Abstract
HIV-1 transmitted drug resistance (TDR) occurs when primary viruses bear drug resistance mutations (DRMs). TDR causes first-line antiretroviral (ARV) therapy (ART) failure and is becoming more pronounced due to the widespread use of ART. With the absence of routine individual-level drug resistance testing, the World Health Organization (WHO) recommends the tracking of TDR mutations and optimizing the first-line ART following pre-treatment drug resistance (PDR) surveys. Here, we report the PDR frequency for the first time in Hormozgan, a southern province of Iran. In this study, 41 blood samples from HIV-1-positive ART-candidate volunteers were collected across the province between April 2016 and March 2017. Phylogenetic analysis of the sequenced protease (PR) and reverse transcriptase (RT) regions showed that 39 out of 41 samples (95%) were CRF35_AD and the two remaining cases were subtype B (2.5%) and C (2.5%). D67G (2.4%), a mutation that reduces susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs) was the only detectable TDR mutation in this population. Two other DRMs, including E138A (9.7%) and V179T (4.9%), which confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), were also identified. Although no major protease inhibitor (PI) resistance mutations were detected, the minor mutations L10F and L33F (2.5% each) as well as several highly frequent polymorphic mutations were identified. Our results show a PDR frequency of 17% in infected individuals from Hormozgan, classified further as 2.4% NRTIs and 14.6% NNRTIs. These results suggest that first-line ART should be practiced carefully in Hormozgan province, and alternative regimens may become necessary for all starters.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Clutter DS, Jordan MR, Bertagnolio S, Shafer RW (2016) HIV-1 drug resistance and resistance testing. Infect Genet Evol 46:292–307
Lai CC, Liu WC, Fang CT, Yang JY, Chang LH, Wu PY, Luo YZ, Chang SF, Su YC, Chang SY, Hung CC (2016) Transmitted drug resistance of HIV-1 strains among individuals attending voluntary counselling and testing in Taiwan. J Antimicrob Chemother 71:226–234
World Health Organization (2016) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach, 2nd edn. Geneva, Switzerland. http://www.who.int/hiv/pub/arv/arv-2016/en/. Accessed 10 Feb 2017
Phillips AN, Cambiano V, Miners A, Revill P, Pillay D, Lundgren JD, Bennett D, Raizes E, Nakagawa F, De Luca A, Vitoria M, Barcarolo J, Perriens J, Jordan MR, Bertagnolio S (2014) Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis. Lancet HIV 1:e85–e93
Myers JE, Taylor BS, Rojas Fermin RA, Reyes EV, Vaughan C, Jose L, Javier C, Franco Estevez R, Donastorg Cabral Y, Batista A, Lie Y, Coakley E, Hammer SM, Brudney K (2012) Transmitted drug resistance among antiretroviral-naive patients with established HIV type 1 infection in Santo Domingo, Dominican Republic and review of the Latin American and Caribbean literature. AIDS Res Hum Retroviruses 28:667–674
Bennett DE, Myatt M, Bertagnolio S, Sutherland D, Gilks CF (2008) Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment. Antivir Ther 13(Suppl 2):25–36
World Health Organization (2014) Concept note: surveillance of HIV drug resistance in adults initiating antiretroviral therapy (pre-treatment HIV drug resistance) HIV/AIDS. Geneva, Switzerland. http://www.who.int/hiv/pub/drugresistance/pretreatment_drugresistance/en/. Accessed 10 Feb 2017
Kamarulzaman A (2013) Fighting the HIV epidemic in the Islamic world. Lancet 381:2058–2060
National AIDS Committee Secretariat Ministry of Health and Medical Education (2015) Islamic Republic of Iran AIDS progress report on monitoring of the United Nations General Assembly Special Session on HIV and AIDS
Baesi K, Ravanshad M, Ghanbarisafari M, Saberfar E, Seyedalinaghi S, Volk JE (2014) Antiretroviral drug resistance among antiretroviral-naive and treatment experienced patients infected with HIV in Iran. J Med Virol 86:1093–1098
Farrokhi M, Moallemi S, Baesi K, Ahsani-Nasab S, Gholami M, Sadeghi L, Mohraz M (2016) HIV drug resistance and phylogeny profile in naive and antiretroviral-experienced patients in Tehran, Iran. Intervirology 59:131–136
Hamkar R, Mohraz M, Lorestani S, Aghakhani A, Truong HH, McFarland W, Banifazl M, Eslamifar A, Foroughi M, Pakfetrat A, Ramezani A (2010) Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients. AIDS 24(Suppl 2):S85–S91
