Pharmacogenetics of HIV therapy: State of the art in Latin American countries

Velozo, Camila de Almeida; Lamarão, Flávia Rachel Moreira; Alvarado-Arnez, Lucia Elena; Cardoso, Cynthia Chester

doi:10.1590/1678-4685-GMB-2022-0120

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Genetics and Molecular Biology

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Sumário

Young Brazilian Geneticists - Special Issue • Genet. Mol. Biol. 45 (3 Suppl 1) • 2022 • https://doi.org/10.1590/1678-4685-GMB-2022-0120 copy

Pharmacogenetics of HIV therapy: State of the art in Latin American countries

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The use of combined antiretroviral therapy (cART) has resulted in a remarkable reduction in morbidity and mortality of people living with HIV worldwide. Nevertheless, interindividual variations in drug response often impose a challenge to cART effectiveness. Although personalized therapeutic regimens may help overcome incidence of adverse reactions and therapeutic failure attributed to host factors, pharmacogenetic studies are often restricted to a few populations. Latin American countries accounted for 2.1 million people living with HIV and 1.4 million undergoing cART in 2020-21. The present review describes the state of art of HIV pharmacogenetics in this region and highlights that such analyses remain to be given the required relevance. A broad analysis of pharmacogenetic markers in Latin America could not only provide a better understanding of genetic structure of these populations, but might also be crucial to develop more informative dosing algorithms, applicable to non-European populations.

