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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2012

Open Access 01-12-2012 | Research article

Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study

Authors: Mattia CF Prosperi, Massimiliano Fabbiani, Iuri Fanti, Mauro Zaccarelli, Manuela Colafigli, Annalisa Mondi, Alessandro D’Avino, Alberto Borghetti, Roberto Cauda, Simona Di Giambenedetto

Published in: BMC Infectious Diseases | Issue 1/2012

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Abstract

Background

Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years.

Methods

Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients’ markers.

Results

1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events.

Conclusions

After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen.
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Literature
1.
Palella FJ, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, Holmberg SD, HIV Outpatient Study Investigators: Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006, 43: 27-34. 10.1097/01.qai.0000233310.90484.16.CrossRefPubMed
2.
Vo TT, Ledergerber B, Keiser O, Hirschel B, Furrer H, Battegay M, Cavassini M, Bernasconi E, Vernazza P, Weber R, Swiss HIV Cohort Study: Durability and outcome of initial antiretroviral treatments received during 2000–2005 by patients in the Swiss HIV Cohort Study. J Infect Dis. 2008, 197: 1685-1694. 10.1086/588141.CrossRefPubMed
3.
Elzi L, Marzolini C, Furrer H, Ledergerber B, Cavassini M, Hirschel B, Vernazza P, Bernasconi E, Weber R, Battegay M, Swiss HIV Cohort Study: Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008. Arch Intern Med. 2010, 170: 57-65. 10.1001/archinternmed.2009.432.CrossRefPubMed
4.
Strategies for Management of Anti-Retroviral Therapy/INSIGHT; DAD Study Groups: Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS. 2008, 22: F17-F24.CrossRef
5.
Ciccarelli N, Fabbiani M, Di Giambenedetto S, Fanti I, Baldonero E, Bracciale L, Tamburrini E, Cauda R, De Luca A, Silveri MC: Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients. Neurology. 2011, 76: 1403-1409. 10.1212/WNL.0b013e31821670fb.CrossRefPubMed
6.
Fabbiani M, Bracciale L, Doino M, D'Avino A, Marzocchetti A, Navarra P, Cauda R, De Luca A, Di Giambenedetto S: Tenofovir discontinuation could predispose to urolithiasis in atazanavir-treated patients. J Infect. 2011, 62: 319-321. 10.1016/j.jinf.2011.02.004.CrossRefPubMed
7.
Islam F, Wu J, Jansson J, Wilson D: Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012, 10.1111/j.1468-1293.2012.00996.x. in press
8.
O'Brien ME, Clark RA, Besch CL, Myers L, Kissinger P: Patterns and correlates of discontinuation of the initial HAART regimen in an urban outpatient cohort. J Acquir Immune Defic Syndr. 2003, 34: 407-414. 10.1097/00126334-200312010-00008.CrossRefPubMed
9.
Mocroft A, Phillips AN, Soriano V, Rockstroh J, Blaxhult A, Katlama C, Boron-Kaczmarska A, Viksna L, Kirk O, Lundgren JD, EuroSIDA Study Group: Reasons for stopping antiretrovirals used in an initial highly active antiretroviral regimen: increased incidence of stopping due to toxicity or patient/physician choice in patients with hepatitis C coinfection. AIDS Res Hum Retroviruses. 2005, 21: 743-752. 10.1089/aid.2005.21.743.CrossRefPubMed
10.
