Page 71 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 6 of 7 Opinion Paper

combination STR at low cost, is safe in pregnancy and can be 4. Wilkin A, Pozniak AL, Morales-Ramirez J, et al. Long-term efficacy, safety, and
tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive
used concomitantly with rifampicin-containing TB treatment. patients: Week 192 results from a phase IIb randomized trial. AIDS Res Hum
However efavirenz causes treatment-limiting toxicity in Retrovir. 2012;28(5):437–446. https://doi.org/10.1089/aid.2011.0050
some individuals and should be used with caution in 5. Pozniak AL, Morales-Ramirez J, Katabira E, et al. Efficacy and safety of TMC278 in
antiretroviral-naive HIV-1 patients: Week 96 results of a phase IIb randomized
psychiatric disease. trial. AIDS. 2010;24(1):55–65. https://doi.org/10.1097/QAD.0b013e32833032ed
6. Molina J-M, Cahn P, Grinsztejn B, et al. Rilpivirine versus efavirenz with tenofovir
and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): A phase 3
Rilpivirine cannot replace efavirenz in standard first-line randomised double-blind active-controlled trial. Lancet. 2011;378(9787):238–246.
https://doi.org/10.1016/S0140-6736(11)60936-7
therapy. Rilpivirine is not optimal for patients with high 7. Cohen CJ, Andrade-Villanueva J, Clotet B, et al. Rilpivirine versus efavirenz with
baseline viral loads because of reduced efficacy, and cannot two background nucleoside or nucleotide reverse transcriptase inhibitors in
treatment-naive adults infected with HIV-1 (THRIVE): A phase 3, randomised, non-
be prescribed with rifampicin. In addition, there is a paucity inferiority trial. Lancet. 2011;378(9787):229–237. https://doi.org/10.1016/
of rilpivirine safety data in pregnancy, and the decrease in S0140-6736(11)60983-5
rilpivirine concentrations during pregnancy is concerning: 8. Tebas P, Sension M, Arribas J, et al. Lipid levels and changes in body fat distribution
in treatment-naive, HIV-1-infected adults treated with rilpivirine or efavirenz for
more data in pregnancy are required to inform 96 weeks in the ECHO and THRIVE trials. Clin Infect Dis. 2014;59(3):425–434.
https://doi.org/10.1093/cid/ciu234
recommendations on use in pregnancy. However, rilpivirine 9. Nelson MR, Elion RA, Cohen CJ, et al. Rilpivirine versus efavirenz in HIV-1-infected
is generally well tolerated and may be a useful alternative for subjects receiving emtricitabine/tenofovir DF: Pooled 96-week data from ECHO
and THRIVE Studies. HIV Clin Trials. 2013;14(3):81–91. https://doi.org/10.1310/
people living with HIV who cannot tolerate efavirenz or in hct1403-81
whom it is contraindicated. If rilpivirine is initiated in 10. Rimsky L, Van Eygen V, Hoogstoel A, et al. 96-week resistance analyses of
treatment-naïve patients, a baseline viral load is mandatory rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and
THRIVE phase III trials. Antivir Ther. 2013;18(8):967–977. https://doi.
because of reduced efficacy at high viral loads in phase 3 org/10.3851/IMP2636
trials, and if the baseline viral load is more than 100 000 11. Mills AM, Antinori A, Clotet B, et al. Neurological and psychiatric tolerability of
rilpivirine (TMC278) vs. efavirenz in treatment-naive, HIV-1-infected patients at
copies/mL, an alternative drug is preferable. 48 weeks. HIV Med. 2013;14(7):391–400. https://doi.org/10.1111/hiv.12012
12. Cohen C, Wohl D, Arribas JR, et al. Week 48 results from a randomized clinical trial of
rilpivirine/emtricitabine/tenofovir disoproxil fumarate vs. efavirenz/emtricitabine/
With increasing use of dolutegravir as more country tenofovir disoproxil fumarate in treatment-naive HIV-1-infected adults. AIDS.
2014;28(7):989–997. https://doi.org/10.1097/QAD.0000000000000169
programmes transition to dolutegravir-based first-line ART, 13. Cohen CJ, Molina JM, Cahn P, et al. Efficacy and safety of rilpivirine (TMC278)
emergent neuropsychiatric adverse events are being reported, versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: Pooled
suggesting an overlapping toxicity profile with current results from the phase 3 double-blind randomized ECHO and THRIVE trials. J
Acquir Immune Defic Syndr. 2012;60(1):33–42. https://doi.org/10.1097/
efavirenz-based regimens. For patients who experience QAI.0b013e31824d006e
neuropsychiatric or other toxicity or with contraindications 14. Ford N, Shubber Z, Pozniak A, et al. Comparative safety and neuropsychiatric
adverse events associated with efavirenz use in first-line antiretroviral therapy: A
to current or future first-line ART regimens, rilpivirine may systematic review and meta-analysis of randomized trials. J Acquir Immune Defic
Syndr. 2015;69(4):422–429. https://doi.org/10.1097/QAI.0000000000000606
be a useful alternative.
