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1. Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Author

Crichton, Siobhan, Belfrage, Eric, Collins, Intira Jeanne, Doerholt, Katja, Judd, Ali, Le Coeur, Sophie, Spoulou, Vana, Goodall, Ruth, Scherpbier, Henriette, Smit, Colette, Goetghebuer, Tessa, Gibb, Diana M., Noguera, Antoni, Luisa Navarro, Maria, Tomas Ramos, Jose, Galli, Luisa, Giaquinto, Carlo, Thorne, Claire, Santa Ansone, Marczynska, Magdalena, Okhonskaia, Liubov, de Tejada, Begona Martinez, Jourdain, Gonzague, Decker, Luc, Ene, Luminita, Hainaut, Marc, Van der Kelen, Evelyne, Delforge, Marc, de Martino, Maurizio, Tovo, Pier Angelo, Patrizia, Osimani, Larovere, Domenico, Ruggeri, Maurizio, Faldella, Giacomo, Baldi, Francesco, Badolato, Raffaele, Montagnani, Carlotta, Venturini, Elisabetta, Lisi, Catiuscia, Di Biagio, Antonio, Taramasso, Lucia, Giacomet, Vania, Erba, Paola, Esposito, Susanna, Lipreri, Rita, Salvini, Filippo, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, Lo Vecchio, Andrea, Rampon, Osvalda, Dona, Daniele, Romano, Amelia, Dodi, Icilio, Maccabruni, Anna, Consolini, Rita, Bernardi, Stefania, Kuekou, Hyppolite Tchidjou, Genovese, Orazio, Olmeo, Paolina, Cristiano, Letizia, Mazza, Antonio, Gabiano, Clara, Garazzino, Silvia, Pellegatta, Antonio, Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S., V, van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-de Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A., I, Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, E., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, Jolanta, Pokorska-Spiewak, Maria, Oldakowska, Agnieszka, Zawadka, Konrad, Coupland, Urszula, Doroba, Malgorzata, Voronin, Evgeny, Miloenko, Milana, Labutina, Svetlana, Soler-Palacin, Pere, Antoinette Frick, Maria, Perez-Hoyos, Santiago, Mur, Antonio, Lopez, Nuria, Mendez, Maria, Mayol, Lluis, Vallmanya, Teresa, Calavia, Olga, Garcia, Lourdes, Coll, Maite, Pineda, Valenti, Rius, Neus, Rovira, Nuria, Duenas, Joaquin, Gamell, Anna, Fortuny, Claudia, Noguera-Julian, Antoni, Jose Mellado, Maria, Escosa, Luis, Garcia Hortelano, Milagros, Sainz, Talia, Isabel Gonzalez-Tome, Maria, Rojo, Pablo, Blazquez, Daniel, Prieto, Luis, Guillen, Sara, Saavedra, Jesus, Santos, Mar, Angeles Munoz, Ma, Ruiz, Beatriz, Fernandez Mc Phee, Carolina, Jimenez de Ory, Santiago, Alvarez, Susana, Angel Roa, Miguel, Beceiro, Jose, Martinez, Jorge, Badillo, Katie, Apilanez, Miren, Pocheville, Itziar, Garrote, Elisa, Colino, Elena, Gomez Sirvent, Jorge, Garzon, Monica, Roman, Vicente, Montesdeoca, Abian, Mateo, Mercedes, Jose Munoz, Maria, Angulo, Raquel, Neth, Olaf, Falcon, Lola, Terol, Pedro, Luis Santos, Juan, Moreno, David, Lendinez, Francisco, Grande, Ana, Jose Romero, Francisco, Perez, Carlos, Lillo, Miguel, Losada, Begona, Herranz, Mercedes, Bustillo, Matilde, Guerrero, Carmelo, Collado, Pilar, Antonio Couceiro, Jose, Perez, Amparo, Isabel Piqueras, Ana, Breton, Rafael, Segarra, Inmaculada, Gavilan, Cesar, Jareno, Enrique, Montesinos, Elena, Dapena, Marta, Alvarez, Cristina, Gloria Andres, Ana, Marugan, Victor, Ochoa, Carlos, Alfayate, Santiago, Isabel