Yuan Y, L'italien G, Mukherjee J, Iloeje UH: Determinants of discontinuation of initial highly active antiretroviral therapy regimens in a US HIV-infected patient cohort. HIV Med. 2006, 7: 156-162. 10.1111/j.1468-1293.2006.00355.x.CrossRefPubMed
11.
d'Arminio Monforte A, Lepri AC, Rezza G, Pezzotti P, Antinori A, Phillips AN, Angarano G, Colangeli V, De Luca A, Ippolito G, Caggese L, Soscia F, Filice G, Gritti F, Narciso P, Tirelli U, Moroni M: Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. AIDS. 2000, 14: 499-507. 10.1097/00002030-200003310-00005.CrossRefPubMed
12.
Lubomirov R, Colombo S, di Iulio J, Ledergerber B, Martinez R, Cavassini M, Hirschel B, Bernasconi E, Elzi L, Vernazza P, Furrer H, Günthard HF, Telenti A, Swiss HIV Cohort Study: Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study. J Infect Dis. 2011, 203: 246-257. 10.1093/infdis/jiq043.CrossRefPubMedPubMedCentral
13.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002, 106: 3143-3421.
14.
15.
Torti C, Lapadula G, Casari S, Puoti M, Nelson M, Quiros-Roldan E, Bella D, Pastore G, Ladisa N, Minoli L, Sotgiu G, Mazzotta F, Lo Caputo S, Di Perri G, Filice G, Tinelli C, Carosi G, EPOKA-MASTER Study Group: Incidence and risk factors for liver enzyme elevation during highly active antiretroviral therapy in HIV-HCV co-infected patients: results from the Italian EPOKA-MASTER Cohort. BMC Infect Dis. 2005, 5: 58-10.1186/1471-2334-5-58.CrossRefPubMedPubMedCentral
16.
Reekie J, Reiss P, Ledergerber B, Sedlacek D, Parczewski M, Gatell J, Katlama C, Fätkenheuer G, Lundgren JD, Mocroft A, EuroSIDA study group: A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study. HIV Med. 2011, 12 (5): 259-68. 10.1111/j.1468-1293.2010.00877.x.CrossRefPubMed
17.
18.
Gazzard B, Balkin A, Hill A: Analysis of neuropsychiatric adverse events during clinical trials of efavirenz in antiretroviral-naive patients: a systematic review. AIDS Rev. 2010, 12: 67-75.PubMed
19.
Scourfield A, Zheng J, Chinthapalli S, Waters L, Martin T, Mandalia S, Nelson M: Discontinuation of Atripla® as first-line therapy in HIV-1 infected individuals. AIDS. 2012, in press
20.
Airoldi M, Zaccarelli M, Bisi L, Bini T, Antinori A, Mussini C, Bai F, Orofino G, Sighinolfi L, Gori A, Suter F, Maggiolo F: One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects. Patient Prefer Adherence. 2010, 4: 115-125.PubMedPubMedCentral
21.
Floridia M, Giuliano M, Palmisano L, Vella S: Gender differences in the treatment of HIV infection. Pharmacol Res. 2008, 58: 173-182. 10.1016/j.phrs.2008.07.007.CrossRefPubMed
22.
Ofotokun I, Chuck SK, Hitti JE: Antiretroviral pharmacokinetic profile: a review of sex differences. Gend Med. 2007, 4: 106-119. 10.1016/S1550-8579(07)80025-8.CrossRefPubMed
23.
Robison LS, Westfall AO, Mugavero MJ, Kempf MC, Cole SR, Allison JJ, Willig JH, Raper JL, Wilcox CM, Saag MS: Short-term discontinuation of HAART regimens more common in vulnerable patient populations. AIDS Res Hum Retroviruses. 2008, 24: 1347-1355. 10.1089/aid.2008.0083.CrossRefPubMedPubMedCentral
24.
Aulicino PC, Bello G, Rocco C, Romero H, Mangano A, Morgado MG, Sen L: Description of the first full-length HIV type 1 subtype F1 strain in Argentina: implications for the origin and dispersion of this subtype in South America. AIDS Res Hum Retroviruses. 2007, 23: 1176-1182. 10.1089/aid.2007.0038.CrossRefPubMed
25.
