The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children

Page: [397 - 407] Pages: 11

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Abstract

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs.

Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated.

Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database.

Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children.

Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

Keywords: HIV-1, antiretroviral therapy (ART), drug resistance mutations (DRMs), HIV-1- infected, Treatment-naïve Children, transmitted drug resistance (TDR).

Graphical Abstract

[1]
Nachman SA, Lindsey JC, Moye J, et al. Growth of human immunodeficiency virus-infected children receiving highly active antiretroviral therapy. Pediatr Infect Dis J 2005; 24(4): 352-7.
[http://dx.doi.org/10.1097/01.inf.0000157095.75081.43] [PMID: 15818296]
[2]
Fields B, Knipe D, Howley P. Fields virology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins 2013.
[3]
Mazloomy SS, Shirvani AM, Dehghani TA, Tabibnezhad N, Sheykhha M. Knowledge and attitude about HIV/AIDS among pregnant women in Yazd, Iran. Iran J Reprod Med 2006; 4(1): 29-33.
[4]
Sinha S, Shekhar RC, Ahmad H, et al. Prevalence of HIV drug resistance mutation in the northern Indian population after failure of the first line antiretroviral therapy. Curr HIV Res 2012; 10(6): 532-8.
[http://dx.doi.org/10.2174/157016212802429785] [PMID: 22716105]
[5]
Jahanbakhsh F, Hattori J, Matsuda M, et al. Prevalence of transmitted HIV drug resistance in Iran between 2010 and 2011. PLoS One 2013; 8(4) e61864
[http://dx.doi.org/10.1371/journal.pone.0061864] [PMID: 23626742]
[6]
Kamarulzaman A. Fighting the HIV epidemic in the Islamic world. Lancet 2013; 381(9883): 2058-60.
[http://dx.doi.org/10.1016/S0140-6736(13)61033-8] [PMID: 23769216]
[7]
McIntosh K, Shevitz A, Zaknun D, et al. Age- and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency virus. Pediatr Infect Dis J 1996; 15(12): 1087-91.
[http://dx.doi.org/10.1097/00006454-199612000-00006] [PMID: 8970217]
[8]
Ndashimye E, Arts EJ. The urgent need for more potent antiretroviral therapy in low-income countries to achieve UNAIDS 90-90-90 and complete eradication of AIDS by 2030. Infect Dis Poverty 2019; 8(1): 63.
[http://dx.doi.org/10.1186/s40249-019-0573-1] [PMID: 31370888]
[9]
Zuo L, Peng K, Hu Y, Xu Q. Genotypic Methods for HIV Drug Resistance Monitoring: the Opportunities and Challenges Faced by China. Curr HIV Res 2019. Epub ahead of print
[http://dx.doi.org/10.2174/1570162X17666190927154110] [PMID: 31560290]
[10]
Clutter DS, Jordan MR, Bertagnolio S, Shafer RW. HIV-1 drug resistance and resistance testing. Infect Genet Evol 2016; 46: 292-307.
[11]
Larder BA. Interactions between drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. J Gen Virol 1994; 75(Pt 5): 951-7.
[http://dx.doi.org/10.1099/0022-1317-75-5-951] [PMID: 7513745]
[12]
Bennett DE, Bertagnolio S, Sutherland D, Gilks CF. The World Health Organization’s global strategy for prevention and assessment of HIV drug resistance. Antivir Ther (Lond) 2008; 13(Suppl. 2): 1-13.
[PMID: 18578063]
[13]
Hearps AC, Ryan CE, Morris LM, Plate MM, Greengrass V, Crowe SM. Stability of dried blood spots for HIV-1 drug resistance analysis. Curr HIV Res 2010; 8(2): 134-40.
[http://dx.doi.org/10.2174/157016210790442740] [PMID: 20163343]
[14]
Waldman G, Rawlings SA, Kerr J, et al. Successful optimization of antiretroviral regimens in treatment-experienced people living with HIV undergoing liver transplantation Transplant infectious disease: An official journal of the Transplantation Society. 2019. e13174