Menasalvas, Ana, de Miguel, Elisa, Naver, Lars, Soeria-Atmadja, Sandra, Hagas, Vendela, Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I, Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, Martinez B., Marzolini, C., Metzner, K. J., Mueller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch, Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Lecompte, Thanh M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. A., Yerly, S., Wannarit, Pornpun, Techakunakorn, Pornchai, Hansudewechakul, Rawiwan, Wanchaitanawong, Vanichaya, Theansavettrakul, Sookchai, Nanta, Sirisak, Ngampiyaskul, Chaiwat, Phanomcheong, Siriluk, Hongsiriwon, Suchat, Karnchanamayul, Warit, Kwanchaipanich, Ratchanee, Kanjanavanit, Suparat, Kamonpakorn, Nareerat, Nantarukchaikul, Maneeratn, Layangool, Prapaisri, Mekmullica, Jutarat, Lucksanapisitkul, Paiboon, Watanayothin, Sudarat, Lertpienthum, Narong, Warachit, Boonyarat, Hanpinitsak, Sansanee, Potchalongsin, Sathit, Thanasiri, Pimpraphai, Krikajornkitti, Sawitree, Attavinijtrakarn, Pornsawan, Srirojana, Sakulrat, Bunjongpak, Suthunya, Puangsombat, Achara, Na-Rajsima, Sathaporn, Ananpatharachai, Pornchai, Akarathum, Noppadon, Lawtongkum, Weerasak, An, Prapawan Kheunj, Suriyaboon, Thitiporn, Saipanya, Airada, Than-in-at, Kanchana, Jaisieng, Nirattiya, Suaysod, Rapeepan, Chailoet, Sanuphong, Naratee, Naritsara, Kawilapat, Suttipong, Lyall, Hermione, Bamford, Alasdair, Butler, Karim, Doherty, Conor, Foster, Caroline, Francis, Kate, Harrison, Ian, Kenny, Julia, Klein, Nigel, Letting, Gillian, McMaster, Paddy, Murau, Fungai, Nsangi, Edith, Peters, Helen, Prime, Katia, Riordan, Andrew, Shackley, Fiona, Shingadia, Delane, Storey, Sharon, Tudor-Williams, Gareth, Turkova, Anna, Welch, Steve, Collins, Intira Jeannie, Cook, Claire, Dobson, Donna, Fairbrother, Keith, Harper, Lynda, Le Prevost, Marthe, Van Looy, Nadine, Butler, K., Walsh, A., Thrasyvoulou, L., Welch, S., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Sloper, K., Fidler, K., Hague, R., Price, V, Clapson, M., Flynn, J., Abou-Rayyah, A. Cardoso M., Klein, N., Shingadia, D., Gurtin, D., Yeadon, S., Segal, S., Ball, C., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Clough, S., Anguvaa, L., Conway, S., Flood, T., Pickering, A., Murphy, P. McMaster C., Daniels, J., Lees, Y., Thompson, F., Williams, B., Pope, S., Cliffe, L., Smyth, A., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Clarke, D. Rogahn L., Jones, L., Offerman, B., Greenberg, M., Benson, C., Riordan, A., Ibberson, L., Shackley, F., Faust, S. N., Hancock, J., Doerholt, K., Prime, K., Sharland, M., Storey, S., Lyall, H., Monrose, C., Seery, P., Tudor-Williams, G., Menson, E., Callaghan, A., Bridgwood, A., McMaster, P., Evans, J., Blake, E., Yannoulias, A., European Pregnancy Paediat HIV Coh, Microbes in Health and Disease (MHD), Fundación Investigación y Educación en Sida, Instituto de Salud Carlos III, European Commission, Fundación Mutua Madrileña, Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University [Cambridge]-Chiang Mai University (CMU), Pediatrics, and Virology