Jahanbakhsh F, Hattori J, Matsuda M, Ibe S, Monavari SH, Memarnejadian A, Aghasadeghi MR, Mostafavi E, Mohraz M, Jabbari H, Kamali K, Keyvani H, Azadmanesh K, Sugiura W (2013) Prevalence of transmitted HIV drug resistance in Iran between 2010 and 2011. PLoS One 8:e61864
Memarnejadian A, Menbari S, Mansouri SA, Sadeghi L, Vahabpour R, Aghasadeghi MR, Mostafavi E, Abdi M (2015) Transmitted drug resistance mutations in antiretroviral-naive injection drug users with chronic HIV-1 infection in Iran. PLoS One 10:e0126955
Naziri H, Baesi K, Moradi A, Aghasadeghi MR, Tabarraei A, McFarland W, Davarpanah MA (2016) Antiretroviral drug resistance mutations in naive and experienced patients in Shiraz, Iran, 2014. Arch Virol 161:2503–2509
Vahabpour R, Bokharaei-Salim F, Kalantari S, Garshasbi S, Monavari SH, Esghaei M, Memarnejadian A, Fakhim A, Keyvani H (2017) HIV-1 genetic diversity and transmitted drug resistance frequency among Iranian treatment-naive, sexually infected individuals. Arch Virol 162:1477–1485
World Health Organization (2015) HIV Drug resistance surveillance guidance. Geneva, Switzerland http://www.who.int/hiv/pub/drugresistance/hiv-drug-resistance-2015-update/en/. Accessed 10 Feb 2017
Sugiura W, Matsuda M, Abumi H, Yamada K, Taki M, Ishikawa M, Miura T, Fukutake K, Gouchi K, Ajisawa A, Iwamoto A, Hanabusa H, Mimaya J, Takamatsu J, Takada N, Kakishita E, Yoshioka A, Kashiwagi S, Shirahata A, Nagai Y (1999) Prevalence of drug resistance-related mutations among HIV-1s in Japan. Jpn J Infect Dis 52:21–22
Bennett DE, Camacho RJ, Otelea D, Kuritzkes DR, Fleury H, Kiuchi M, Heneine W, Kantor R, Jordan MR, Schapiro JM, Vandamme AM, Sandstrom P, Boucher CA, van de Vijver D, Rhee SY, Liu TF, Pillay D, Shafer RW (2009) Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One 4:e4724
Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 30:2725–2729
Pineda-Pena AC, Faria NR, Imbrechts S, Libin P, Abecasis AB, Deforche K, Gomez-Lopez A, Camacho RJ, de Oliveira T, Vandamme AM (2013) Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools. Infect Genet Evol 19:337–348
Castro H, Pillay D, Cane P, Asboe D, Cambiano V, Phillips A, Dunn DT, Resistance UKCGoHD (2013) Persistence of HIV-1 transmitted drug resistance mutations. J Infect Dis 208:1459–1463
Rimsky L, Vingerhoets J, Van Eygen V, Eron J, Clotet B, Hoogstoel A, Boven K, Picchio G (2012) Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. J Acquir Immune Defic Syndr 59:39–46
Melikian GL, Rhee SY, Varghese V, Porter D, White K, Taylor J, Towner W, Troia P, Burack J, Dejesus E, Robbins GK, Razzeca K, Kagan R, Liu TF, Fessel WJ, Israelski D, Shafer RW (2014) Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother 69:12–20
Rhee SY, Taylor J, Fessel WJ, Kaufman D, Towner W, Troia P, Ruane P, Hellinger J, Shirvani V, Zolopa A, Shafer RW (2010) HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother 54:4253–4261
Phillips A, Cambiano V, Nakagawa F, Mabugu T, Miners A, Ford D, Pillay D, De Luca A, Lundgren J, Revill P (2014) Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings. PLoS One 9:e109148
Mousavi SM, Hamkar R, Gouya MM, Safaie A, Zahraei SM, Yazdani Z, Asbaghi Namini S, Bertagnolio S, Sutherland D, Sandstrom P, Brooks J (2010) Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study. Arch Virol 155:329–334
Tang MW, Shafer RW (2012) HIV-1 antiretroviral resistance: scientific principles and clinical applications. Drugs 72:e1–25
Soheilli ZS, Ataiee Z, Tootian S, Zadsar M, Amini S, Abadi K, Jauvin V, Pinson P, Fleury HJ, Samiei S (2009) Presence of HIV-1 CRF35_AD in Iran. AIDS Res Hum Retroviruses 25:123–124
Acknowledgements
The authors would like to thank all employees of the counseling and behavioral centers (triangular clinics) and the Combating Infectious Diseases Group, Hormozgan University of Medical Sciences, for their help in sample collection. We also thank Drs. Sedaghat and Davoodian for their consultation, and Mehrnoosh Bashirzadeh for her help in the experiments. This work was financially supported by the Research Deputy of Hormozgan University of Medical Sciences, Iran.
Author information
Authors and Affiliations
Corresponding author
Additional information
Handling Editor: Li Wu.
Rights and permissions
About this article
Cite this article
Memarnejadian, A., Gouklani, H., Mohammadi, S. et al. Prevalence of HIV-1 pre-treatment drug resistance in a southern province of Iran, 2016-2017. Arch Virol 163, 57–63 (2018). https://doi.org/10.1007/s00705-017-3572-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00705-017-3572-1