Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy

Bannister, Wendy; Cozzi‐Lepri, Alessandro; Lazzarin, Adriano; Viard, Jean‐Paul; Beniowski, Marek; Machala, Ladislav; Phillips, Andrew; Losso, M.; Elias, Christelle; Vetter, N; Zangerle, Robert; Karpov, Igor; Vassilenko, Anne; Мицура, В. М.; Суетнов, О. Н.; Clumeck, Nathan; Wit, S. De; Delforge, Marie-Luce; Colebunders, R; Vandekerckhove, Linos; Hadžiosmanović, Vesna; Kostov, Kosta; Begovać, Josip; Rozsypal, Hanuš; Sedláček, Dalibor; Nielsen, Jens; Kronborg, Gitte; Benfield, T; Larsen, M.; Gerstoft, J; Katzenstein, Terese L.; Hansen, BR; Skinhøj, Peter; Pedersen, Court; Oestergaard, Lars; Zilmer, Kai; Šmidt, Jelena; Ristola, Matti; Katlama, Christine; Girard, Pierre Marie; Livrozet, Jean-Michel; Vanhems, Philippe; Pradier, Christian; Dabis, François; Néau, Didier; Rockstroh, Jürgen K.; Schmidt, Robert M.; Lunzen, Jan van; Degen, Olaf; Stellbrink, H. J.; Staszewski, S; Goethe, John W.; Bogner, J. R.; Fätkenheuer, Gerd; Kosmidis, J.; Gargalianos, Panagiotis; Xylomenos, G.; Perdios, J.; Panos, George; Filandras, A.; Karabatsaki, E.; Bánhegyi, Dénes; Mulcahy, Fiona; Yust, Israel; Turner, Dianna; Burke, Michael; Pollack, Shimon; Hassoun, Gamal; Maayan, Shlomo; Chiesi, Antonio; Esposito, Roberto; Mazeu, I.; Mussini, Cristina; Arici, Claudio; Pristerà, Raffaele; Mazzotta, Francesco; Gabbuti, Andrea; Vullo, Vincenzo; Lichtner, Miriam; Chirianni, Antonio; Montesarchio, E.; Gargiulo, Miriam; Antonucci, Giorgio; Iacomi, Fabio; Narciso, Pasquale; Vlassi, Chrysoula; Zaccarelli, Mauro; Finazzi, Renato; Galli, Massimo; Ridolfo, Anna Lisa; Monforte, Antonella d’Arminio; Rozentāle, Baiba; Zeltiņa, Indra; Chaplinskas, Saulius; Hemmer, R; Staub, Thérèse; Reiss, Peter; Bruun, JN; Mæland, A; Ormaasen, Vidar; Knysz, Brygida; Gąsiorowski, Jacek; Horban, Andrzéj; Bąkowska, Elżbieta; Grzeszczuk, Anna; Flisiak, Robert; Boroń-Kaczmarska, Anna; Pynka, M; Mularska, E.; H, Trocha; Jabłonowska, Elżbieta; Małolepsza, Ewa; Wójcik, Kamila; Antúnes, Francisco; Valadas, Emília; Kamal, Mehnaz; Maltêz, Fernando; Duiculescu, Dan; Rakhmanova, Aza; Vinogradova, Elena; Jevtović, Djordje; Mokrás, M; Staneková, Danica; Tomažič, Janez; González-Lahoz, Juan; Soriano, Vincent; Labarga, Pablo; Medrano, José; Moreno, Santiago; Clotet, Bonaventura; Jou, Antoni; Paredes, Roger; Tural, C.; Puig, Javier Juega; Bravo, Isabel; Miró, JM; Domingo, Peré; Gutiérrez, Mar; Mateo, Gràcia; Sambeat, María A.; Karlsson, Anders; Ledergerber, Bruno; Weber, Rainer; Hirschel, Bernard; Boffi, E; Furrer, Hansjakob; Battegay, Manuel; Elzi, Luigia; Кравченко, Е. Н.; Chentsova, N; Servitskiy, S.; Antoniak, Sergii; Краснов, Максим Ігорович; Barton, Simon; Johnson, Anne M; Mercey, D; Johnson, Margaret; Mocroft, Amanda; Murphy, M.; Weber, Jonathan; Scullard, George; Fisher, Martin; Leen, Clifford; Gatell, José M.; Bg, Gazzard; Montforte, Antonella D’Arminio; Lundgren, Jens D; Kirk, Ole; Friis-Møller, Nina; Ellefson, Mark; Borch, Anders; Podlekareva, D; Kjær, Jesper; Peters, Lars; Reekie, J.; Kowalska, Justyna D.

doi:10.1093/jac/dkr006

Cited by 15 publications

(8 citation statements)

References 26 publications

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“…Other studies have examined predictors of resistance [8-10,21-23] and failure [24,25] in seroprevalent cohorts. Our finding that higher CD4 count at cART initiation was an independent predictor of risk of failure and drug resistance was supported by two of these studies [9,10,24].…”

Section: Discussionmentioning

confidence: 99%

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

Lodi

Phillips

Fidler³

et al. 2013

PLoS ONE

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BackgroundThe development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation.MethodsPatients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion).ResultsOf 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively.ConclusionAlthough the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.

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Section: Discussionmentioning

confidence: 99%

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

Lodi

Phillips

Fidler³

et al. 2013

PLoS ONE

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“…No more new cases of MDR does not mean that resistance will disappear completely, as can be seen by several drugs that are still showing a high prevalence of resistance in 2012. 13 Resistance to the newest agents can emerge, resulting in the appearance of novel drug resistance mutations in the HIV-1 polymerase, integrase and envelope genes. 5 Moreover, as a consequence of ongoing transmission of drug resistance, newly infected patients may already have drug-resistant virus.…”

Section: Discussionmentioning

confidence: 99%

The demise of multidrug-resistant HIV-1: the national time trend in Portugal

Vercauteren

Theys

Carvalho³

et al. 2012

Journal of Antimicrobial Chemotherapy

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ObjectivesDespite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal.Patients and methodsWe used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR.ResultsWe observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7–8.4) in 2001–03, 6.0% (95% CI: 4.9–7.2) in 2003–05, 3.7% (95% CI: 2.8–4.8) in 2005–07 and 1.6% (95% CI: 1.1–2.2) in 2007–09 down to 0.6% (95% CI: 0.3–0.9) in 2009–12 [OR = 0.80 (95% CI: 0.75–0.86); P < 0.001]. In July 2011 the last new case of MDR was seen.ConclusionsThe prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.

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“…Nevertheless, the proportion of individuals with HIV RNA replication suppressed to ,50 copies/mL has increased continuously over the past decade [5,6]. Whether the emergence of HIV-1 drug resistance has been reduced by the same extent is uncertain and difficult to assess [7,8]. Incidence studies based on genotypic drug resistance test (GRT) data from clinical practice often struggle with limitations, namely, that patients subjected to GRTs may not be representative for all potentially eligible individuals or the whole population of HIV-infected, treated individuals [3,9].…”

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confidence: 99%

Incidence of HIV-1 Drug Resistance Among Antiretroviral Treatment–Naive Individuals Starting Modern Therapy Combinations

Wyl

Yerly

Böni

et al. 2011

Clinical Infectious Diseases

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Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy

Cited by 15 publications

References 26 publications

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

The demise of multidrug-resistant HIV-1: the national time trend in Portugal

Incidence of HIV-1 Drug Resistance Among Antiretroviral Treatment–Naive Individuals Starting Modern Therapy Combinations

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