HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients

  • Arezoo Marjani
  • Farah Bokharaei-SalimEmail author
  • Fatemeh Jahanbakhshi
  • Seyed Hamidreza Monavari
  • Maryam Esghaei
  • Saeed Kalantari
  • Seyed Jalal Kiani
  • Angila Ataei-Pirkooh
  • Atousa Fakhim
  • Hossein Keyvani
Original Article


The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35_AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.



All authors of the present survey would like to thank all of the participants who generously enrolled.


The present research was funded by Research Deputy of IUMS, Tehran, Iran, with grant number 33002.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The present research was approved by the Iran University of Medical Sciences (IUMS) Ethical Committee (ethical code: IR.IUMS.FMD.REC 1397.083). All of the study subjects were informed about this research, and a written consent form was obtained from them.


  1. 1.
    Riemenschneider M, Heider D (2016) Current approaches in computational drug resistance prediction in HIV. Curr HIV Res 14(4):307–315PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Blood GAC (2016) Human immunodeficiency virus (HIV). Transfus Med Hemotherapy 43(3):203CrossRefGoogle Scholar
  3. 3.
    Melhuish A, Lewthwaite P (2018) Natural history of HIV and AIDS. Medicine. 46(6):356–361CrossRefGoogle Scholar
  4. 4.
  5. 5.
    Weber IT, Harrison RW (2016) Tackling the problem of HIV drug resistance. Adv Biochem. 62:273–279Google Scholar
  6. 6.
    Brenner BG, Wainberg MA (2017) Clinical benefit of dolutegravir in HIV-1 management related to the high genetic barrier to drug resistance. Virus Res 239:1–9PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Rossouw TM, Nieuwoudt M, Manasa J, Malherbe G, Lessells RJ, Pillay S et al (2017) HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa. HIV Med 18(2):104–114PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Rosemary A, Chika O, Jonathan O, Godwin I, Georgina O, Azuka O et al (2018) Genotyping performance evaluation of commercially available HIV-1 drug resistance test. PLoS One 13(6):e0198246PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Michaud V, Bar-Magen T, Turgeon J, Flockhart D, Desta Z, Wainberg MA (2012) The dual role of pharmacogenetics in HIV treatment: mutations and polymorphisms regulating antiretroviral drug resistance and disposition. Pharmacol Rev 64(3):803–833PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
  11. 11.
    Tetteh RA, Yankey BA, Nartey ET, Lartey M, Leufkens HG, Dodoo AN (2017) Pre-exposure prophylaxis for HIV prevention: safety concerns. Drug saf 40(4):273–83PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Clutter DS, Jordan MR, Bertagnolio S, Shafer RW (2016) HIV-1 drug resistance and resistance testing. Infect Genetics Evol 46:292–307CrossRefGoogle Scholar
  13. 13.
  14. 14.
    Jeong W, Jung IY, Choi H, Kim JH, Seong H, Ahn JY et al (2019) Integrase strand transfer inhibitor resistance mutations in antiretroviral therapy-naive and treatment-experienced HIV patients in South Korea. AIDS Res Hum Retroviruses 35(2):213–6PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF et al (2013) Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 382(9893):700–708PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kim Y, Chin BS, Kim G, Shin HS (2018) Integrase strand transfer inhibitor resistance mutations in antiretroviral treatment-naive patients in Korea: a prospective, observational study. J Korean Med Sci 33(25):e173PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Vahabpour R, Bokharaei-Salim F, Kalantari S, Garshasbi S, Monavari SH, Esghaei M et al (2017) HIV-1 genetic diversity and transmitted drug resistance frequency among Iranian treatment-naive, sexually infected individuals. Adv Virol 162(6):1477–1485Google Scholar
  18. 18.
