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Original article

Vol. 149 No. 1718 (2019)

Nevirapine in HIV maintenance therapy – can “old drugs” survive in current HIV management?

DOI
https://doi.org/10.4414/smw.2019.20053
Cite this as:
Swiss Med Wkly. 2019;149:w20053
Published
24.04.2019

Abstract

AIMS OF THE STUDY

Nevirapine has an exceptional record for long-term tolerability with few side effects in human immunodeficiency virus (HIV) combined antiretroviral therapy (cART). Owing to relatively frequent hypersensitivity reactions (HSR) (15–25%) in the first 3 months after treatment initiation (especially in patients with a high CD4 count (>250/µl in women, >400/µl in men)), it is being used less and less. However, the rate of adverse events is lower when patients are already under suppressive cART. We present the results of a single centre strategy to offer the switch to a nevirapine-containing regimen and evaluate the potential role nevirapine could play in current antiretroviral treatment.

METHODS

All adult HIV-positive patients starting nevirapine at our centre since 2010 were evaluated in this retrospective analysis. We examined the proportion of patients on cART containing nevirapine, as well as the number of starts and stops every 6 months. Nevirapine discontinuation rates were analysed by sex, age, hepatitis C virus (HCV) status, time on nevirapine, ethnicity, CD4 nadir as well as CD4 count, HIV-RNA and ART backbone at nevirapine start.

RESULTS

Since 2014, more than a third of our treated HIV patients have been on nevirapine-containing therapy, with a stable percentage in the following years; 277 patients starting nevirapine for the first time were analysed. Thirty-three percent (92/277) of these first nevirapine therapies were discontinued, with 16 cases (17%) resuming nevirapine later during follow-up. Of the patients who continued nevirapine for more than 90 days (n = 221), 80% maintained nevirapine until their last follow-up. The nevirapine stop rate after the first 90 days was 15-fold lower (5.4 per 100 patient years, 95% confidence interval [CI] 4.0–7.2) than in the first 90 days. Overall, nevirapine was used for a median of 2.9 years (interquartile range [IQR] 0.5–5.6). In HCV co-infected patients, the treatment stop rate was 4-fold higher than in HIV mono-infected patients, but this difference was mainly due to treatment interruptions caused by drug-drug interactions with intermittent HCV therapy. Six out of seven Asian patients experienced HSR (hepatotoxicity / skin rash). In a population with 74% 3TC/ABC backbone, 81% fully suppressed, median CD4 nadir 240/µl (IQR 120–360) and median CD4 count at nevirapine start 590/µl (IQR 400–840), both high CD4 nadir and high CD4 count at nevirapine start were associated with lower rather than higher discontinuation rates. In fully suppressed patients with high CD4 count at nevirapine start, high CD4 nadir was not a risk factor for HSR. Major reasons for the discontinuation of nevirapine were HSR (liver, skin rash) in 38 cases (41% of all discontinuations) followed by other adverse drug reactions (n = 17) and non-adherence (n = 14). In patients who stopped nevirapine after more than 90 days, the major cause was non-adherence or other adverse drug reaction (both n = 12).

CONCLUSIONS

In this study, two thirds of the patients continued nevirapine with favourable long-term tolerability and efficacy. Thus, this low-cost “old drug” may still represent a valid treatment switch option for maintenance therapy in selected patients with a fully suppressed viral load. However, further evaluation is needed.

