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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients

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

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Efavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption.

Methods

Patients starting any cART regimen including EFV + 2NRTIs or switching to EFV + 2NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model.

Results

Overall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, p < 0.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, p = 0.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, p = 0.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk.

Conclusions

In our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.
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Literature
1.
go back to reference Cooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, Clumeck N, Walmsley S, Ting N, Coakley E, Reeves JD, Reyes-Teran G, Westby M, Van Der Ryst E, Ive P, Mohapi L, Mingrone H, Horban A, Hackman F, Sullivan J, Mayer H: Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010, 201: 803-813. 10.1086/650697.CrossRefPubMed Cooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, Clumeck N, Walmsley S, Ting N, Coakley E, Reeves JD, Reyes-Teran G, Westby M, Van Der Ryst E, Ive P, Mohapi L, Mingrone H, Horban A, Hackman F, Sullivan J, Mayer H: Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010, 201: 803-813. 10.1086/650697.CrossRefPubMed
2.
go back to reference Rockstroh JK, Lennox JL, Dejesus E, Saag MS, Lazzarin A, Wan H, Walker ML, Xu X, Zhao J, Teppler H, Dinubile MJ, Rodgers AJ, Nguyen BY, Leavitt R, Sklar P: STARTMRK Investigators. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis. 2011, 53: 807-816. 10.1093/cid/cir510.CrossRefPubMed Rockstroh JK, Lennox JL, Dejesus E, Saag MS, Lazzarin A, Wan H, Walker ML, Xu X, Zhao J, Teppler H, Dinubile MJ, Rodgers AJ, Nguyen BY, Leavitt R, Sklar P: STARTMRK Investigators. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis. 2011, 53: 807-816. 10.1093/cid/cir510.CrossRefPubMed
3.
go back to reference Vieira MC, Kumar RN, Jansen JP: Comparative effectiveness of efavirenz, protease inhibitors, and raltegravir-based regimens as first-line treatment for HIV-infected adults: a mixed treatment comparison. HIV Clin Trials. 2011, 12: 175-189. 10.1310/HCT1204-175.CrossRefPubMed Vieira MC, Kumar RN, Jansen JP: Comparative effectiveness of efavirenz, protease inhibitors, and raltegravir-based regimens as first-line treatment for HIV-infected adults: a mixed treatment comparison. HIV Clin Trials. 2011, 12: 175-189. 10.1310/HCT1204-175.CrossRefPubMed
4.
go back to reference Andersson LM, Vesterbacka J, Blaxhult A, Flamholc L, Nilsson S, Ormaasen V, Sönnerborg A, Gisslén M: Lopinavir/ritonavir, atazanavir/ritonavir, and efavirenz in antiretroviral-naïve HIV-1-infected individuals over 144 weeks: An open-label randomized controlled trial. Scand J Infect Dis. 2013, 45: 543-551. 10.3109/00365548.2012.756985.CrossRefPubMed Andersson LM, Vesterbacka J, Blaxhult A, Flamholc L, Nilsson S, Ormaasen V, Sönnerborg A, Gisslén M: Lopinavir/ritonavir, atazanavir/ritonavir, and efavirenz in antiretroviral-naïve HIV-1-infected individuals over 144 weeks: An open-label randomized controlled trial. Scand J Infect Dis. 2013, 45: 543-551. 10.3109/00365548.2012.756985.CrossRefPubMed
7.
go back to reference Williams I, Churchill D, Anderson J, Boffito M, Bower M, Cairns G, Cwynarski K, Edwards S, Fidler S, Fisher M, Freedman A, Geretti AM, Gilleece Y, Horne R, Johnson M, Khoo S, Leen C, Marshall N, Nelson M, Orkin C, Paton N, Phillips A, Post F, Pozniak A, Sabin C, Trevelion R, Ustianowski A, Walsh J, Waters L, Wilkins E, Winston A, Youle M: British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Med. 2012, 13 (Suppl 2): 1-85. Williams I, Churchill D, Anderson J, Boffito M, Bower M, Cairns G, Cwynarski K, Edwards S, Fidler S, Fisher M, Freedman A, Geretti AM, Gilleece Y, Horne R, Johnson M, Khoo S, Leen C, Marshall N, Nelson M, Orkin C, Paton N, Phillips A, Post F, Pozniak A, Sabin C, Trevelion R, Ustianowski A, Walsh J, Waters L, Wilkins E, Winston A, Youle M: British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Med. 2012, 13 (Suppl 2): 1-85.
9.
go back to reference Rihs TA, Begley K, Smith DE, Sarangapany J, Callaghan A, Kelly M, Post JJ, Gold J: Efavirenz and chronic neuropsychiatric symptoms: a cross-sectional case control study. HIV Med. 2006, 7: 544-548. 10.1111/j.1468-1293.2006.00419.x.CrossRefPubMed Rihs TA, Begley K, Smith DE, Sarangapany J, Callaghan A, Kelly M, Post JJ, Gold J: Efavirenz and chronic neuropsychiatric symptoms: a cross-sectional case control study. HIV Med. 2006, 7: 544-548. 10.1111/j.1468-1293.2006.00419.x.CrossRefPubMed