    Manosuthi W, Ongwandee S, Bhakeecheep S, Leechawengwongs M, Ruxrungtham K, Phanuphak P et al (2015) Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand. AIDS Res Ther 12:12PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Heger E, Theis AA, Remmel K, Walter H, Pironti A, Knops E et al (2016) Development of a phenotypic susceptibility assay for HIV-1 integrase inhibitors. J Virol Methods 238:29–37PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Harada S, Yoshimura K, Yamaguchi A, Boonchawalit S, Yusa K, Matsushita S (2013) Impact of antiretroviral pressure on selection of primary human immunodeficiency virus type 1 envelope sequences in vitro. J Gen Virol 94(Pt 5):933–943PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Bennett DE, Camacho RJ, Otelea D, Kuritzkes DR, Fleury H, Kiuchi M et al (2009) Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 4(3):e4724PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Bradley-Stewart A, Urcia C, MacLean A, Aitken C, Gunson R (2017) HIV-1 integrase inhibitor resistance among treatment naïve patients in the West of Scotland. J Clin Virol 92:7–10PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Casadellà M, Van Ham P, Noguera-Julian M, Van Kessel A, Pou C, Hofstra L et al (2015) Primary resistance to integrase strand-transfer inhibitors in Europe. J Antimicrob Chemother 70(10):2885–2888PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Stekler JD, McKernan J, Milne R, Tapia KA, Mykhalchenko K, Holte S et al (2015) Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007–2013. Antiviral therapy. 20(1):77PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Inzaule SC, Hamers RL, Noguera-Julian M, Casadellà M, Parera M, Rinke de Wit TF et al (2018) Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa. J Antimicrob Chemother 73(5):1167–1172PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Lepik KJ, Harrigan PR, Yip B, Wang L, Robbins MA, Zhang WW et al (2017) Emergent drug resistance with integrase strand transfer inhibitor-based regimens. Aids. 31(10):1425–1434PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    European AIDS Clinical Society guidelines (2017). Updated 2016. Accessed 31 May 2017 (online)
  28. 28.
    Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (2017). Updated 2016. Accessed 31 May 2017 (online)
  29. 29.
    Steigbigel RT, Cooper DA, Teppler H, Eron JJ, Gatell JM, Kumar PN et al (2010) Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin infect Dis 50(4):605–612PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Eron JJ, Cooper DA, Steigbigel RT, Clotet B, Gatell JM, Kumar PN et al (2013) Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies: final results of two randomised, placebo-controlled trials. Lancet Infect Dis 13(7):587–596PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Hurt CB, Sebastian J, Hicks CB, Eron JJ (2014) Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012. Clin Infect Dis 58(3):423–431PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Farrokhi M, Moallemi S, Baesi K, Ahsani-Nasab S, Gholami M, Sadeghi L et al (2016) HIV drug resistance and phylogeny profile in naive and antiretroviral-experienced patients in Tehran, Iran. Intervirology 59(3):131–136PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C et al (2013) Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 381(9868):735–743PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    De Clercq E, Li G (2016) Approved antiviral drugs over the past 50 years. Clin Microbiol Rev 29(3):695–747PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kandel CE, Walmsley SL (2015) Dolutegravir–a review of the pharmacology, efficacy, and safety in the treatment of HIV. Drug Des Dev Ther 9:3547CrossRefGoogle Scholar
  36. 36.
    Tsiang M, Jones GS, Goldsmith J, Mulato A, Hansen D, Kan E et al (2016) Antiviral activity of bictegravir (GS-9883), a novel potent HIV-1 integrase strand transfer inhibitor with an improved resistance profile. Antimicrob Agents Chemother 60(12):7086–7097PubMedPubMedCentralGoogle Scholar
  37. 37.
    Smith SJ, Zhao XZ, Burke TR, Hughes SH (2018) Efficacies of cabotegravir and bictegravir against drug-resistant HIV-1 integrase mutants. Retrovirology. 15(1):37PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Oliveira M, Ibanescu R-I, Anstett K, Mésplède T, Routy J-P, Robbins MA et al (2018) Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Retrovirology. 15(1):56PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Gubavu C, Prazuck T, Niang M, Buret J, Mille C, Guinard J et al (2015) Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients. J Antimicrob Chemother 71(4):1046–1050PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Liedtke MD, Tomlin CR, Lockhart SM, Miller MM, Rathbun RC (2014) Long-term efficacy and safety of raltegravir in the management of HIV infection. Infect Drug Resist 7:73PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    van Lunzen J, Maggiolo F, Arribas JR, Rakhmanova A, Yeni P, Young B et al (2012) Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis 12(2):111–118PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D et al (2012) Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 379(9835):2439–2448PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Eron JJ Jr, Rockstroh JK, Reynes J, Andrade-Villanueva J, Ramalho-Madruga JV, Bekker LG