Subjects
0301 basic medicine, Male, Pediatrics, puberty, [SDV]Life Sciences [q-bio], humanos, Human immunodeficiency virus (HIV), adolescente, LETTONIE, CHILDREN, HIV Infections, medicine.disease_cause, GRECE, desarrollo del niño, Cohort Studies, 0302 clinical medicine, Child Development, CHILD_DEVELOPMENT, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, ADOLESCENTS, Immunology and Allergy, Pooled data, 030212 general & internal medicine, SUEDE, Child, estudios de cohortes, ESPAGNE, 11 Medical and Health Sciences, Anthropometry, THAILANDE, Europe, growth, height, HIV, perinatal, Thailand, Adolescent, Anti-Retroviral Agents, Child, Preschool, Female, Humans, Infant, Puberty, virus diseases, Growth spurt, PAYS BAS, 3. Good health, 17 Psychology and Cognitive Sciences, AIDS, antirretrovirales, Infectious Diseases, POLOGNE, BELGIQUE, Life Sciences & Biomedicine, medicine.medical_specialty, Pediatric hiv, Epidemiology and Social, ROYAUME UNI, Immunology, MASS, European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Virology, medicine, pubertad, Preschool, lactante, ROUMANIE, Science & Technology, business.industry, 06 Biological Sciences, VELOCITY, SUISSE, Regimen, 030104 developmental biology, VIRAL LOAD, antropometría, infecciones por VIH, BODY_HEIGHT, business, IRLANDE, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group., [Objective]: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. [Design]: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. [Methods]: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1–10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. [Results]: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and −1.2 (IQR: −2.3 to −0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20–0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21–1.78) years later in those starting with HAZ less than −3 compared with HAZ at least −1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than −1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least −1, there was no association with age. Girls and boys who initiated ART with HAZ at least −1 maintained a similar height to the WHO reference mean. [Conclusion]: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least −1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age., This work has been partially funded by the Fundación para la Investigación y Prevención de SIDA en España (FIPSE) (FIPSE 3608229/09, FIPSE 240800/09, FIPSE 361910/10), Red Temática de Investigación en SIDA (RED RIS) supported by Instituto de Salud Carlos III (ISCIII) (RD12/0017/0035 and RD12/0017/0037), project as part of the Plan R+D+I and cofinanced by ISCIII- Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER),Mutua Madrileña 2012/0077, Gilead Fellowship 2013/0071, FIS PI15/00694,CoRISpe (RED RIS RD06/0006/0035 y RD06/0006/0021).

Published
2019
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2. Effectiveness of Transmitted Drug Resistance Testing Before Initiation of Antiretroviral Therapy in HIV-Positive Individuals

Author

Lodi, Sara, Günthard, Huldrych F, Gill, John, Phillips, Andrew N, Dunn, David, Vu, Quang, Siemieniuk, Reed, Garcia, Federico, Logan, Roger, Jose, Sophie, Bucher, Heiner C, Scherrer, Alexandra U, et al, Lodi, Sara, Günthard, Huldrych F, Gill, John, Phillips, Andrew N, Dunn, David, Vu, Quang, Siemieniuk, Reed, Garcia, Federico, Logan, Roger, Jose, Sophie, Bucher, Heiner C, Scherrer, Alexandra U, and et al