[http://dx.doi.org/10.1111/tid.13174]
[15]
Memarnejadian A, Nikpoor AR, Davoodian N, Kargar A, Mirzadeh Y, Gouklani H. HIV-1 Drug Resistance Mutations among Antiretroviral Drug-Experienced Patients in the South of Iran. Intervirology 2019; 62(2): 72-9.
[http://dx.doi.org/10.1159/000501255] [PMID: 31311021]
[16]
Petropoulos CJ, Parkin NT, Limoli KL, et al. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob Agents Chemother 2000; 44(4): 920-8.
[http://dx.doi.org/10.1128/AAC.44.4.920-928.2000] [PMID: 10722492]
[17]
Woods CK, Brumme CJ, Liu TF, et al. Automating HIV drug resistance genotyping with RECall, a freely accessible sequence analysis tool. J Clin Microbiol 2012; 50(6): 1936-42.
[http://dx.doi.org/10.1128/JCM.06689-11]
[18]
World health Organization WHO HIV drug resistance report-2012 Available from. https://www.who.int/hiv/pub/drugresistance/report2012/en/
[19]
Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA 2012; 308(4): 387-402.
[http://dx.doi.org/10.1001/jama.2012.7961] [PMID: 22820792]
[20]
Paton NI, Kityo C, Hoppe A, et al. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med 2014; 371(3): 234-47.
[http://dx.doi.org/10.1056/NEJMoa1311274] [PMID: 25014688]
[21]
Kumarasamy N, Aga E, Ribaudo HJ, et al. Lopinavir/ritonavir monotherapy as second-line antiretroviral treatment in resource-limited settings: week 104 analysis of AIDS Clinical Trials Group (ACTG) A5230. Clin Infect Dis 2015; 60(10): 1552-8.
[http://dx.doi.org/10.1093/cid/civ109] [PMID: 25694653]
[22]
DiazGranados CA, Mantilla M, Lenis W. Antiretroviral drug resistance in HIV-infected patients in Colombia. Int J Infect Dis 2010; 14(4): e298-303.
[http://dx.doi.org/10.1016/j.ijid.2009.05.006] [PMID: 19665910]
[23]
Grinsztejn B, Hughes MD, Ritz J, et al. Third-line antiretroviral therapy in low-income and middle-income countries (ACTG A5288): a prospective strategy study. Lancet HIV 2019; 6(9): e588-600.
[http://dx.doi.org/10.1016/S2352-3018(19)30146-8] [PMID: 31371262]
[24]
Bakhouch K, Oulad-Lahcen A, Bensghir R, et al. The prevalence of resistance-associated mutations to protease and reverse transcriptase inhibitors in treatment-naïve (HIV1)-infected individuals in Casablanca, Morocco. J Infect Dev Ctries 2009; 3(5): 380-91.
[http://dx.doi.org/10.3855/jidc.247] [PMID: 19759509]
[25]
Dharmalingam T, Udhaya V, Umaarasu T, Elangovan V, Rajesh SV, Shanmugam G. Prediction of drug-resistance using genotypic and docking analysis among anti-retroviral therapy naïve and first-line treatment failures in Salem, Tamil Nadu, India. Curr HIV Res 2015; 13(2): 160-72.
[http://dx.doi.org/10.2174/1570162X1302150415111040] [PMID: 25892414]
[26]
Camargo CC, Cavassan NRV, Tasca KI, Meneguin S, Miot HA, Souza LR. Depression and Coping Are Associated with Failure of Adherence to Antiretroviral Therapy Among People Living with HIV/AIDS. AIDS Res Hum Retroviruses 2019.
[http://dx.doi.org/10.1089/aid.2019.0050] [PMID: 31592722]
[27]
Chen H, Luo L, Pan SW, et al. HIV Epidemiology and Prevention in Southwestern China: Trends from 1996-2017. Curr HIV Res 2019; 17(2): 85-93.
[http://dx.doi.org/10.2174/1570162X17666190703163838] [PMID: 31269884]
[28]
Gylfason T. Natural resources, education, and economic development. Eur Econ Rev 2001; 45(4-6): 847-59.
[http://dx.doi.org/10.1016/S0014-2921(01)00127-1]
[29]
Joulaei H, Motazedian N. Primary health care strategic key to control HIV/AIDS in Iran. Iran J Public Health 2013; 42(5): 540-1.
[PMID: 23802115]
[30]
García-Deltoro M. Rapid Initiation of Antiretroviral Therapy after HIV Diagnosis. AIDS Rev 2019; 21(2): 55-64.
[http://dx.doi.org/10.24875/AIDSRev.M19000027] [PMID: 31332395]