Teixeira SLM, Guimaraes ML, Leite T, Coelho A, Campos DP, Veloso V, Morgado MG: Disease progression in a cohort of HIV-1 positive patients from Rio de Janeiro, Brazil: potential role of HIV-1 subtypes and HLA-B alleles. 2011, Rome: 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Abstract n CDA105
26.
27.
Braithwaite RS, Kozal MJ, Chang CC, Roberts MS, Fultz SL, Goetz MB, Gibert C, Rodriguez-Barradas M, Mole L, Justice AC: Adherence, virological and immunological outcomes for HIV-infected veterans starting combination antiretroviral therapies. AIDS. 2007, 21: 1579-1589. 10.1097/QAD.0b013e3281532b31.CrossRefPubMedPubMedCentral
28.
Rekić D, Clewe O, Röshammar D, Flamholc L, Sönnerborg A, Ormaasen V, Gisslén M, Abelö A, Ashton M: Bilirubin-a potential marker of drug exposure in atazanavir-based antiretroviral therapy. AAPS J. 2011, 13: 598-605. 10.1208/s12248-011-9299-0.CrossRefPubMedPubMedCentral
29.
Lampe FC, Gatell JM, Staszewski S, Johnson MA, Pradier C, Gill MJ, de Lazzari E, Dauer B, Youle M, Fontas E, Krentz HB, Phillips AN: Changes over time in risk of initial virologic failure of combination antiretroviral therapy: a multicohort analysis, 1996 to 2002. Arch Intern Med. 2006, 166: 521-528. 10.1001/archinte.166.5.521.CrossRefPubMed
30.
Lampe FC, Smith CJ, Madge S, Kinloch-de Loes S, Tyrer M, Sabin CA, Chaloner C, Youle M, Johnson MA, Phillips AN: Success of clinical care for human immunodeficiency virus infection according to demographic group among sexually infected patients in a routine clinic population, 1999 to 2004. Arch Intern Med. 2007, 167: 692-700. 10.1001/archinte.167.7.692.CrossRefPubMed
31.
Prosperi MC, Cozzi-Lepri A, Antinori A, Cassola G, Torti C, Ursitti MA, Pellizzer GP, Giacometti A, d'Arminio Monforte A, De Luca A, Icona Foundation Study Group: Favourable evolution of virologic and immunological profiles in treated and untreated patients in Italy in the period 1998–2008. HIV Med. 2011, 12: 174-182. 10.1111/j.1468-1293.2010.00866.x.CrossRefPubMed
32.
Deeks SG, Gange SJ, Kitahata MM, Saag MS, Justice AC, Hogg RS, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Benson CA, Collier AC, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Kushel MB, Goedert JJ, McKaig RG, Moore RD: Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America. Clin Infect Dis. 2009, 49: 1582-1590. 10.1086/644768.CrossRefPubMedPubMedCentral
33.
Di Giambenedetto S, Prosperi M, Fanti I, Bruzzone B, Paolucci S, Penco G, Meini G, Di Biagio A, Paolini E, Micheli V, Meraviglia P, Castelli P, Corsi P, Gonnelli A, Fabbiani M, Zazzi M, De Luca A, ARCA Collaborative Group: Update on emergence of HIV-1 resistance to antiretroviral drug classes in an Italian national database: 2007–2009. Clin Microbiol Infect. 2011, 17: 1352-1355.CrossRefPubMed
34.
Bannister WP, Cozzi-Lepri A, Kjær J, Clotet B, Lazzarin A, Viard JP, Kronborg G, Duiculescu D, Beniowski M, Machala L, Phillips A, EuroSIDA group: Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy. J Antimicrob Chemother. 2011, 66: 901-911. 10.1093/jac/dkr006.CrossRefPubMed
35.
Prosperi MC, Mackie N, Di Giambenedetto S, Zazzi M, Camacho R, Fanti I, Torti C, Sönnerborg A, Kaiser R, Codoñer FM, Van Laethem K, Bansi L, van de Vijver DA, Geretti AM, De Luca A, SEHERE consortium: Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study. J Antimicrob Chemother. 2011, 66: 1886-1896. 10.1093/jac/dkr171.CrossRefPubMed
36.