et al (2011) Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis 11(12):907–915PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutiérrez F et al (2013) Dolutegravir plus abacavir–lamivudine for the treatment of HIV-1 infection. N Engl J Med 369(19):1807–1818PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Clotet B, Feinberg J, Van Lunzen J, Khuong-Josses M-A, Antinori A, Dumitru I et al (2014) Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 383(9936):2222–2231PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM et al (2013) Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis 13(11):927–935PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Castagna A, Maggiolo F, Penco G, Wright D, Mills A, Grossberg R et al (2014) Dolutegravir in antiretroviral-experienced patients with raltegravir-and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study. J Infect Dis 210(3):354–362PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Eron JJ, Clotet B, Durant J, Katlama C, Kumar P, Lazzarin A et al (2012) Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study. J Infect Dis 207(5):740–748PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ndashimye E, Avino M, Kyeyune F, Nankya I, Gibson RM, Nabulime E et al (2018) Absence of HIV-1 drug resistance mutations supports the use of dolutegravir in Uganda. AIDS Res Hum Retroviruses 34(5):404–414PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Tsai H-C, Chen I-T, Wu K-S, Tseng Y-T, Sy C-L, Chen J-K et al (2018) HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan. Oncotarget. 9(38):24927PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Alaoui N, El Alaoui MA, Touil N, El Annaz H, Melloul M, Tagajdid R et al (2018) Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco. BMC Res Notes 11(1):369PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Rusconi S, Adorni F, Tau P, Borghi V, Pecorari M, Maserati R et al (2018) Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): durability and virological response in a large Italian HIV drug resistance network (ARCA). J Clin Virol 105:112–117PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    George JM, Kuriakose SS, Dee N, Stoll P, Lalani T, Dewar R et al (eds) (2018) Rapid development of high-level resistance to dolutegravir with emergence of T97A mutation in 2 treatment-experienced individuals with baseline partial sensitivity to dolutegravir. Open forum infectious diseases. Oxford University Press, OxfordGoogle Scholar
  54. 54.
    Brado D, Obasa AE, Ikomey GM, Cloete R, Singh K, Engelbrecht S et al (2018) Author Correction: Analyses of HIV-1 integrase sequences prior to South African national HIV-treatment program and availability of integrase inhibitors in Cape Town, South Africa. Sci Rep 8(1):6262PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Zoufaly A, Kraft C, Schmidbauer C, Puchhammer-Stoeckl E (2017) Prevalence of integrase inhibitor resistance mutations in Austrian patients recently diagnosed with HIV from 2008 to 2013. Infection 45(2):165–170PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Tostevin A, White E, Dunn D, Croxford S, Delpech V, Williams I et al (2017) Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. HIV Med 18(3):204–213PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Farrokhi M, Moallemi S, Shirkoohi R, Golmohammadi R, Ahsani-Nasab S, Sardashti S et al (2017) Antiretroviral drug resistance mutations among HIV treatment failure patients in Tehran, Iran. Iran J Public Health 46(9):1256–1264PubMedPubMedCentralGoogle Scholar
  58. 58.
    Baesi K, Moallemi S, Farrokhi M, Alinaghi SA, Truong HM (2014) Subtype classification of Iranian HIV-1 sequences registered in the HIV databases, 2006-2013. PLoS One 9(9):e105098PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Golmohammadi R, Baesi K, Moradi A, Farrokhi M, McFarland W, Parsamajd S (2017) The first characterization of HIV-1 subtypes and drug resistance mutations among antiretrovirally treated patients in Kermanshah, Iran. Intervirology 60(1–2):33–37PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Jahanbakhsh F, Ibe S, Hattori J, Monavari SH, Matsuda M, Maejima M et al (2013) Molecular epidemiology of HIV type 1 infection in Iran: genomic evidence of CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use. AIDS Res Hum Retroviruses 29(1):198–203PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Fox MP, Cutsem GV, Giddy J, Maskew M, Keiser O, Prozesky H et al (2012) Rates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in South Africa. J Acquir Immune Defic Syndr 60(4):428–437PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Boulle A, Van Cutsem G, Hilderbrand K, Cragg C, Abrahams M, Mathee S et al (2010) Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 24(4):563–572PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Joseph Davey D, Abrahams Z, Feinberg M, Prins M, Serrao C, Medeossi B et al (2018) Factors associated with recent unsuppressed viral load in HIV-1-infected patients in care on first-line antiretroviral therapy in South Africa. Int J STD AIDS 29(6):603–610PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Rangarajan S, Donn JC, le Giang T, Bui DD, Hung Nguyen H, Tou PB et al (2016) Factors associated with HIV viral load suppression on antiretroviral therapy in Vietnam. J Virus Erad 2(2):94–101PubMedPubMedCentralGoogle Scholar
  65. 65.