[31]
Neshumaev D, Lebedev A, Malysheva M, et al. Molecular Surveillance of HIV-1 Infection in Krasnoyarsk Region, Russia: Epidemiology, Phylodynamics and Phylogeography. Curr HIV Res 2019; 17(2): 114-25.
[http://dx.doi.org/10.2174/1570162X17666190618155816] [PMID: 31210113]
[32]
Piot P. Joint United Nations Program on HIV/AIDS (UNAIDS). Cancer, AIDS, and Quality of Life 1997; pp. 7-10.
[33]
Ngo-Malabo ET, Ngoupo PA, Sadeuh-Mba SA, et al. HIV Drug Resistance Testing in a Resource Limited Setting with High Viral Diversity: The First Twenty Eight Months Experience. Curr HIV Res 2017; 15(4): 297-305.
[http://dx.doi.org/10.2174/1570162X15666170725143835] [PMID: 28745207]
[34]
Maskew M, Bor J, MacLeod W, Carmona S, Sherman GG, Fox MP. Adolescent HIV treatment in South Africa’s national HIV programme: a retrospective cohort study. Lancet HIV 2019; 6(11): e760-8.
[http://dx.doi.org/10.1016/S2352-3018(19)30234-6] [PMID: 31585836]
[35]
Organization WH. Global Programme on AIDS: Consensus statement from the WHO/UNICEF Consultation on HIV Transmission and Breast-feeding. Weekly Epidemiological Record= Relevé épidémiologique hebdomadaire 1992; 67(24): 177-9.
[36]
Majid T, Farhad Y, Sorour A, et al. Preventing mother-to-child transmission of HIV/AIDS: do Iranian pregnant mothers know about it? J Reprod Infertil 2010; 11(1): 53-7.
[PMID: 23926481]
[37]
Alex D, Raj Williams TI, Sachithanandham J, et al. Performance of a Modified In-House HIV-1 Avidity Assay among a Cohort of Newly Diagnosed HIV-1 Infected Individuals and the Effect of ART on the Maturation of HIV-1 Specific Antibodies. Curr HIV Res 2019; 17(2): 134-45.
[http://dx.doi.org/10.2174/1570162X17666190712125606] [PMID: 31309891]
[38]
Ganeshan S, Dickover RE, Korber BT, Bryson YJ, Wolinsky SM. Human immunodeficiency virus type 1 genetic evolution in children with different rates of development of disease. J Virol 1997; 71(1): 663-77.
[PMID: 8985398]
[39]
Shearer WT, Quinn TC, LaRussa P, et al. Viral load and disease progression in infants infected with human immunodeficiency virus type 1. N Engl J Med 1997; 336(19): 1337-42.
[http://dx.doi.org/10.1056/NEJM199705083361901] [PMID: 9134873]
[40]
Alikhani A, Morin H, Matte S, Alikhani P, Tremblay C, Durand M. Association between lipodystrophy and length of exposure to ARTs in adult HIV-1 infected patients in Montreal. BMC Infect Dis 2019; 19(1): 820.
[http://dx.doi.org/10.1186/s12879-019-4446-9] [PMID: 31533648]
[41]
Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 2009; 4(3) e4724
[http://dx.doi.org/10.1371/journal.pone.0004724] [PMID: 19266092]
[42]
Baesi K, Ravanshad M, Safari MG, Saberfar E, Hajiabdolbaghi M. Survey of Human Immunodeficiency Virus-1 Protease Gene Drug Resistance among HIV-infected Patients in an Iranian Research Center for HIV/AIDS. Pathobiology Research 2012; 14(4): 13-20.
[43]
Geretti AM, Armenia D, Ceccherini-Silberstein F. Emerging patterns and implications of HIV-1 integrase inhibitor resistance. Curr Opin Infect Dis 2012; 25(6): 677-86.
[http://dx.doi.org/10.1097/QCO.0b013e32835a1de7] [PMID: 23086187]
[44]
Lindsey JC, Malee KM, Brouwers P, Hughes MD. Neurodevelopmental functioning in HIV-infected infants and young children before and after the introduction of protease inhibitor-based highly active antiretroviral therapy. Pediatrics 2007; 119(3): e681-93.
[http://dx.doi.org/10.1542/peds.2006-1145] [PMID: 17296781]
[45]
Candotti D, Temple J, Owusu-Ofori S, Allain J-P. Multiplex real-time quantitative RT-PCR assay for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1. J Virol Methods 2004; 118(1): 39-47.
