J. Pharm. Pharmacogn. Res., vol. 13, no. 5, pp. 1502-1510, Sep-Oct 2025.
DOI: https://doi.org/10.56499/jppres25.2494_13.5.1502
Original Article
Redox status alterations in Cuban HIV patients: The impact of aging and antiretroviral therapy
[Alteraciones del estado redox en pacientes cubanos con VIH: Impacto de la terapia antirretroviral y el envejecimiento]
Lizette Gil-del-Valle1*, Daymé Hernández-Requejo1, Jessica Rodríguez-Pérez1, Yusimit Bermúdez-Alfonso1, María C. Hernández-González-Abreu 1, Teresa Rosell-Guerra1, Yaumara Ugarte-Pérez1, Odalys Calderón-Fuentes1, María C. Godines-López1, Leidys García Vichot1, Yelena Gayoso-Fernández1, L. Jorge Pérez-Ávila1, Alejandro Ardiles-Rivera2, Gabino Garrido3
1Instituto “Pedro Kourí” (IPK), La Habana, Cuba.
2Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomás, Antofagasta, Chile.
3Departamento de Ciencias Farmacéuticas, Universidad Católica del Norte, Angamos 061, Antofagasta, Chile.
*E-mail: lgil@ipk.sld.cu
Abstract
Context: Pro-oxidant mechanisms play a critical role in the pathogenesis of HIV infection, and both antiretroviral therapy (ART) and aging have been implicated in exacerbating systemic oxidative stress.
Aims: To characterize plasma redox status in HIV-infected Cuban patients receiving ART, with comparisons between individuals younger and older than 50 years of age, as well as with age- and sex-matched HIV-negative controls.
Methods: A case–control study was conducted involving 120 participants divided into four groups: HIV-positive patients aged <50 and ≥50 years, and HIV-negative controls in the same age ranges. Biomarkers of oxidative stress, hematological and biochemical parameters, and markers of HIV progression were evaluated using standardized assays.
Results: HIV-positive individuals exhibited significantly elevated markers of oxidative damage and altered antioxidant responses compared to controls (p < 0.05), with more pronounced imbalances observed in the ≥50 age group. Among HIV-positive participants over 50, 66% demonstrated simultaneous alterations across multiple redox biomarkers. No significant correlations were found between oxidative stress indicators and CD4⁺ T-cell counts, viral load, or other clinical parameters (p > 0.05), which remained within normal reference ranges across all groups.
Conclusions: Aged HIV-infected patients under ART showed marked redox imbalance, suggesting reduced antioxidant capacity and increased oxidative damage. These findings support the inclusion of redox monitoring as a component of clinical assessment in older individuals living with HIV.
Keywords: aging; antioxidant defense; antiretroviral therapy; HIV infection; oxidative stress; redox status.

Resumen
Contexto: Los mecanismos prooxidantes influyen de manera crítica en la patogénesis de la infección VIH, en la que el uso de los antirretrovirales y el envejecimiento han sido implicados exacerbando el estrés oxidativo sistémico.
Objetivos: Caracterizar el estado de oxidación reducción plasmático de pacientes cubanos VIH menores y mayores de 50 años tratados con antirretrovirales y compararlos con grupos controles relacionados en edad y sexo.
Métodos: Se realizó un estudio de casos y controles, con simple cegamiento por los analistas del laboratorio, con 120 personas distribuidas en cuatro grupos: pacientes VIH (casos-mayores y menores 50 años) e individuos seronegativos al VIH (grupo control-mayores y menores de 50 años). Se evaluaron biomarcadores de estrés oxidativo, hematológicos, hemoquímicos y de progresión de la infección.
Resultados: Los grupos VIH con respecto a los controles presentaron diferencias significativas en los índices de daño oxidativo y de respuesta antioxidante (p<0,05) en todos los parámetros redox. Los individuos VIH mayores de 50 años con respecto a los menores de 50 años presentaron diferencias significativas (p<0,05) en los parámetros redox. La variación simultánea de los indicadores redox se observó en el 66% de los individuos VIH mayores de 50 años. Sin correlación entre los biomarcadores de estrés oxidativo, carga viral, linfocitos T CD4+, hematológicos y hemoquímicos (p>0,05), estos últimos no mostraron diferencias entre grupos y estuvieron en el intervalo de referencia normal.