Keywords:
HIV; Latin America; pharmacogenetics; CYP2B6; HLA-B*57:01

Gene	Outcome	Population	Reference
Metabolism enzymes
CYP2B6	Higher efavirenz levels	Haiti	*Leger et al., 2009*Leger P, Dillingham R, Beauharnais CA, Kashuba ADM, Rezk NL, Fitzgerald DW, Pape JW and Haas DW (2009) CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in port-au-prince Haiti. J Infect Dis 200:955-964.
	Higher efavirenz levels	Chile	*Carr et al., 2010Carr DF, la Porte CJL, Pirmohamed M, Owen A and Cortes CP (2010) Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort. J Antimicrob Chemother 65:1889-1893.; Cortes et al., 2013*Cortes CP, Siccardi M, Chaikan A, Owen A, Zhang G and Porte CJLL (2013) Correlates of efavirenz exposure in chilean patients affected with human immunodeficiency virus reveals a novel association with a polymorphism in the constitutive androstane receptor. Ther Drug Monit 35:78-83.
	Lower CD4 T cell counts	Brazil	*Queiroz et al., 2017*Queiroz MAF, Laurentino RV, da Silva Graça Amoras E, Araújo MSM de, Gomes STM, Lima SS, Vallinoto ACR, de Oliveira Guimarães Ishak M, Ishak R and Machado LFA (2017) The CYP2B6 G516T polymorphism influences CD4+ T-cell counts in HIV-positive patients receiving antiretroviral therapy in an ethnically diverse region of the Amazon. Int J Infect Dis 55:4-10.
	Adverse effects to efavirenz	Brazil	de Almeidaet al., 2018de Almeida TB, de Azevedo MCVM, Pinto JFDC, Ferry FRA, da Silva GAR, de Castro IJ, Baker P, Tanuri A, Haas DW and Cardoso CC (2018). Drug metabolism and transport gene polymorphisms and efavirenz adverse effects in Brazilian HIVpositive individuals. J Antimicrob Chemother 73:2460-2467.
	CNS adverse effects to efavirenz	Chile	*Poblete et al., 2021Poblete D, Bernal F, Llull G, Archiles S, Vasquez P, Chanqueo L, Soto N, Lavanderos MA, Quiñones LA and Varela NM (2021) Pharmacogenetic associations between atazanavir/UGT1A128 and efavirenz/rs3745274 (CYP2B6) account for specific adverse reactions in Chilean patients undergoing antiretroviral therapy. Front Pharmacol 12:660965.
NRI12 and NR1I3	Virological response	Brazil	*de Almeida Velozo et al., 2021*de Almeida Velozo C, de Almeida TB, de Azevedo MCVM, Espasandin I, da Cunha Pinto JF, López S, Pizzatti L, Tanuri A, da Silva Santos S, Ribeiro-Alves M et al. (2021). Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals. Pharmacogenomics J 1:33-38.
NR1I3	Efavirenz exposure	Chile	*Cortes et al., 2013*Cortes CP, Siccardi M, Chaikan A, Owen A, Zhang G and Porte CJLL (2013) Correlates of efavirenz exposure in chilean patients affected with human immunodeficiency virus reveals a novel association with a polymorphism in the constitutive androstane receptor. Ther Drug Monit 35:78-83.
UGT1A1	Atazanavir related hyperbilirubinemia	Brazil	*Turatti et al., 2012Turatti L, Sprinz E, Lazzaretti RK, Kuhmmer R, Agnes G, Silveira JM, Basso RP, Pinheiro C a T, Silveira MF, de Almeida S et al. (2012) Short communication: UGT1A128 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in southern Brazil. AIDS Res Hum Retroviruses 28:1015-1018.
UGT1A1	Atazanavir related hyperbilirubinemia	Chile	*Poblete et al., 2021Poblete D, Bernal F, Llull G, Archiles S, Vasquez P, Chanqueo L, Soto N, Lavanderos MA, Quiñones LA and Varela NM (2021) Pharmacogenetic associations between atazanavir/UGT1A128 and efavirenz/rs3745274 (CYP2B6) account for specific adverse reactions in Chilean patients undergoing antiretroviral therapy. Front Pharmacol 12:660965.
Drug transporters
ABCB1	Lopinavir plasma levels	Argentina	*Bellusci et al., 2013*Bellusci CP, Rocco C, Aulicino P, Mecikovsky D, Curras V, Hegoburu S, Bramuglia GF, Bologna R, Sen L and Mangano A (2013) Influence of MDR1 C1236T polymorphism on lopinavir plasma concentration and virological response in HIV-1-infected children. Gene 522:96-101.
	Virological failure of PI containing regimens	Brazil	*Coelho et al., 2013*Coelho AV, Silva SP, de Alencar LC, Stocco G, Crovella S, Brandão LA and Guimarães RL (2013) ABCB1 and ABCC1 variants associated with virological failure of first-line protease inhibitors antiretroviral regimens in Northeast Brazil patients. J Clin Pharmacol 53:1286-93.
	Decreased immunological response to efavirenz	Brazil	*Coelho et al., 2018*Coelho AVC, Moura RR de, Guimarães RL, Brandão LAC and Crovella S (2018) Antiretroviral therapy immunologic non-response in a Brazilian population: Association study using pharmaco- and immunogenetic markers. Brazilian J Infect Dis 22:392-401.
ABCC1	Virological failure of PI containing regimens	Brazil	*Coelho et al., 2013*Coelho AV, Silva SP, de Alencar LC, Stocco G, Crovella S, Brandão LA and Guimarães RL (2013) ABCB1 and ABCC1 variants associated with virological failure of first-line protease inhibitors antiretroviral regimens in Northeast Brazil patients. J Clin Pharmacol 53:1286-93.
ABCC2	Intolerance to PI containing regimens	Brazil	*Arruda et al., 2016*Arruda MB, Campagnari F, De Almeida TB, Couto-Fernandez JC, Tanuri A and Cardoso CC (2016) Single nucleotide polymorphisms in cellular drug transporters are associated with intolerance to antiretroviral therapy in brazilian HIV-1 positive individuals. PLoS One 11:e0163170.
SLCO1B1	Trough plasma concentration of lopinavir	Brazil	*Kohlrausch et al., 2010*Kohlrausch FB, De Cássia Estrela R, Barroso PF and Suarez-Kurtz G (2010) The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men. Br J Clin Pharmacol 69:95-98.
SLCO1B1	Intolerance to NRTIs	Brazil	*Arruda et al., 2016*Arruda MB, Campagnari F, De Almeida TB, Couto-Fernandez JC, Tanuri A and Cardoso CC (2016) Single nucleotide polymorphisms in cellular drug transporters are associated with intolerance to antiretroviral therapy in brazilian HIV-1 positive individuals. PLoS One 11:e0163170.

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[1] Send correspondence to
Cynthia Chester Cardoso. Universidade Federal do Rio de Janeiro, Instituto de Biologia, Laboratório de Virologia Molecular, Av. Carlos Chagas Filho, 373, CCS, Bloco A, Sala 121, 21941-902, Ilha do Fundão, RJ, Brazil. E-mail: cynthiac@biologia.ufrj.br.