10.
go back to reference Prosperi MC, Fabbiani M, Fanti I, Zaccarelli M, Colafigli M, Mondi A, D’Avino A, Borghetti A, Cauda R, Di Giambenedetto S: Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study. BMC Infect Dis. 2012, 12: 296-10.1186/1471-2334-12-296.CrossRefPubMedPubMedCentral Prosperi MC, Fabbiani M, Fanti I, Zaccarelli M, Colafigli M, Mondi A, D’Avino A, Borghetti A, Cauda R, Di Giambenedetto S: Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study. BMC Infect Dis. 2012, 12: 296-10.1186/1471-2334-12-296.CrossRefPubMedPubMedCentral
11.
go back to reference 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 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
14.
go back to reference Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M: Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era. Patient Prefer Adherence. 2012, 6: 427-433.CrossRefPubMedPubMedCentral Sterrantino G, Santoro L, Bartolozzi D, Trotta M, Zaccarelli M: Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era. Patient Prefer Adherence. 2012, 6: 427-433.CrossRefPubMedPubMedCentral
17.
go back to reference Scourfield A, Zheng J, Chinthapalli S, Waters L, Martin T, Mandalia S, Nelson M, et al: Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals. AIDS. 2012, 26: 1399-1401. 10.1097/QAD.0b013e328353b047.CrossRefPubMed Scourfield A, Zheng J, Chinthapalli S, Waters L, Martin T, Mandalia S, Nelson M, et al: Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals. AIDS. 2012, 26: 1399-1401. 10.1097/QAD.0b013e328353b047.CrossRefPubMed
18.
go back to reference Zaccarelli M, Soldani F, Liuzzi G, et al: Presented at: 9th Conference on Retroviruses and Opportunistic Infections. CNS Side Effects as Main Risk Factor for Efavirenz Failure and Transient HIV-RNA Elevation (Abstract N 720-T). 2002, Seattle, WA, USA Zaccarelli M, Soldani F, Liuzzi G, et al: Presented at: 9th Conference on Retroviruses and Opportunistic Infections. CNS Side Effects as Main Risk Factor for Efavirenz Failure and Transient HIV-RNA Elevation (Abstract N 720-T). 2002, Seattle, WA, USA
19.
go back to reference Bangsberg DR, Ragland K, Monk A, Deeks SG: A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV + homeless and marginally housed people. AIDS. 2010, 24: 2835-2840. 10.1097/QAD.0b013e328340a209.CrossRefPubMedPubMedCentral Bangsberg DR, Ragland K, Monk A, Deeks SG: A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV + homeless and marginally housed people. AIDS. 2010, 24: 2835-2840. 10.1097/QAD.0b013e328340a209.CrossRefPubMedPubMedCentral
20.
go back to reference Hodder SL, Mounzer K, Dejesus E, Ebrahimi R, Grimm K, Esker S, Ecker J, Farajallah A, Flaherty JF, AI266073 Study Group: Patient reported outcomes in virologically suppressed, HIV-1-Infected subjects after switching to a simplified, single-tablet regimen of efavirenz, emtricitabine, and tenofovir DF. AIDS Patient Care STDS. 2010, 24: 87-96. 10.1089/apc.2009.0259.CrossRefPubMed Hodder SL, Mounzer K, Dejesus E, Ebrahimi R, Grimm K, Esker S, Ecker J, Farajallah A, Flaherty JF, AI266073 Study Group: Patient reported outcomes in virologically suppressed, HIV-1-Infected subjects after switching to a simplified, single-tablet regimen of efavirenz, emtricitabine, and tenofovir DF. AIDS Patient Care STDS. 2010, 24: 87-96. 10.1089/apc.2009.0259.CrossRefPubMed
21.
go back to reference 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 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
23.
go back to reference Llibre JM, Arribas JR, Domingo P, Gatell JM, Lozano F, Santos JR, Rivero A, Moreno S, Clotet B: Spanish group for FDAC evaluation. Clinical implications of fixed-dose coformulations of antiretrovirals on the outcome of HIV-1 therapy. AIDS. 2011, 25: 1683-1690. 10.1097/QAD.0b013e3283499cd9.CrossRefPubMed Llibre JM, Arribas JR, Domingo P, Gatell JM, Lozano F, Santos JR, Rivero A, Moreno S, Clotet B: Spanish group for FDAC evaluation. Clinical implications of fixed-dose coformulations of antiretrovirals on the outcome of HIV-1 therapy. AIDS. 2011, 25: 1683-1690. 10.1097/QAD.0b013e3283499cd9.CrossRefPubMed
Metadata
Title
Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients
Authors
Massimiliano Fabbiani
Mauro Zaccarelli
Pierfrancesco Grima
Mattia Prosperi
Iuri Fanti
Manuela Colafigli
Alessandro D’Avino
Annalisa Mondi
Alberto Borghetti
Massimo Fantoni
Roberto Cauda
Simona Di Giambenedetto
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-26

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