Conclusiones: Se evidenció menor capacidad antioxidante y daño oxidativo mayor en pacientes VIH mayores de 50 años. La evaluación y modulación del estado de oxidación reducción, debe ser valorada como estrategia de análisis integral para el seguimiento y tratamiento complementario de estos pacientes.
Palabras Clave: antirretrovirales; defensa antioxidante; edad; estado redox; estrés oxidativo; infección VIH; terapia antirretroviral.

Citation Format: Gil del Valle L, Hernández Requejo D, Rodríguez Pérez J, Bermudez-Alfonso Y, Hernández Gonzalez-Abreu MC, Ugarte Y, Calderon O, Godinez MC, Garcia-Vichot L, Rosell Guerra T, Gayoso Fernández Y, Perez Ávila LJ, Ardiles-Rivera A, Garrido G (2025) Redox status alterations in Cuban HIV patients: The impact of aging and antiretroviral therapy. J Pharm Pharmacogn Res 13(5): 1502–1510. https://doi.org/10.56499/jppres25.2494_13.5.1502
References
Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL (2009) Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 390(3): 191-214. https://doi.org/10.1515/BC.2009.033
Boyd AT, Oboho I, Paulin H, Ali H, Godfrey C, Date A, Cavanaugh J (2020) Addressing advanced HIV disease and mortality in global HIV programming. AIDS research and therapy 17: 40. https://doi.org/10.1186/s12981-020-00296-x
Clairborne A (1986) Catalase activity. In: Green-Wald R, editor. Handbook of Methods for Oxygen Radical Research. Boca Ratón: CRC Press, p. 283-284.
Curieses Andrés CM, Pérez de la Lastra JM, Andrés Juan C, Plou FJ, Pérez‐Lebeña E (2023) From reactive species to disease development: Effect of oxidants and antioxidants on the cellular biomarkers. J Biochem Mol Toxicol 37(11): e23455. https://doi.org/10.1002/jbt.23455
Deavall DG, Martin EA, Horner JM, Roberts R (2012) Drug-induced oxidative stress and toxicity. J Toxicol 2012: 645460. https://doi.org/10.1155/2012/645460
Deeks SG, Phillips AN (2009) HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 338: a3172. https://doi.org/10.1136/bmj.a3172
Erdelmeier I, Gérard-Monnier D, Yadan JC, Chaudière J (1998) Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem Res Toxicol 11(10): 1184-1194. https://doi.org/10.1021/tx970180z
González-Blanco I, Rosell-Guerra T, Gravier-Hernández R, Pérez Correa D, Hernández-Requejo D, León-Fernández OS, Pérez-Ávila LJ, Gil-del Valle L (2018) Hematologic, biochemical, virologic and immunological status of Cuban HIV patients treated with four generic antiretroviral combinations during two years. SciFed J AIDS HIV Res 2(1): 30-40.
Gravier R, González I, Pérez D, Hernández D, Bermúdez Y, Gil L, León OS, Pérez J (2014) Redox indexes and progression markers in HIV-infected patients treated during six months with three different HAART combinations. Oxid Antioxid Med Sci 3(3): 201-209. https://doi.org/10.5455/oams.170914.or.074
Harshithkumar R, Shah P, Jadaun P, Mukherjee A (2024) ROS chronicles in HIV infection: genesis of oxidative stress, associated pathologies, and therapeutic strategies. Curr Issues Mol Biol 46(8): 8852-8873. https://doi.org/10.3390/cimb46080523
Hernández-Reyes LH (2013) Advances and clinical application of automated hematic cytometry. Rev Cubana Hematol Inmunol Hemoter 29(1): 24-39.
