Roger Kouyos 2 1 Institute of Social and Preventive Medicine, Bern, Switzerland, 2 University Hospital Zurich, Zurich, Switzerland, 3 University of Cape Town, Cape Town, South Africa, 4 University Hospital of Bern, Bern, Switzerland Background: The scale-up of antiretroviral therapy (ART) from 2004 in South Africa substantially reduced AIDS-related deaths and new HIV infections. However, its success is threatened by the emergence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). In this context, the MARISA project (Modelling Antiretroviral drug Resistance In South Africa) aims at investigating the time trends and driving factors of NNRTI resistance
526 INTEGRASE AND OTHER TRANSMITTED HIV DRUG RESISTANCE: 23 US JURISDICTIONS, 2013-2016 Robert P. McClung , Cheryl B. Ocfemia, Neeraja Saduvala, Alexandra M. Oster, Walid Heneine, Jeffrey A. Johnson, Angela L. Hernandez CDC, Atlanta, GA, USA Background: Drug resistance testing based on protease (PR) and reverse transcriptase (RT) gene mutations is recommended for all patients at entry to HIV care and should include testing for integrase (IN) mutations when transmitted resistance to integrase strand transfer inhibitors (INSTIs) is a concern. HIV sequence data from drug resistance tests are reported to the U.S. National HIV Surveillance System (NHSS) as a part of routine surveillance activities. We analyzed data from 2013−2016 to understand trends in HIV
CROI 2019 197
Made with FlippingBook - Online Brochure Maker