    Floridia M, Giuliano M, Palmisano L, Vella S (2008) Gender differences in the treatment of HIV infection. Pharmacol Res 58(3–4):173–182PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Prins M, Meyer L, Hessol NA (2005) Sex and the course of HIV infection in the pre- and highly active antiretroviral therapy eras. AIDS. 19(4):357–370PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Bastard M, Fall MB, groupe d’etude de la Cohorte A (2014) Long term adherence to HAART in Senegal. Bull de la Soc de Pathol Exotique 107(4):241–243Google Scholar
  68. 68.
    Bastard M, Fall MB, Laniece I, Taverne B, Desclaux A, Ecochard R et al (2011) Revisiting long-term adherence to highly active antiretroviral therapy in Senegal using latent class analysis. J Acquir Immune Defic Syndr 57(1):55–61PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Shoko C, Chikobvu D (2019) A superiority of viral load over CD4 cell count when predicting mortality in HIV patients on therapy. BMC Infect Dis 19(1):169PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Salazar-Vizcaya L, Keiser O, Karl T, Davies MA, Haas AD, Blaser N et al (2014) Viral load versus CD4(+) monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa: a cohort-based modelling study. AIDS. 28(16):2451–2460PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Brown ER, Otieno P, Mbori-Ngacha DA, Farquhar C, Obimbo EM, Nduati R et al (2009) Comparison of CD4 cell count, viral load, and other markers for the prediction of mortality among HIV-1-infected Kenyan pregnant women. J Infect Dis 199(9):1292–1300PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Hoffmann CJ, Charalambous S, Thio CL, Martin DJ, Pemba L, Fielding KL et al (2007) Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B. AIDS. 21(10):1301–1308PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Zhou J, Sirisanthana T, Kiertiburanakul S, Chen YM, Han N, Lim PL et al (2010) Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database. BMC Infect Dis 10:361PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T et al (1999) Latent infection of CD4 + T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5(5):512–517PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Ledergerber B, Lundgren JD, Walker AS, Sabin C, Justice A, Reiss P et al (2004) Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet 364(9428):51–62PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Mocroft A, Phillips AN, Ledergerber B, Smith C, Bogner JR, Lacombe K et al (2010) Estimated average annual rate of change of CD4(+) T-cell counts in patients on combination antiretroviral therapy. Antivir Ther. 15(4):563–570PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Iacob SA, Iacob DG, Jugulete G (2017) Improving the adherence to antiretroviral therapy, a difficult but essential task for a successful hiv treatment-clinical points of view and practical considerations. Front Pharmacol 8:831PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Hinkin CH, Barclay TR, Castellon SA, Levine AJ, Durvasula RS, Marion SD et al (2007) Drug use and medication adherence among HIV-1 infected individuals. AIDS Behav 11(2):185–194PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Wood E, Montaner JS, Yip B, Tyndall MW, Schechter MT, O’Shaughnessy MV et al (2003) Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users. CMAJ 169(7):656–661Google Scholar
  80. 80.
    Uthman OA, Oladimeji O, Nduka C (2017) Adherence to antiretroviral therapy among HIV-infected prisoners: a systematic review and meta-analysis. AIDS Care. 29(4):489–497PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Hansana V, Sanchaisuriya P, Durham J, Sychareun V, Chaleunvong K, Boonyaleepun S et al (2013) Adherence to antiretroviral therapy (ART) among people living with HIV (PLHIV): a cross-sectional survey to measure in Lao PDR. BMC Public Health. 13:617PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Gao X, Nau DP (2000) Congruence of three self-report measures of medication adherence among HIV patients. Ann Pharmacother 34(10):1117–1122PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Cauldbeck MB, O’Connor C, O’Connor MB, Saunders JA, Rao B, Mallesh VG et al (2009) Adherence to anti-retroviral therapy among HIV patients in Bangalore, India. AIDS Res Ther 6:7PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Arezoo Marjani
    • 1
  • Farah Bokharaei-Salim
    • 1
    Email author
  • Fatemeh Jahanbakhshi
    • 2
  • Seyed Hamidreza Monavari
    • 1
  • Maryam Esghaei
    • 1
  • Saeed Kalantari
    • 3
  • Seyed Jalal Kiani
    • 1
  • Angila Ataei-Pirkooh
    • 1
  • Atousa Fakhim
    • 4
  • Hossein Keyvani
    • 1
  1. 1.Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
  2. 2.Department of VirologyPasteur Institute of IranTehranIran
  3. 3.Departments of Infectious Diseases and Tropical MedicineIran University of Medical SciencesTehranIran
  4. 4.Department of Architectural Engineering, Faculty of EngineeringIslamic Azad University, South Tehran BranchTehranIran

Personalised recommendations