Abstract

BACKGROUND For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated. METHODS We included individuals from the HIV-CAUSAL Collaboration who enrolled <6 months of HIV diagnosis between 2006 and 2015, were ART-naive, and had measured CD4 count and HIV-RNA. Follow-up started at the date when all inclusion criteria were first met (baseline). We compared 2 strategies: (1) TDR testing within 3 months of baseline versus (2) no TDR testing. We used inverse probability weighting to estimate the 5-year proportion and hazard ratios (HRs) of virological suppression (confirmed HIV-RNA <50 copies/mL), and of AIDS or death under both strategies. RESULTS Of 25,672 eligible individuals (82% males, 52% diagnosed in 2010 or later), 17,189 (67%) were tested for TDR within 3 months of baseline. Of these, 6% had intermediate- or high-level TDR to any antiretroviral drug. The estimated 5-year proportion virologically suppressed was 77% under TDR testing and 74% under no TDR testing; HR 1.06 (95% confidence interval: 1.03 to 1.19). The estimated 5-year risk of AIDS or death was 6% under both strategies; HR 1.03 (95% confidence interval: 0.95 to 1.12). CONCLUSIONS TDR prevalence was low. Although TDR testing improved virological response, we found no evidence that it reduced the incidence of AIDS or death in first 5 years after diagnosis.

Published
2019

3. HIV-1 drug resistance among Ugandan adults attending an urban out-patient clinic

Author

von Braun, Amrei, Sekaggya-Wiltshire, Christine, Bachmann, Nadine, Ssemwanga, Deogratius, Scherrer, Alexandra U, Nanyonjo, Maria, Kapaata, Anne, Kaleebu, Pontiano, Günthard, Huldrych F, Castelnuovo, Barbara, Fehr, Jan, Kambugu, Andrew, von Braun, Amrei, Sekaggya-Wiltshire, Christine, Bachmann, Nadine, Ssemwanga, Deogratius, Scherrer, Alexandra U, Nanyonjo, Maria, Kapaata, Anne, Kaleebu, Pontiano, Günthard, Huldrych F, Castelnuovo, Barbara, Fehr, Jan, and Kambugu, Andrew

Abstract

BACKGROUND Little is known about prevalence of drug resistance among HIV-infected Ugandans, a setting with over 15 years of public-sector access to antiretroviral therapy (ART) and where virological monitoring was only recently introduced. SETTING This study was conducted in the adults' out-patient clinic of the Infectious Diseases Institute, Kampala, Uganda. METHODS HIV genotyping was performed in ART naïve patients and in treatment experienced patients on ART for ≥ six months with virological failure (≥1000 copies/mL). RESULTS A total of 152 ART naïve and 2511 ART experienced patients were included. Transmitted drug resistance was detected in 9 (5.9%) patients. After a median time on ART of 4.7 years (interquartile range (IQR): 2.5-8.7), 190 patients (7.6%) had virological failure with a median viral load of 4.4 log10 copies/mL (IQR:3.9-4.9). Additionally, 146 patients had a viral load between 51 and 999 copies/ml. Most patients with virological failure (142, 74.7%) were on first-line ART. For 163 (85.8%) ART experienced patients genotype results were available. Relevant drug resistance mutations were observed in 135 (82.8%), of which 103 (63.2%) had resistance to two drug classes, and 11 (6.7%) had resistance to all drug classes available in Uganda. CONCLUSION The prevalence of transmitted drug resistance was lower than recently reported by the WHO. With 92% of all patients virologically suppressed on ART, the prevalence of virological failure was low when a cut-off of 1000 copies/mL is applied, and is in-line with the third of the 90-90-90 UNAIDS targets. However, most failing patients had developed multi-class drug resistance.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Published
2018

4. Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance

Author

Lodi, Sara, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Dunn, David, Garcia, Federico, Logan, Roger, Jose, Sophie, Bucher, Heiner C, Scherrer, Alexandra U, Schneider, Marie-Paule, Egger, Matthias, Glass, Tracy R, Reiss, Peter, van Sighem, Ard, Boender, T Sonia, Phillips, Andrew N, Porter, Kholoud, Hawkins, David, Moreno, Santiago, Monge, Susana, Paraskevis, Dimitrios, Simeon, Metallidis, Vourli, Georgia, Sabin, Caroline; https://orcid.org/0000-0001-5173-2760, Hernán, Miguel A, HIV-CAUSAL Collaboration*, Lodi, Sara, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Dunn, David, Garcia, Federico, Logan, Roger, Jose, Sophie, Bucher, Heiner C, Scherrer, Alexandra U, Schneider, Marie-Paule, Egger, Matthias, Glass, Tracy R, Reiss, Peter, van Sighem, Ard, Boender, T Sonia, Phillips, Andrew N, Porter, Kholoud, Hawkins, David, Moreno, Santiago, Monge, Susana, Paraskevis, Dimitrios, Simeon, Metallidis, Vourli, Georgia, Sabin, Caroline; https://orcid.org/0000-0001-5173-2760, Hernán, Miguel A, and HIV-CAUSAL Collaboration*

