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Session 2: Role of STI management in HIV prevention

Tracks
Wednesday, 22 May
Wednesday, May 22, 2019
14:00 - 16:10

Speaker

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Dr Gary Whitlock
Consultant Physician
Dean Street Clinic, Chelsea & Westminster Hospital

New approaches to STI management

14:00 - 14:20
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Dr Cécile Bébéar
University of Bordeaux and Bordeaux University Hospital

Interplay between PrEP and STI

14:20 - 14:35
Dr. Manuel Reiriz Rojas
Director
Adhara, Asociación VIH/sida

First results after 52 weeks of informal PrEP use in a cohort of MSM in Southern Spain.

Abstract

Background
Despite the fact that Southern Spain has similar HIV incidences than Eastern Europe, PrEP use is blocked, both nationwide and by the Andalusian Regional Government. Between January 2018 and December 2018, a sample of 167 MSM with high risk practices has begun to be part of a cohort of informal PrEP users in this region. With the objective of making safer the use of PrEP and offer a basic tool in this MSM cohort, Sevilla Checkpoint implemented PrevenPrEP, a new program that assess regular checkouts and follow up to people using this biomedical strategy on their own.
Methods
From the opening of Sevilla Checkpoint in November 2017, 419 MSM showed interest in the use of PrEP. Furthermore, 67% of them declared unprotected anal sex and 61 were chemsex users. In January 2018, Sevilla Checkpoint began to work on this MSM cohort to enforce the UNAIDS combined preventive strategies against HIV.
The educators firstly evaluate the real risk of the different potential prevenPrEP users. Those selected, were first of all tested against HIV/STIs by using PCR technology and they were required a general blood analytic from their GPs to evaluate the kidney and liver function. While users were taking PrEP, Sevilla Checkpoint tested them against HIV/STIs.
Results
A total of 167 MSM were included in the program; 152 of them use daily PrEP and 15 event-driven. All of them showed a normal biochemistry parameters and no initial HIV/STIs infections. The general characteristics of our PrevenPrEP users was similar to those shown by previous studies; an MSM of 34 years of age, 58% of them with a university degree and the rest -42%- secondary studies. 85% of users showed previous HIV tests, with an average of 9 times per user. Regarding anal sex, 78,4% never used condoms during sexual intercourse with an average of 32 different sexual partners in the last 6 months. Moreover, 15,6% of them were chemsex users. Finally, regarding HIV, no infection was detected in this cohort and 6,6% of them were reactive against Chlamydia, 5,4% against Gonorrhoea, and 1,2% against Syphilis.
Conslusion
These results show that there is a cohort of MSM in Seville who are interested in PrEP and whose sexual practices justify the use of it to protect themselves of HIV infections. As we expected, there was not any new HIV infections in this cohort. On the other hand, the percentage of STIs diagnosed was approximately 50% lower than those people tested in our community center who are not using PrEP, showing the importance of STIs monitorization to prevent new infections.
The community centers as Sevilla Checkpoint have the capacity to offer proffessional advise and monitoring services to informal PrEP users and prove to be strong candidates to offer these services when PrEP will be implemented by the Spanish Government.
Dr. Carole Seguin-Devaux
Deputy Head of the Infectious Diseases Research Unit
Luxembourg Institute Of Health

European surveillance of HIV drug resistance to NRTI, NNRTI and INSTI in newly diagnosed individuals using next-generation sequencing

Abstract

Background
Although European guidelines have shifted towards INSTIs as first line therapy, NNRTIs are still frequently used in particular in Central and Eastern Europe. Due to its multicenter and representative nature, the surveillance SPREAD program is an ideal framework to investigate the prevalence of the minority resistant variants to NRTI, NNRTI and INSTI in newly diagnosed individuals in Europe.

Material and Methods
A sample of 275 individuals newly diagnosed therapy-naïve in 2012/2013 were randomly selected from the European SPREAD database from 12 countries: Belgium n=20; Bulgaria n=40; Croatia n=25; Cyprus n=18; Finland n=20; France n=20; Greece n=30; Israel n=15; Lithuania n=22; Luxembourg n=22; Poland n=23; Slovenia n=20 and from Russia (n=24). Ultradeep RT sequencing was performed using a 454 FLX Genome Sequencer (Roche, Manheim) and IN Sequencing was performed on an Illumina MiSeq platform (Illumina, USA). Sequencing files were imported into CLC GenomicWorkbench (v.10.1.1). Sequences were checked for quality and trimmed using a minimum PHRED score 20. Low frequent variant calling was performed with a significance of 1% and a minimum coverage of 500 reads. For RT interpretation the WHO list for surveillance of drug resistance mutations was used. For IN all substitutions relative to HXB2, and included the mutation scoring of Stanford HIVdb v8.7 were listed.