Bracciale L, Colafigli M, Zazzi M, Corsi P, Meraviglia P, Micheli V, Maserati R, Gianotti N, Penco G, Setti M, Di Giambenedetto S, Butini L, Vivarelli A, Trezzi M, De Luca A: Prevalence of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy: evolution over 12 years and predictors. J Antimicrob Chemother. 2009, 64: 607-615. 10.1093/jac/dkp246.CrossRefPubMed
37.
Di Giambenedetto S, Bracciale L, Colafigli M, Cattani P, Pinnetti C, Bacarelli A, Prosperi M, Fadda G, Cauda R, De Luca A: Declining prevalence of HIV-1 drug resistance in treatment-failing patients: a clinical cohort study. Antivir Ther. 2007, 12: 835-839.PubMed
38.
Di Giambenedetto S, Zazzi M, Corsi P, Gonnelli A, Di Pietro M, Giacometti A, Almi P, Trezzi M, Boeri E, Gianotti N, Menzo S, Del Gobbo R, Francisci D, Nerli A, Galli L, De Luca A, Antiretroviral Resistance Cohort Analysis Study Group: Evolution and predictors of HIV type-1 drug resistance in patients failing combination antiretroviral therapy in Italy. Antivir Ther. 2009, 14: 359-369.PubMed
39.
May MT, Sterne JA, Costagliola D, Sabin CA, Phillips AN, Justice AC, Dabis F, Gill J, Lundgren J, Hogg RS, de Wolf F, Fätkenheuer G, Staszewski S, d'Arminio Monforte A, Egger M, Antiretroviral Therapy (ART) Cohort Collaboration: HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis. Lancet. 2006, 368: 451-458.CrossRefPubMed
40.
Cicconi P, Cozzi-Lepri A, Castagna A, Trecarichi EM, Antinori A, Gatti F, Cassola G, Sighinolfi L, Castelli P, d'Arminio Monforte A, ICoNA Foundation Study Group: Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients. HIV Med. 2010, 11: 104-113. 10.1111/j.1468-1293.2009.00750.x.CrossRefPubMed
41.
Prosperi MC, Altmann A, Rosen-Zvi M, Aharoni E, Borgulya G, Bazso F, Sönnerborg A, Schülter E, Struck D, Ulivi G, Vandamme AM, Vercauteren J, Zazzi M, EuResist and Virolab study groups: Investigation of expert rule bases, logistic regression, and non-linear machine learning techniques for predicting response to antiretroviral treatment. Antivir Ther. 2009, 14: 433-442.PubMed
42.
Prosperi MC, Di Giambenedetto S, Fanti I, Meini G, Bruzzone B, Callegaro A, Penco G, Bagnarelli P, Micheli V, Paolini E, Di Biagio A, Ghisetti V, Di Pietro M, Zazzi M, De Luca A, ARCA cohort: A prognostic model for estimating the time to virologic failure in HIV-1 infected patients undergoing a new combination antiretroviral therapy regimen. BMC Med Inform Decis Mak. 2011, 11: 40-10.1186/1472-6947-11-40.CrossRefPubMedPubMedCentral
43.
Larder BA, Revell A, Mican JM, Agan BK, Harris M, Torti C, Izzo I, Metcalf JA, Rivera-Goba M, Marconi VC, Wang D, Coe D, Gazzard B, Montaner J, Lane HC: Clinical evaluation of the potential utility of computational modeling as an HIV treatment selection tool by physicians with considerable HIV experience. AIDS Patient Care STDS. 2011, 25: 29-36. 10.1089/apc.2010.0254.CrossRefPubMedPubMedCentral
44.
Robbins GK, Johnson KL, Chang Y, Jackson KE, Sax PE, Meigs JB, Freedberg KA: Predicting virologic failure in an HIV clinic. Clin Infect Dis. 2010, 50: 779-786.PubMedPubMedCentral
Metadata
Title
Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study
Authors
Mattia CF Prosperi
Massimiliano Fabbiani
Iuri Fanti
Mauro Zaccarelli
Manuela Colafigli
Annalisa Mondi
Alessandro D’Avino
Alberto Borghetti
Roberto Cauda
Simona Di Giambenedetto
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2012
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-12-296

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