Lee C (2018) Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid Med Cell Longev 2018: 6208067. https://doi.org/10.1155/2018/6208067
Lin N, Erdos T, Louie C, Desai R, Lin N, Ayzenberg G, Venketaraman V (2024) The role of glutathione in the management of cell-mediated immune responses in individuals with HIV. Int J Mol Sci 25(5): 2952. https://doi.org/10.3390/ijms25052952
Lopera-Rodríguez JA, López-Quiceno L (2021) Lipid profile and integrase inhibitors: a systematic review and metaanalysis. CES Med 35(2): 77-97. https://doi.org/10.21615/cesmedicina.6017
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47(3): 469-474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
Marrocco I, Altieri F, Peluso I (2017) Measurement and clinical significance of biomarkers of oxidative stress in humans. Oxid Med Cell Longev 2017: 6501046. https://doi.org/10.1155/2017/6501046
McLemore JL, Beeley P, Thorton K, Morrisroe K, Blackwell W, Dasgupta A (1998) Rapid automated determination of lipid hydroperoxide concentrations and total antioxidant status of serum samples from patients infected with HIV: Elevated lipid hydroperoxide concentrations and depleted total antioxidant capacity of serum samples. Am J Clin Pathol 109(3): 268-273. https://doi.org/10.1093/ajcp/109.3.268
Mendez OF, Pérez Chacón D, Baly Gil A, Pérez Ávila J (2022) Response and adherence to antiretroviral treatment in people over 50 years of age living with HIV/AIDS. Rev Cuba Hig Epidemiol 59: e1321.
MINSAP (2023) Anuario Estadístico de Salud. Cuba: Ministerio de Salud Pública. https://temas.sld.cu/estadisticassalud/2024/09/30/anuario-estadistico-de-salud-2023/ [Consulted 22 January, 2025].
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20(7): 1126-1167. https://doi.org/10.1089/ars.2012.5149
Muralidharan S, Mandrekar P (2013) Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 94(6): 1167-1184. https://doi.org/10.1189/jlb.0313153
Özdemirler G, Mehmetcik G, Öztezcan S, Toker G, Sivas A, Uysal M (1995) Peroxidation potential and antioxidant activity of serum in patients with diabetes mellitus and myocard infarction. Horm Metab Res 27(4): 194-196. https://doi.org/10.1055/s-2007-979938
Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30(1): 11-26. https://doi.org/10.1007/s12291-014-0446-0
Rodriguez NR, Fortune T, Hegde E, Weinstein MP, Keane AM, Mangold JF, Swartz TH (2024) Oxidative phosphorylation in HIV-1 infection: impacts on cellular metabolism and immune function. Front Immunol 15: 1360342. https://doi.org/10.3389/fimmu.2024.1360342
Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24(10): R453-R462. https://doi.org/10.1016/j.cub.2014.03.034
Shytaj IL, Lucic B, Forcato M, Penzo C, Billingsley J, Laketa V, Bosinger S, Stanic M, Gregoretti F, Antonelli L, Oliva G, Frese CK, Trifunovic G, Eibl C, Silvestri G, Bicciato S, Savarino A, Lusic M (2020) Alterations of redox and iron metabolism accompany the development of HIV latency. EMBO J 39(9): e102209. https://doi.org/10.15252/embj.2019102209
Sies H, Jones DP (2020) Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 21(7): 363-383. https://doi.org/10.1038/s41580-020-0230-3
Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal Biochem 27(3): 502-522. https://doi.org/10.1016/0003-2697(69)90064-5
UNAIDS (2024) Global HIV & AIDS statistics — Fact sheet 2024. Global HIV statistics. https://www.unaids.org/es/resources/fact-sheet [Consulted 23 December, 2024].
Valero-Cedeño NJ, Veliz-Castro TI, Merchán-Villafuerte KM, Vargas-López JM, Murillo-Suárez A, Velastegui-Mendoza MA (2020) Alteration of biochemical parameters in patients with HIV/AIDS: how much does antiretroviral therapy provide? Dom Cien 6(1): 292-308. http://dx.doi.org/10.23857/dc.v5i1.1041
WHO (2017) WHO Prequalification of Diagnostics Programme. Public Report. Product: NucliSENS EasyQ® HIV-1 v2.0 (Automated). Number: PQDx 0127-0. https://extranet.who.int/prequal/sites/default/files/whopr_files/PQDx_0127-016-00_NucliSENS-EasyQ-HIV-1_v1.pdf [Consulted 20 December, 2024].
Witko-Sarsat V, Friedlander M, Nguyen Khoa T, Capeillère-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drüeke T, Descamps-Latscha B (1998) Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 161(5): 2524-2532.
© 2025 Journal of Pharmacy & Pharmacognosy Research