Abstract

OBJECTIVE: We estimated and compared the risk of clinically identified acquired drug resistance under i) immediate initiation (the currently recommended ART initiation strategy), ii) initiation with CD4 < 500, and iii) initiation with CD4 < 350 cells/mm. DESIGN: Cohort study based on routinely collected data from the HIV-CAUSAL Collaboration. METHODS: For each individual, baseline was the earliest time when all eligibility criteria (ART-naïve, AIDS-free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 count, HIV-RNA, AIDS, ART regimen and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics. RESULTS: In 50,981 eligible individuals, 10% had CD4 count>500 at baseline, and 63% initiated ART during follow-up. Of 2,672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% CI) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 < 500, and 2.8% (2.5,3.0) for initiation with CD4 < 350 cells/mm. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7,2.4) and 1.8% (1.7,2.2). CONCLUSIONS: Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.

Published
2018

6. Human papillomavirus antibody response following HAART initiation among MSM

Author

Combes, Jean-Damien, Clifford, Gary M, Egger, Matthias, Cavassini, Matthias, Hirsch, Hans H, Hauser, Christoph, Calmy, Alexandra, Schmid, Patrick, Bernasconi, Enos, Günthard, Huldrych F, Franceschi, Silvia, Waterboer, Tim, Scherrer, Alexandra U, Swiss HIV Cohort Study, Combes, Jean-Damien, Clifford, Gary M, Egger, Matthias, Cavassini, Matthias, Hirsch, Hans H, Hauser, Christoph, Calmy, Alexandra, Schmid, Patrick, Bernasconi, Enos, Günthard, Huldrych F, Franceschi, Silvia, Waterboer, Tim, Scherrer, Alexandra U, and Swiss HIV Cohort Study

Published
2017

7. Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

Author

Shilaih, Mohaned, Marzel, Alex, Braun, Dominique L, Scherrer, Alexandra U, Kovari, Helen, Young, Jim, Calmy, Alexandra, Darling, Katharine, Battegay, Manuel, Hoffmann, Matthias, Bernasconi, Enos, Thurnheer, Maria C, Günthard, Huldrych F, Kouyos, Roger D, Swiss HIV Cohort Study, Shilaih, Mohaned, Marzel, Alex, Braun, Dominique L, Scherrer, Alexandra U, Kovari, Helen, Young, Jim, Calmy, Alexandra, Darling, Katharine, Battegay, Manuel, Hoffmann, Matthias, Bernasconi, Enos, Thurnheer, Maria C, Günthard, Huldrych F, Kouyos, Roger D, and Swiss HIV Cohort Study

Abstract

After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2-1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation.

Published
2017

8. Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients

Author

Metzner, K J, Scherrer, A U, von Wyl, V, Böni, J, Yerly, S, Klimkait, T, Aubert, V, Furrer, Hansjakob; https://orcid.org/0000-0002-1375-3146, Hirsch, Hans H, Vernazza, P L, Cavassini, M, Calmy, A, Bernasconi, E, Weber, R, Gunthard, H F, Metzner, K J, Scherrer, A U, von Wyl, V, Böni, J, Yerly, S, Klimkait, T, Aubert, V, Furrer, Hansjakob; https://orcid.org/0000-0002-1375-3146, Hirsch, Hans H, Vernazza, P L, Cavassini, M, Calmy, A, Bernasconi, E, Weber, R, and Gunthard, H F

Abstract

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

Published
2014

10. Polymorphic Mutations Associated With the Emergence of the Multinucleoside/Tide Resistance Mutations 69 Insertion and Q151M.