Results
A total of 254 samples were successfully sequenced for RT and 214 for IN. The majority was male and of European origin, infected with various HIV subtypes. Based on the WHO list, the prevalence of NRTI and NNRTI resistance mutations with an abundance above 20% of the viral population was 3.5% and 7%, respectively, in agreement with Sanger sequencing data from the SPREAD program. The total of low abundance variants (<20%) was 26 (10.2%) for NRTI-resistance mutations and 17 (6.7%) for NNRTI-resistance mutations. The majority was detected at a prevalence level below 5%: 15 (5.9%) and 13 (5.1%) for NRTI and NNRTI mutations, respectively. Resistance mutations between 5 and 20% prevalence that may have an impact on the virologic outcome include: K65R (n=5), M184V (n=2), T215S (n=3), K219R (n=1) for NRTI and K103R (n=1), V179E (n=1), G190E (n=1) for NNRTI. No INSTI signature mutations were observed above the cut-off of 20%. Only at a detection level below 5%, S147G was detected in 2 individuals and Y143C in one individual. Presence of Y143C was found in combination with L74M, E157Q and S230N. Non-polymorphic mutation E138K was observed as minority variant in 4 individuals, only once in combination with L74M. Polymorphic mutation T97A was detected in 3 individuals but always as single mutation. Other frequent detected polymorphic mutations were E157Q (n=12; 9/12 subtype B), L74M or L74V (n=46; 31/46 subtype A) and S230N (n=36; 35/36 subtype B).

Conclusions
A significant proportion of low abundance transmitted drug resistance to NRTI and NNRTI was detected in this representative set of newly diagnosed therapy-naïve HIV-patients from Europe. We found no evidence of increasing TDR for INSTIs that would support the need to perform integrase genotyping before initiating INSTI therapy. Continued surveillance of INSTI resistance is nevertheless warranted.
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Dr. Evangelia Georgia Kostaki
Postdoctoral Researcher
Medical School, National and Kapodistrian University of Athens

Molecular analysis suggests post-migration HIV-1 acquisition among migrants in Paris, France

Abstract

Background: A considerable proportion of people diagnosed with HIV-1 in Europe the last few years, are migrants. We aimed to trace the geographic origin of HIV-1 acquisition for migrants in Paris, France, using current state-of-the-art molecular epidemiology methods.

Materials & Methods: We studied 1,582 and 302 sequences of CRF02_AG and subtype A1, respectively, available in the pol region, isolated from HIV-1 diagnosed patients in Paris during 2002-2016. These data were derived from a total sample of 5,553 sequences. HIV-1 subtyping was carried out using automated subtyping tools (COMET, REGA). We analyzed phylogenetically the subtype A1 sequences from migrants (N=58) along with all the available A1 sequences from non-migrants in Paris (N=244), a random set of globally sampled A1 sequences (N=1,400) and the most closely related sequences to our study population (migrants & non-migrants from Paris) using the HIV BLAST tool (N=744), used as references. We also analyzed 273 and 1,309 CRF02_AG sequences from migrants and non-migrants from Paris, respectively, along with all the available globally sampled CRF02_AG sequences (N=4,013), as references. Local transmission networks (LTNs) were phylogenetic clusters including sequences from France at proportions >70%, receiving bootstrap value >75% or SH-support >0.9. Phylogenetic trees were estimated by the maximum likelihood method (RAxML, FastTree). The origin of HIV-transmissions was traced by phylogeographic analysis using the criterion of parsimony (Mesquite).

Results: Subtype A1 (N=302; 5.4%) and CRF02_AG (N=1,582; 28.5%) were the most prevalent non-B clades in Paris. The number of LTNs for subtype A1 was 42 with a range of 2 to 8 sequences. For CRF02_AG we found 166 LTNs consisting of 2 to 15 sequences and two large ones including 26 and 139 sequences. Phylogenetic analysis also revealed that 18 (31.0%) A1 sequences from migrants and 60 (30.5%) from non-migrants clustered within LTNs. For CRF02_AG, 101 (37.0%) sequences from migrants, and 411 (38.7%) from non-migrants fell within LTNs. The distribution of transmission risk groups in migrants infected with A1 strains was: heterosexuals (N=47; 81%), MSM (N=4; 6.9%), and others/unknowns (N=7; 12.1%). For CRF02_AG, it was: heterosexuals (N=191; 70.0%), MSM (N=42; 15.4%), and others/unknowns (N=40; 14.6%). Notably, the proportion of migrant MSM within CRF02_AG LTNs was significantly higher (85.7%) than the corresponding proportion for the heterosexuals (28.3%) (p<0.001). Phylogeographic analysis showed that 23.3% and 33.3% of the subtype A1 and CRF02_AG HIV-transmissions within migrants, respectively, occurred locally.