References

  1. Joos B, Fischer M, Kuster H, Pillai SK, Wong JK, Böni J, et al.; Swiss HIV Cohort Study. HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci USA. 2008;105(43):16725–30. doi:.https://doi.org/10.1073/pnas.0804192105
  2. Gueler A, Moser A, Calmy A, Günthard HF, Bernasconi E, Furrer H, et al.; Swiss HIV Cohort Study, Swiss National Cohort. Life expectancy in HIV-positive persons in Switzerland: matched comparison with general population. AIDS. 2017;31(3):427–36.
  3. Ryom L, Boesecke C, Bracchi M, Ambrosioni J, Pozniak A, Arribas J, et al.; EACS Governing Board. Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0. HIV Med. 2018;19(5):309–15. doi:.https://doi.org/10.1111/hiv.12600
  4. Dieleman JP, Sturkenboom MC, Wit FW, Jambroes M, Mulder JW, Ten Veen JH, et al.; AIDS Therapy Evaluation, The Netherlands Study Group (ATHENA). Low risk of treatment failure after substitution of nevirapine for protease inhibitors among human immunodeficiency virus-infected patients with virus suppression. J Infect Dis. 2002;185(9):1261–8. doi:.https://doi.org/10.1086/340131
  5. Dieleman JP, Jambroes M, Gyssens IC, Sturkenboom MC, Stricker BH, Mulder WM, et al.; ATHENA Study Group. Determinants of recurrent toxicity-driven switches of highly active antiretroviral therapy. The ATHENA cohort. AIDS. 2002;16(5):737–45. doi:.https://doi.org/10.1097/00002030-200203290-00009
  6. Reekie J, Reiss P, Ledergerber B, Sedlacek D, Parczewski M, Gatell J, et al.; 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. doi:.https://doi.org/10.1111/j.1468-1293.2010.00877.x
  7. Kamara DA, Smith C, Ryom L, Reiss P, Rickenbach M, Phillips A, et al. Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels: the D:A:D study. Antivir Ther. 2016;21(6):495–506. doi:.https://doi.org/10.3851/IMP3051
  8. Calcagno A, Di Perri G, Bonora S. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system. Clin Pharmacokinet. 2014;53(10):891–906. doi:.https://doi.org/10.1007/s40262-014-0171-0
  9. Rodríguez-Arrondo F, Aguirrebengoa K, Portu J, Muñoz J, García MA, Goikoetxea J, et al. Long-term effectiveness and safety outcomes in HIV-1-infected patients after a median time of 6 years on nevirapine. Curr HIV Res. 2009;7(5):526–32. doi:.https://doi.org/10.2174/157016209789346246
  10. Sarmati L, Parisi SG, Montano M, Andreis S, Scaggiante R, Galgani A, et al. Nevirapine use, prolonged antiretroviral therapy and high CD4 nadir values are strongly correlated with undetectable HIV-DNA and -RNA levels and CD4 cell gain. J Antimicrob Chemother. 2012;67(12):2932–8. doi:.https://doi.org/10.1093/jac/dks331
  11. Montaner JS, Reiss P, Cooper D, Vella S, Harris M, Conway B, et al.; for the INCAS Study Group. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA. 1998;279(12):930–7. doi:.https://doi.org/10.1001/jama.279.12.930
  12. de Jong MD, Vella S, Carr A, Boucher CA, Imrie A, French M, et al. High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication. J Infect Dis. 1997;175(4):966–70. doi:.https://doi.org/10.1086/514002
  13. Wit FWNM, Kesselring AM, Gras L, Richter C, van der Ende ME, Brinkman K, et al. Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study. Clin Infect Dis. 2008;46(6):933–40. doi:.https://doi.org/10.1086/528861
  14. Patterson P, Socías E, Pryluka D, Lapadula P, Pérez H, Cahn P. Switching to nevirapine-based regimens after undetectable viral load is not associated with increased risk of discontinuation due to toxicity. J Int AIDS Soc. 2014;17(4, Suppl 3):19794. doi:.https://doi.org/10.7448/IAS.17.4.19794
  15. Schoeni-Affolter F, Ledergerber B, Rickenbach M, Rudin C, Günthard HF, Telenti A, et al.; Swiss HIV Cohort Study. Cohort profile: the Swiss HIV Cohort study. Int J Epidemiol. 2010;39(5):1179–89. doi:.https://doi.org/10.1093/ije/dyp321
  16. Nitika N, Mishra SS, Lohani P. Lexis Expansion: a prerequisite for analyzing time changing variables in a cohort study. Nepal J Epidemiol. 2017;7(2):681–4. doi:.https://doi.org/10.3126/nje.v7i2.17974
  17. Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018;320(4):379–96. doi:.https://doi.org/10.1001/jama.2018.8431
  18. Kesselring AM, Wit FW, Sabin CA, Lundgren JD, Gill MJ, Gatell JM, et al.; Nevirapine Toxicity Multicohort Collaboration. Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy. AIDS. 2009;23(13):1689–99. doi:.https://doi.org/10.1097/QAD.0b013e32832d3b54
  19. Ma JD, Lee KC, Kuo GM. HLA-B*5701 testing to predict abacavir hypersensitivity. PLoS Curr. 2010;2:RRN1203. doi:.https://doi.org/10.1371/currents.RRN1203
  20. de Boissieu P, Dramé M, Raffi F, Cabie A, Poizot-Martin I, Cotte L, et al.; Dat’AIDS Study Group. Long-term efficacy and toxicity of abacavir/lamivudine/nevirapine compared to the most prescribed ARV regimens before 2013 in a French Nationwide Cohort Study. Medicine (Baltimore). 2016;95(37):e4890. doi:.https://doi.org/10.1097/MD.0000000000004890
  21. Häggblom A, Lindbäck S, Gisslén M, Flamholc L, Hejdeman B, Palmborg A, et al. HIV drug therapy duration; a Swedish real world nationwide cohort study on InfCareHIV 2009-2014. PLoS One. 2017;12(2):e0171227. doi:.https://doi.org/10.1371/journal.pone.0171227
  22. May MT, Justice AC, Birnie K, Ingle SM, Smit C, Smith C, et al. Injection drug use and Hepatitis C as risk factors for mortality in HIV-infected individuals: the Antiretroviral Therapy Cohort Collaboration. J Acquir Immune Defic Syndr. 2015;69(3):348–54. doi:.https://doi.org/10.1097/QAI.0000000000000603
  23. Centers for Disease Control and Prevention (CDC). Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures--worldwide, 1997-2000. MMWR Morb Mortal Wkly Rep. 2001;49(51-52):1153–6.
  24. Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136(3):323–7. doi:.https://doi.org/10.1001/archderm.136.3.323

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