Author

Scherrer, Alexandra U., von Wyl, Viktor, Götte, Matthias, Klimkait, Thomas, Cellerai, Cristina, Yerly, Sabine, Böni, Jürg, Held, Leonhard, Ledergerber, Bruno, and Günthard, Huldrych F.

Abstract

We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M.The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR.The 69 insertion and TAM 1were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2.Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations. [ABSTRACT FROM AUTHOR]

Published
2012
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11. Viral Suppression Rates in Salvage Treatment With Raltegravir Improved With the Administration of Genotypic Partially Active or Inactive Nucleoside/Tide Reverse Transcriptase Inhibitors.

Author

Scherrer, Alexandra U, Wyl, Viktor von, Böni, Jürg, Yerly, Sabine, Klimkait, Thomas, Bürgisser, Philippe, Garzoni, Christian, Hirschel, Bernard, Cavassini, Matthias, Battegay, Manuel, Vernazza, Pietro L, Bernasconi, Enos, Ledergerber, Bruno, and Günthard, Huldrych F

Abstract

Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs.The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response.One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively.Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted. [ABSTRACT FROM AUTHOR]

Published
2011
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12. Implementation of Raltegravir in Routine Clinical Practice: Selection Criteria for Choosing This Drug, Virologic Response Rates, and Characteristics of Failures.

Author

Scherrer, Alexandra U., Von Wyl, Viktor, Fux, Christof A., Opravil, Milos, Bucher, Heiner C., Fayet, Aurélie, Decosterd, Laurent A., Hirschel, Bernhard, Khanlari, Bettina, Yerly, Sabine, Klimkait, Thomas, Furrer, Hansjakob, Ledergerber, Bruno, and Günthard, Huldrych F.

Subjects
*ANTIRETROVIRAL agents, *LOGISTIC regression analysis, *CLINICAL trials, *MEDICAL virology, *VIRAL disease treatment
Abstract

The article presents a study on the efficiency of data, virologic suppression rates, and factors for failures of raltegravir (RAL) in a routine clinical care setting. The study uses a logistic regression to analyze the factors, an intent-to-treat analysis for the virologic outcome, and imputation for the response rate. It states that the predominant factor resulted to be a regimen containing enfuvirtide, the overall response rate is 80.9%, and the viral suppression rates are 71.8% and 95.8%.

Published
2010
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13. HIV Transmission Chains Exhibit Greater HLA-B Homogeneity Than Randomly Expected

Author

Huyen Nguyen, Thorball, Christian W., Fellay, Jacques, Boni, Jurg, Yerly, Sabine, Perreau, Matthieu, Klimkait, Thomas, Kusejko, Katharina, Bachmann, Nadine, Chaudron, Sandra E., Paioni, Paolo, Thurnheer, Maria C., Battegay, Manuel, Cavassini, Matthias, Vernazza, Pietro, Bernasconi, Enos, Gunthard, Huldrych F., Kouyos, Roger, Anagnostopoulos, A., Braun, D. L., Bucher, H. C., Calmy, A., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Furrer, H., Fux, C. A., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B. Martinez, Marzolini, C., Metzner, K. J., Mueller, N., Nicca, D., Pantaleo, G., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Trkola, A., Wandeler, G., and Weber, R.