[http://dx.doi.org/10.1016/j.jviromet.2004.01.017] [PMID: 15158067]
[46]
Keyvani H, Taghinezhad Saroukalaei S, Mohseni AH. Assessment of the human cytomegalovirus UL97 gene for identification of resistance to ganciclovir in iranian immunosuppressed patients. Jundishapur J Microbiol 2016; 9(5) e31733
[http://dx.doi.org/10.5812/jjm.31733] [PMID: 27540455]
[47]
Coovadia A, Hunt G, Abrams EJ, et al. Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy. Clin Infect Dis 2009; 48(4): 462-72.
[http://dx.doi.org/10.1086/596486] [PMID: 19133804]
[48]
Mohamad S, Deris ZZ, Yusoff NK, Ariffin TAATM, Shueb RH. Assessing subtypes and drug resistance mutations among HIV-1 infected children who failed antiretroviral therapy in Kelantan, Malaysia. Braz J Infect Dis 2012; 16(3): 284-8.
[http://dx.doi.org/10.1016/S1413-8670(12)70325-2] [PMID: 22729198]
[49]
Rogo T, DeLong AK, Chan P, Kantor R. Antiretroviral treatment failure, drug resistance, and subtype diversity in the only pediatric HIV clinic in Rhode Island. Clin Infect Dis 2015; 60(9): 1426-35.
[http://dx.doi.org/10.1093/cid/civ058] [PMID: 25637585]
[50]
Neubert J, Michalsky N, Laws H-J, Borkhardt A, Jensen B, Lübke N. HIV-1 subtype diversity and prevalence of primary drug resistance in a single-center pediatric cohort in Germany. Intervirology 2016; 59(5-6): 301-6.
[http://dx.doi.org/10.1159/000477811] [PMID: 28675900]
[51]
Rojas Sánchez P, Domínguez S, Jiménez De Ory S, et al. Trends in drug resistance prevalence, HIV-1 variants and clinical status in HIV-1-infected pediatric population in Madrid: 1993 to 2015 analysis. Pediatr Infect Dis J 2018; 37(3): e48-57.
[http://dx.doi.org/10.1097/INF.0000000000001760] [PMID: 28991889]
[52]
Frange P, Chaix M-L, Veber F, Blanche S. Missed opportunities for HIV testing in pregnant women and children living in France. Pediatr Infect Dis J 2014; 33(2): e60-2.
[http://dx.doi.org/10.1097/INF.0b013e3182a09120] [PMID: 24108234]
[53]
Nesheim SR, FitzHarris LF, Mahle Gray K, Lampe MA. Epidemiology of Perinatal HIV Transmission in the United States in the Era of Its Elimination. Pediatr Infect Dis J 2019; 38(6): 611-6.
[http://dx.doi.org/10.1097/INF.0000000000002290] [PMID: 30724833]
[54]
Nesheim SR, Wiener J, Fitz Harris LF, Lampe MA, Weidle PJ. Brief Report: Estimated Incidence of Perinatally Acquired HIV Infection in the United States, 1978-2013. J Acquir Immune Defic Syndr 2017; 76(5): 461-4.
[55]
HIV Surveillance Report. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data: United States and 6 dependent areas 2016; 23(4)Available form. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-supplemental-report-vol-23-4.pdf
[56]
Nduati EW, Hassan AS, Knight MG, et al. Outcomes of prevention of mother to child transmission of the human immunodeficiency virus-1 in rural Kenya--a cohort study. BMC Public Health 2015; 15: 1008.
[http://dx.doi.org/10.1186/s12889-015-2355-4] [PMID: 26433396]
[57]
WHO Treatment of children living with HIV 2016.Available form. https://www.who.int/hiv/topics/paediatric/en/
[58]
Khazaei S, Mansori K, Soheilyzad M, Ayubi E. Challenges and proposed actions for HIV/AIDS control among children in Iran. Int J Pediatr 2016; 4(8): 2295-7.
[59]
Behboodi-Moghadam Z, Khalajinia Z, Nasrabadi AR, Mohraz M, Gharacheh M. Pregnancy through the Lens of Iranian Women with HIV: A Qualitative Study. J Int Assoc Provid AIDS Care 2016; 15(2): 148-52.
[http://dx.doi.org/10.1177/2325957415593636] [PMID: 26156585]
[60]
UNAIDS (2016) 'Fact sheet -Latest statistics on the status of the AIDS epidemic 2016.Available form. http://wwwunaidsorg/en/resources/fact-sheet
[61]