Conclusions: We found that 23.3% and 33.3% of subtype A1 and CRF02_AG HIV-transmissions within migrants, respectively, originated in Paris/France. For CRF02_AG we found that transmissions within LTNs were associated with MSM transmission risk group. The proportions of putative local transmissions for these subtypes were similar for the non-migrant population, pointing out that local transmissions within migrants and non-migrants occur at similar rates. Given the low coverage of our sampling we expect that the proportion of local transmissions will be higher for both subgroups. This is one of the few molecular studies highlighting that even non-B transmissions occur locally at similar rates for migrants and non-migrants in Paris.
PhD Marta Pingarilho
Researcher
Institute of Hygiene and Tropical Medicine

TRENDS OF TRANSMITTED AND ACQUIRED HIV-1 DRUG RESISTANCE IN PATIENTS FOLLOWED IN PORTUGUESE HOSPITALS BETWEEN 2001 AND 2017

Abstract

Background: By the end of 2017, there were approximately 36.9 million people living with HIV and 21.7 million people were receiving antiretroviral (ARV) therapy. Drug resistance to ARV is still a limitation for the control of HIV-1 infection. Despite new ARVs having higher genetic barriers, some patients continue to virologically fail due to transmitted (TDR) or acquired (ADR) resistance that can harm the efficacy of ARV regimens. The goals of this study were to describe and analyse the trends of TDR and ADR in patients clinically followed in Portuguese hospitals between 2001 and 2017.
Methods: A total of 11911 HIV-1 patients followed in Portuguese hospitals were included in the study. Patients were categorized into drug naïve (DN) and treated patients (TP). TDR was defined by the presence of one or more surveillance drug resistance mutations according to the World Health Organization (WHO) 2009 surveillance list. Genotypic resistance to ART drugs was evaluated using the Standford HIVdb v8.04. Logistic regression was used to characterize prevalence by calendar year, drug class and demographic and clinical factors (SPSS software).
Results: Most participants were male (64.6% for DN and 67.3% for TP). The median age of patients at the time of genotyping was 38.0 (IQR: 31.0-48.0) and 39.0 (IQR: 33.0-46.0) years for DN and TP, respectively. DN and TP were predominantly infected with subtype B virus (36.7% and 42.6%, respectively), followed by subtype G (25.2% and 32.8%, respectively). Most of the patients were born in Portugal (34.7% for DN and 29.9% for TP) followed by countries in Sub-Saharan Africa (13.3% for DN and 11.1% for TP). Overall, the prevalence of TDR was 9.4% (95%CI: 8.8-10.1) and of ADR was 69.0% (95%CI: 67.6-70.5). The prevalence of TDR increased from 7.9% in 2003 to 13.1% (p for trend<0.001) in 2017, whereas the prevalence of ADR decreased from 86.6% in 2001 to 51.0% (p for trend<0.001) in 2017. The prevalence of nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs) mutations for drug naïve patients increased from 5.6% to 6.7% (p for trend=0.002) and 2.9% to 8.9% (p for trend<0.001) between 2003 and 2017, respectively. For protease inhibitors (PIs), TDR decreased from 4.0% in 2003 to 2.2 (p for trend=0.985) in 2017. ADR mutations declined for all ARV classes over time (pfor trend<0.001). The most frequently detected TDR mutations were K103N/S (3.2%), M41L (1.6%) and M184V/I (1.3%). For treated patients, the most common mutations found were M184V/I (45.3%), K103N (26.0%) and T215Y/F (17.4%). Predicted phenotypic high-level resistance to first line ARV drugs presented the highest value to NNRTIs with Nevirapine (4.7%) and Efavirenz (4.0%), for drug-naïve patients and the highest values to NRTIs with Emtricitabine and Lamivudine (45.3%) for treated patients.
Conclusion: While ADR is decreasing since 2001, TDR has been increasing, reaching moderate rate of 13.1% in 2017. It is urgent to develop public health programs to monitor levels and patterns of TDR in newly diagnosed patients.

Collaborators of the Portuguese HIV-1 Resistance Study Group: Kamal Mansinho, Ana Cláudia Miranda, Isabel Aldir, Fernando Ventura, Jaime Nina, Fernando Borges, Emília Valadas, Manuela Doroana, Francisco Antunes, Nuno Marques, Maria João Aleixo, Maria João Águas, Júlio Botas, Patrícia Pacheco, Micaela Caixeiro, Teresa Branco, José Vera, Inês Vaz Pinto, José Poças, Joana Sá, Luís Duque, António Diniz, Ana Mineiro, Flora Gomes, Carlos Santos, Domitília Faria, Paula Fonseca, Paula Proença, Luís Tavares, Cristina Guerreiro, Jorge Narciso, Telo Faria, Eugénio Teófilo, Sofia Pinheiro, Isabel Germano, Umbelina Caixas, Nancy Faria, Ana Paula Reis, Margarida Bentes Jesus, Graça Amaro, Fausto Roxo, Ricardo Abreu and Isabel Neves.

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