Subjects
concordance, immune control, transmission chains, association, virus diseases, determinants, restriction, t-cell responses, escape mutations, hla, coevolution, evolution, class-i, mate choice
Abstract

Background: HIV's capacity to escape immune recognition by human leukocyte antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to the host HLA type and could better improve therapeutic strategies against HIV., Materials and Methods: Three hundred one to 325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA class I data were compiled at 3 specificity levels: 4-digit, 2-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as 2 measures: the proportion of transmission pairs, which are HLA concordant, and the average percentage of allele matches within all clusters. These measures were compared with the mean value across randomizations with randomly assorted individuals., Results: We repeated the analysis for different HLA classification levels and separately for HLA-A,-B, and-C. Subanalyses by the risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs. 0.251, P value = 0.009; supertype clusters: 0.659 vs. 0.611, P value = 0.002; supertype pairs: 0.655 vs. 0.608, P value = 0.014). Risk group restriction caused the effect to disappear for men-who-have-sexwith- men but not for other risk groups. We also examined if protective HLA alleles B27 and B57 were under-or overrepresented in the transmission chains, although this yielded no significant pattern., Conclusions: The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.

14. Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance

Author

Lodi, Sara, Günthard, Huldrych F, Dunn, David, Garcia, Federico, Logan, Roger, Jose, Sophie, Bucher, Heiner C, Scherrer, Alexandra U, Schneider, Marie-Paule, Egger, Matthias, Glass, Tracy R, Reiss, Peter, Van Sighem, Ard, Boender, T Sonia, Phillips, Andrew N, Porter, Kholoud, Hawkins, David, Moreno, Santiago, Monge, Susana, Paraskevis, Dimitrios, Simeon, Metallidis, Vourli, Georgia, Sabin, Caroline, Hernán, Miguel A, and Collaboration, The HIV-CAUSAL

Subjects
610 Medicine & health, 360 Social problems & social services, 3. Good health
Abstract

OBJECTIVE We estimated and compared the risk of clinically identified acquired drug resistance under i) immediate initiation (the currently recommended ART initiation strategy), ii) initiation with CD4 500 at baseline, and 63% initiated ART during follow-up. Of 2,672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% CI) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4

15. Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals

Author

Calmy, Alexandra, Scherrer, Alexandra U, Günthard, Huldrych F, Thurnheer Zürcher, Maria Christine, Kovari, Helen, Shilaih, Mohaned, Kouyos, Roger D, Battegay, Manuel, Braun, Dominique L, Young, Jim, Marzel, Alex, Bernasconi, Enos, Darling, Katharine, and Hoffmann, Matthias

Subjects
610 Medicine & health, 3. Good health
Abstract

After several years of steady decline, syphilis is reemerging globally as a public health hazard, especially among people living with human immunodeficiency virus (HIV). Syphilis resurgence is observed mainly in men who have sex with men (MSM), yet other transmission groups are affected too. In this manuscript, we study the factors associated with syphilis incidence in the Swiss HIV cohort study in the era of highly effective antiretrovirals. Using parametric interval censored models with fixed and time-varying covariates, we studied the immunological, behavioral, and treatment-related elements associated with syphilis incidence in 3 transmission groups: MSM, heterosexuals, and intravenous drug users. Syphilis incidence has been increasing annually since 2005, with up to 74 incident cases per 1000 person-years in 2013, with MSM being the population with the highest burden (92% of cases). While antiretroviral treatment (ART) in general did not affect syphilis incidence, nevirapine (NVP) was associated with a lower hazard of syphilis incidence (multivariable hazard ratio 0.5, 95% confidence interval 0.2-1.0). We observed that condomless sex and younger age were associated with higher syphilis incidence. Moreover, time-updated CD4, nadir CD4, and CD8 cell counts were not associated with syphilis incidence. Finally, testing frequency higher than the recommended once a year routine testing was associated with a 2-fold higher risk of acquiring syphilis. Condomless sex is the main driver of syphilis resurgence in the Swiss HIV Cohort study; ART and immune reconstitution provide no protection against syphilis. This entails targeted interventions and frequent screening of high-risk populations. There is no known effect of NVP on syphilis; therefore, further clinical, epidemiological, and microbiological investigation is necessary to validate our observation.

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