Olugbenga-Bello A, Adebimpe W, Osundina F, Abdulsalam S. Perception on prevention of mother-to-child-transmission (PMTCT) of HIV among women of reproductive age group in Osogbo, Southwestern Nigeria. Int J Womens Health 2013; 5: 399-405.
[http://dx.doi.org/10.2147/IJWH.S45815] [PMID: 23874124]
[62]
Islamic Republic of Iran AIDS Progress Report 2015 Available form. https://www.unaids.org/sites/default/files/country/documents/IRN_narrative_report_2015.pdf
[63]
Bokharaei-Salim F, Kalantari S, Gholamypour Z, et al. Investigation of the effects of a prevention of mother-to-child HIV transmission program among Iranian neonates. Arch Virol 2018; 163(5): 1179-85.
[http://dx.doi.org/10.1007/s00705-017-3661-1] [PMID: 29383588]
[64]
Guimarães PM, Ferreira JL, Coelho LP, et al. Transmitted drug resistance among recently diagnosed adults and children in Sao Paulo, Brazil. AIDS Res Hum Retroviruses 2015; 31(12): 1219-24.
[http://dx.doi.org/10.1089/aid.2014.0354] [PMID: 25826640]
[65]
Ferreira FG, Pinto JA, Kakehasi FM, et al. Prevalence of primary drug resistance-associated mutations among HIV type 1 vertically Infected children in Belo Horizonte, Brazil. AIDS Res Hum Retroviruses 2010; 26(2): 229-32.
[http://dx.doi.org/10.1089/aid.2009.0146] [PMID: 20156105]
[66]
Soto-Ramirez LE, Rodriguez-Diaz R, Harris DR, Hazra R. HIV drug resistance-associated mutations in antiretroviral naïve HIV-1-infected Latin American children. ances in virology 2010; 1-5.
[67]
Bure D, Makhdoomi MA, Lodha R, et al. Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naïve and treated pediatric patients. Viruses 2015; 7(2): 590-603.
[http://dx.doi.org/10.3390/v7020590] [PMID: 25674767]
[68]
Sehgal S, Pasricha N, Singh S. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome. Indian J Med Microbiol 2008; 26(4): 372-4.
[http://dx.doi.org/10.4103/0255-0857.43583] [PMID: 18974494]
[69]
Silverman RA, John-Stewart GC, Beck IA, et al. Predictors of mortality within the first year of initiating antiretroviral therapy in urban and rural Kenya: A prospective cohort study. PLoS One 2019; 14(10) e0223411
[http://dx.doi.org/10.1371/journal.pone.0223411] [PMID: 31584992]
[70]
Sylla M, Dolo O, Maiga AI, Traore FT, Coulibaly YA, Togo J, et al. Second-line antiretroviral therapy failure and characterization of HIV-1 drug resistance patterns in children in Mali. Arch Pediatr 2019; 26(5): 254-8.
[71]
Memarnejadian A, Gouklani H, Mohammadi S, Moosazadeh M, Choi J. Prevalence of HIV-1 pre-treatment drug resistance in a southern province of Iran, 2016-2017. Arch Virol 2018; 163(1): 57-63.
[http://dx.doi.org/10.1007/s00705-017-3572-1] [PMID: 28983848]
[72]
Mohraz M, Tayeri K, Tabar HN, Jozani ZB, Sadeghi L. Evaluation of Acquired HIV Drug Resistance among People Living with HIV Who Have Taken Antiretroviral Therapy for 9-15 Months in 14 Triangular Clinics in Iran, 2015-2016. Intervirology 2019; 1-9.
[PMID: 30861512]
[73]
Farrokhi M, Moallemi S, Shirkoohi R, et al. Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in Tehran, Iran. Iran J Public Health 2017; 46(9): 1256-64.
[PMID: 29026792]
[74]
Golmohammadi R, Baesi K, Moradi A, Farrokhi M, McFarland W, Parsamajd S. The First Characterization of HIV-1 Subtypes and Drug Resistance Mutations among Antiretrovirally Treated Patients in Kermanshah, Iran. Intervirology 2017; 60(1-2): 33-7.
[http://dx.doi.org/10.1159/000478701] [PMID: 28795954]
[75]
Davarpanah MA, Motazedian N, Joulaei H, Aghasadeghi MR, Faramarzi H, Aghah E. Comparison of antiretroviral drug resistance among treatment-naive and treated HIV-infected individuals in Shiraz, Iran. Arch Virol 2018; 163(1): 99-104.
[http://dx.doi.org/10.1007/s00705-017-3549-0] [PMID: 28986714]