15. Raffi F, Pozniak AL, Wainberg MA. Has the time come to abandon efavirenz for
first-line antiretroviral therapy? J Antimicrob Chemother. 2014;69(7):1742–1747.
https://doi.org/10.1093/jac/dku058
Acknowledgements 16. Munderi P, Were E, Avihingsanon A, et al. Switching suppressed first-line patients
Competing interests to TDF/FTC/RPV is non-inferior to TDF/FTC/EFV and could be an alternative
treatment option in low- and middle-income countries. 21st International AIDS
Conference (AIDS 2016); 21 July 2016; Durban, South Africa.
Dr Michelle Moorhouse has received speaker fees and 17. Sculier D, Gayet-Ageron A, Battegay M, et al. Rilpivirine use in the Swiss HIV cohort
honoraria from Gilead Sciences, AbbVie, Cipla, Mylan study: A prospective cohort study. BMC Infect Dis. 2017;17(1):476. https://doi.
org/10.1186/s12879-017-2579-2
and Janssen, and has received conference sponsorship 18. Cazanave C, Reigadas S, Mazubert C, et al. Switch to rilpivirine/emtricitabine/
from BD, Gilead, Janssen, Merck, Cipla and Mylan. Her tenofovir single-tablet regimen of human immunodeficiency virus-1 RNA-
work forms part of ART optimisation collaborations and suppressed patients, Agence Nationale de Recherches sur le SIDA et les Hepatites
Virales CO3 Aquitaine Cohort, 2012–2014. Open Forum Infect Dis.
receives funding from USAID, Unitaid and the South 2015;2(1):ofv018. https://doi.org/10.1093/ofid/ofv018
African Medical Research Council (SAMRC) and study 19. Pinnetti C, Di Giambenedetto S, Maggiolo F, et al. Switching to coformulated
rilpivirine/emtricitabine/tenofovir in virologically suppressed patients: Data from
drug donations from ViiV Healthcare and Gilead Sciences a multicenter cohort. J Acquir Immune Defic Syndr. 2015;70(4):e147–e150.
https://doi.org/10.1097/QAI.0000000000000727
for ART optimisation studies. Prof Karen Cohen has no 20. Arrabal-Duran P, Rodriguez-Gonzalez CG, Chamorro-de-Vega E, Gijon-Vidaurreta
conflicts of interest to declare. P, Herranz-Alonso A, Sanjurjo-Saez M. Switching to a rilpivirine/emtricitabine/
tenofovir single-tablet regimen in RNA-suppressed patients infected with human
immunodeficiency virus 1: Effectiveness, safety and costs at 96 weeks. Int J Clin
Pract. 2017;71(8):12968. https://doi.org/10.1111/ijcp.12968
Authors’ contributions 21. Palella FJ, Fisher M, Tebas P, et al. SPIRIT - Switching to rilpivirine/emtricitabine/
tenofovir DF single-tablet regimen from boosted protease inhibitor maintains HIV-
M.A.M. and K.C. conceived the scope and structure of the 1 suppression through week 48. American Conference for the Treatment of HIV;
article together. M.A.M. completed the first draft. K.C. 21–23 March 2013; Denver, CO; 2013.
assisted with refining the article for submission. 22. Crauwels H, Van Heeswijk RP, Stevens M, et al. Clinical perspective on drug-drug
interactions with the non-nucleoside reverse transcriptase inhibitor rilpivirine.
AIDS Rev. 2013;15(2):87–101.
References 23. Van Heeswijk R, Hoetelmans RMW, Kestens D, et al. The effects of CYP3A4
modulation on the pharmacokinetics of TMC278, an investigational non-
nucleoside reverse transcriptase inhibitor (NNRTI). Seventh International
1. Williams I, Churchill D, Anderson J, et al. British HIV Association guidelines for the Workshop of Clinical Pharmacology; 20–22 April 2006; Lisbon, Portugal; 2006.
treatment of HIV1-positiveadults with antiretroviral therapy 2012 (Updated 24. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil
November 2013). HIV Med. 2014;15(Suppl 1):1–85. fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial
2. European AIDS Clinical Society. EACS guidelines 2017 [homepage on the Internet]. treatment of HIV-1 infection: Two randomised, double-blind, phase 3, non-
2017 [updated October 2017]. Version 9.0. Available from: http://www. inferiority trials. Lancet. 2015;385(9987):2606–2615. https://doi.org/10.1016/
eacsociety.org/files/guidelines_9.0-english.pdf S0140-6736(15)60616-X
3. Meintjes G, Moorhouse M, Carmona S, et al. Southern African HIV Clinicians 25. Venter WDF, Kaiser B, Pillay Y, et al. Cutting the cost of South African antiretroviral
Society Adult antiretroviral therapy guidelines 2017. S Afr J HIV Med. therapy using newer, safer drugs. SAMJ. 2017;107(1):28–30. https://doi.
2017;18(1):a776. https://doi.org/10.4102/sajhivmed.v18i1.776 org/10.7196/SAMJ.2017.v107i1.12058
http://www.sajhivmed.org.za 64 Open Access